Amr Thesis Merged

A RETROSPECTIVE STUDY ON BACTERIAL INFECTIONS,
ANTIMICROBIAL RESISTANCE PATTERNS AND

UTILIZATION OF ANTIBIOTIC THERAPY IN A TERTIARY
CARE HOSPITAL.
DISSERTATION
SUBMITTED TO THE OSMANIA UNIVERSITY, HYDERABAD

IN PARTIAL FULFILLMENT OF THE REQUIREMENT
FOR THE AWARD OF THE DEGREE OF
DOCTOR OF PHARMACY
SUBMITTED BY
Pharm. D Vth year students
Alle Poojitha 170115882011
V. Bindu Madhavi 170115882010
N. Hanisha Gupta 170115882004
QamarUnnisa Begum Siddiqui 170115882028
UNDER THE GUIDANCE OF

Mrs. Gouhar Sultana, M.Pharm
Assistant Professor, Dept. of Pharmacy Practice.
G. PULLA REDDY COLLEGE OF PHARMACY

HYDERABAD - 500 028 (TS)
SEPTEMBER 2020
DECLARATION
We Alle Poojitha, V.Bindu Madhavi, N.Hanisha Gupta, QamarUnnisa Begum Siddiqui, Students
of Pharm.D bearing the H.T No. 170115882011, 170115882010, 170115882004 and
170115882028 respectively, Department of Pharmacy Practice, G. Pulla Reddy College of
Pharmacy, Osmania University, Hyderabad hereby declare that the work embodied in this
dissertation entitled “A Retrospective Study On Bacterial Infections, Antimicrobial
Resistance Patterns And Utilization Of Antibiotic Therapy In A Tertiary Care Hospital”, is
submitted to Osmania University for the partial fulfilment of the requirements for the award of
degree of Doctor of Pharmacy in Pharmacy Practice under faculty of Pharmacy is the original
research work carried out by us under the guidance and supervision Mrs. Gouhar Sultana,
M.Pharm, Department of Pharmacy Practice, G. Pulla Reddy College of Pharmacy.
Further we hereby declare and inform that the contents presented in this thesis has not been
submitted by me for the award of any other degree or diploma of this or any other University.
PLACE:
DATE:
ALLE POOJITHA
V. BINDU MADHAVI
N. HANISHA GUPTA
QAMARUNNISA BEGUM SIDDIQUI

CERTIFICATE
This is to certify that the dissertation entitled “A Retrospective Study On Bacterial Infections,
Antimicrobial Resistance Patterns And Utilization Of Antibiotic Therapy In A Tertiary
Care Hospital”, is submitted to Osmania University for the partial fulfillment of requirements
for the award of degree of Doctor of Pharmacy in Pharmacy Practice under Faculty of
Pharmacy embodies the results and studies of a bonafide research work of Ms. Alle Poojitha,
Ms. V. Bindu Madhavi, Ms. N. Hanisha Gupta, Ms. QamarUnnisa Begum Siddiqui under
the supervision of Mrs. Gouhar Sultana, at G. Pulla Reddy College of Pharmacyand
thecontents of the thesis do not form the basis for the award of any other degree ordiploma to the
candidates from this or any other university elsewhere.
Prof. Dr. B. Madhava Reddy

Principal
G. Pulla Reddy College of Pharmacy
Hyderabad
CERTIFICATE
This is to certify that the dissertation entitled “A Retrospective Study On Bacterial Infections,
Antimicrobial Resistance Patterns And Utilization Of Antibiotic Therapy In A Tertiary
Care Hospital”,is submitted to Osmania University for the partial fulfillment of requirements
for the award of degree of Doctor of Pharmacy in Pharmacy Practice under Faculty of
Pharmacy embodies the results and studies of a bonafide research work of Ms Alle Poojitha,
Ms V.Bindu Madhavi, Ms N.Hanisha Gupta, Ms Qamarunnisa Begum Siddiqui under my
supervision at G. Pulla Reddy College of Pharmacyand thecontents of the thesis do not form the
basis for the award of any other degree ordiploma to the candidates from this or any other
university elsewhere.
Mrs. Gouhar Sultana,

Assistant Professor,
Department of Pharmacy Practice,
G. Pulla Reddy College of Pharmacy,
Hyderabad.
ACKNOWLEDGEMENTS
First and foremost, we would like to thank our parents and all our family members who
have blessed us and instilled in us courage, strength and also the desire to do our best for
achieving our aim.
We wish to express our sincere thanks to Dr. B. Madhava Reddy, Principal and
Professor, G. Pulla Reddy College of Pharmacy, for providing us the best possible
facilities to carry out our work successfully.
We would like to express our sincere gratitude and heartfelt thanks to our Supervisor,
Mrs. Gouhar Sultana, Department of Pharmacy Practice, G. Pulla Reddy College of
Pharmacy for the continuous support to our Doctor of Pharmacy (Pharm.D) study and
research, for her valuable guidance, constant encouragement and patience over the year,
and persistence of these attributes while reading and correcting our thesis. We are thankful
to her for the trust she entrusted on us, which made us to realize our potential.
We would like to express our sincere thanks to Dr. Mustafa Afzal, MBBS, MD, HOD-
Clinical Microbiology and Infection Control; Dr. Mohammed Abuzar Ghufran, Pharm
D., Clinical Pharmacologist; Sudheer Kumar, Biostatistician; Mrs. Jayasree and Mrs.
Manjula, Infection Control department nurses; of Care Hospitals, Nampally, for their
continuous support and encouragement to our Doctor of Pharmacy study and research.
We thank the library faculty of G. Pulla Reddy College of Pharmacy for helping to
make our project work come to fruitful end. Our sincere thanks to all the teaching, non-
teaching and technical staff of G. Pulla Reddy College of Pharmacy who rendered
helping hands in the successful completion of our dissertation.
ALLE POOJITHA
V. BINDU MADHAVI
N. HANISHA GUPTA
QAMARUNNISA BEGUM SIDDIQUI
i
Dedicated to
Our pARENTS
CONTENTS
CONTENTS Page no.

LIST OF TABLES ii
LIST OF FIGURES iii
LIST OF ABBREVIATIONS iv
ABSTRACT vi
1. INTRODUCTION 01
1.1 Definitions 01
1.2 The Discovery Of Antimicrobial Drugs 01
1.3 Classification Of Antibiotics 02
1.4 CDC Classification Of Antibiotic- Resistant Bacterial Infections: 07
Assessment Of Antibacterial Resistance Threats
1.5 Emergence Of AMR 08
1.6 Mechanisms Of Resistance 09
1.7 Global Situation Of AMR 11
1.8 Indian Scenario Of AMR 15
1.9 Factors Causing Antibiotic Resistance 17
1.10 Treatment Guidelines For Infections 22
1.11 Overcoming And Prevention Of Anti-Microbial Resistance 29
2. LITERARUTE REVIEW 33
3. MATERIALS AND METHODS 39
3.1 Objectives Of The Study 39
3.2 Study Design And Methodology 39
3.3 Approval by Institutional Ethics Committee 42
4. RESULTS AND DISCUSSION 43
4.1 RESULTS 43
4.2 DISCUSSION 69
5. CONCLUSION 73
6. APPENDIX
i. Data Collection Form vii
ii. IEC Approval Letter ix
7. REFERENCES 76
CO-CURRICULAR ACTIVITIES 84
LIST OF TABLES
Table TITLE Page

No. No.
1. Classification of Antibiotics 3
2. CDC Assessment of Antibacterial Resistance Threats 8
3. Empiric Treatment Regimens for Urinary Tract Infections 23
4. Standard Doses of Antimicrobial Agents Used In Urinary Tract Infections 24
5. Antimicrobial Choice for Sepsis Condition 25
6. Standard Doses for Antimicrobial Agents Used In Sepsis 26
7. Antimicrobial therapy in URTI 26
8. Choice of Empiric Antimicrobial Therapy In Adult CAP 27
9. Antimicrobial therapy for pediatric CAP 28
10. Drug Doses, Duration and Route of Administration in RTI and CAP 28
11. Sample Selection For Primary Objective 40
12. Sample Selection For Secondary Objective 40
13. Sources of data 41
14. Distribution Of Subjects Based On Age Groups 44
15. Distribution Of Subjects Based On Gender 45
16. Distribution Of Subjects Based On Co-Morbidities 46
17. Distribution Of Subjects Based On Type Of Infections 47
18. Distribution Of Subjects Based On Culture Specimen 48
19. Distribution Of Subjects Based On Organism And Culture Specimen 49
20. Antimicrobial Resistance Patterns Of Gram Negative Bacteria 51
21. Antimicrobial Resistance Patterns Of Gram Positive Bacteria 53
22. Average Number Of Antibiotics Prescribed 54
23. Utilisation Patterns Of Antibiotics Prescribed 55
24. Single Vs Multiple Antibiotic Therapy 57
25. Single Vs Multiple Antibiotic Therapy With Drugs 58
26. Distribution Of MDR Subjects Based On Age Groups 64
27. Distribution Of MDR Subjects Based On Gender 65
28. Etiologies Of Community Acquired MDR Infections 66
29. Antibiotic Susceptibility Patterns For MDR Bacteria 67
ii
LIST OF FIGURES
Figure Title Page

No. No.
1. Bacterial structure and mechanism of action of antibacterial drugs 3
2. Mechanisms of resistance 10
3. Antibiotic Resistance Worldwide Info graphic 14
4. Trends in antibiotic consumption in India, 2000–2015 18
5. Spread of Antibiotic Resistance 22
6. Sample size 43
7. Graphical Representation Of Subjects Based Age Groups 44
8. Graphical Representation of Subjects Based on Gender. 45
9. Graphical Representation of Subjects Based On Comorbidities. 46
10. Graphical Representation of Subjects Based On Type of Infections. 47
11. Graphical Representation of Subjects Based On Type of Culture Specimen 48
12. Graphical Representation For Organisms Isolated from Samples. 50
13. Graphical Representation Of Most Commonly Prescribed Antibiotic 56
Classes.
14. Graphical Representation of Total Number Of Antibiotics Per Prescription 58
15. Graphical Representation For Distribution of MDR Subjects Based On Age 64
Groups.
16. Graphical Representation for Distribution of MDR Subjects Based on 65
Gender.
17. Graphical Representation forOrganisms isolated from MDR samples 66
iii
LIST OF ABBREVIATIONS
AAC N-Acetyl Transferases
ABC ATP-Binding Cassette
AFI Acute Febrile Illness
AcrAB-TolC Multidrug Efflux Pump Subunit Acridine Resistance Protein B
AMR Antimicrobial Resistance
AMOXICLAV Amoxicillin/Clavulanic Acid
ANT Adenylyl Transferases
APH Aminoglycoside Phosphotransferases
APUA The Alliance of Prudent Use of Antibiotics
BAL Broncho-Alveolar Lavage
CAD Coronary Artery Disease
CAP Community Acquired Pneumonia
CAT Chloramphenicol Acetyl Transferases
CA-MRSA Community Acquired MRSA
CDC Centre for Disease Control and Prevention
CONS Coagulase Negative Staphylococcus
Cm1A Chloramphenicol Resistant Gene
C.difficile Clostridium difficile
CKD Chronic Kidney Disease
COPD Chronic Obstructive Pulmonary Disease
CR-GNB Carbapenem Resistant Gram Negative Bacteria
CLSI Clinical And Laboratory Standards Institute
DHF Di hydro Folic Acid
DM Diabetes Mellitus
DNA Deoxy Ribo Nucleic Acid
DMT Drug/Metabolite Transporter
ICU Intensive Care Unit
IV Intra Venous
IM Intra Muscular
iv
MATE Multidrug and Toxic Compound Extension Family
MDR Multidrug Resistance
MF Major Facilitator Family
MIC Minimum Inhibitory Concentration
MRSA Methicillin Resistant Staphylococcus aureus
MYSTIC Meropenem Yearly Susceptibility Test Information Collection
NDM-1 New Delhi Metallo Beta Lactamase
Opr D Outer Membrane Porin D
OD Once daily
OSA Obstructive Sleep Apnea
PABA Para Amino Benzoic Acid
par C DNA Topo-isomerase 4 Subunit A
par E DNA Topo-isomerase 4 Subunit B
PBP Penicillin Binding Protein
PDR Pan Drug Resistance
r RNA Ribosomal Ribonucleic Acid
rpo B RNA Polymerase Beta Subunit
RND Resistance Nodulating Division
Resp. Respiratory
SCC mec Staphylococcal Cassette Chromosome mec
SD Standard Deviation
Spp. Species
t RNA Transfer RNA
Tet Tetracycline Resistant Proteins
THF Tetra hydro Folic Acid
TB Tuberculosis
UTI Urinary Tract Infection
WHO World Health Organization
XDR Extremely Drug Resistant
v
Abstract
ABSTRACT
Aim: Rapidly rising antibiotic resistance is a challenge to comprehensive patient care in all
branches of medical science. Our primary aim is to study the antibiotic resistance patterns of
bacteria and utilization of antibiotics. To study the etiologies of Community acquired MDR
infections.
Methodology: The study duration was six months (August,2019 to January,2020) and data
was collected retrospectively. Antimicrobial resistance pattern testing was done by using
Kirby-Bauer disk diffusion method on Mueller-Hinton agar according to the Clinical and
Laboratory Standards Institute guidelines.
Results: In this study, initially 280 cases were collected, out of which 200 cases were included
in the study based on inclusion and exclusion criteria. Among those cases 186 were gram
negative isolates and 14 were gram positive isolates. E.coli, which is the predominant isolate
among gram negative organisms exhibited a higher resistance to ampicillin followed by
ceftriaxone and cefpodoxime. Among common gram positive isolates, Enterococcus spp. is
mostly resistant to ciprofloxacin followed by levofloxacin and tetracycline. The most
commonly prescribed antibiotic was found to be ceftriaxone followed by
cefoperazone/sulbactam, meropenem, piperacillin/tazobactum, amoxicillin/clavulanate and
clindamycin. Commonly prescribed antibiotic, ceftriaxone which was one the most prevalent
drug against the gram positive bacteria (E. coli, Klebsiella and Enterobacter) has developed
resistance too.
In the present study, 63 community acquired MDR cases were obtained from the nursing
department. E.coli followed by Pseudomonas and Klebsiella were found to be the most
predominant community acquired MDR pathogen.
Conclusion: In our study we have reported the resistance patterns, utilization of antibiotics
and etiologies of community acquired MDR infections. It was observed that frequently isolated
organisms were found to be resistant to most commonly used drugs such as ampicillin,
cefpodoxime, amoxicillin and ceftriaxone which is alarming and calls for a surveillance of
HAIs and community infections to establish the source and transmission pathways.
vi
CHAPTER – 1
INTRODUCTION
CHAPTER 1 INTRODUCTION
1.1 DEFINITIONS:
Antimicrobial resistance:
Antimicrobial resistance occurs when microorganisms (such as bacteria, fungi, viruses, and
parasites) change over time and no longer respond to medicines making infections harder to treat
and increasing the risk of disease spread, severe illness and death. As a result, the medicines
become ineffective and infections persist in the body, increasing the risk of spread to others. 1
Antimicrobials - including antibiotics, antivirals, antifungals and antiparasitics - are medicines

used to prevent and treat infections in humans, animals and plants.
Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-
increasing range of infections caused by bacteria, parasites, viruses and fungi. Microorganisms
that develop antimicrobial resistance are sometimes referred to as “superbugs”.1
Multidrug resistance:
Multidrug resistant (MDR) was defined as acquired non-susceptibility to at least one agent in
three or more antimicrobial categories. 2
1.2 THE DISCOVERY OF ANTIMICROBIAL DRUGS:
In the human history most of bacterial infections were treated using folk medicines and herbal
therapies. In those days treatments were lacking and for some infections there was no treatment
accessible. This increased bacterial contaminations and caused high death rates. The discoveries
by Louis Pasteur and Robert Koch in the late nineteenth century of the existence of micro-
organisms, and the demonstration that they were liable for many infectious diseases including
anthrax and cholera 3 changed the way to deal with treating infectious diseases by providing an
identified cause of disease and target for therapy. In parallel, the ongoing industrial and scientific
revolution in Europe had created a chemical industry with the interest and capability to
manufacture pure chemicals in large volumes. At one of these companies Paul Ehrlich, the
founder of chemotherapy, initiated a search for a chemical ‘magic bullet’ to treat infectious
diseases: a chemical that would selectively kill an infectious microorganism but not harming the
human patient.4 The achievement of that screen brought about the discovery of Salvarsan, an
Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 1

4
arsenic compound which acts against the syphilis spirochete and paved the path for other
compounds or chemicals having antimicrobial properties. The search led to the discovery of the
antibacterial action of sulphonamides, a significant class of synthetic drugs discovered during the
1930s and still being used today.3
A second revolution in antimicrobial treatment started with the discovery of penicillin by

Alexander Fleming in 1928, indicating that organisms themselves could produce antibacterial
substances, so called antibiotics.5 The development of penicillin for clinical use, and its
application during the Second World War, led to an great enthusiasm in searching for other
natural antibiotics. In 1950’s, the use of the whole cell antibacterial screening platform created
by Waksman 6 directed at a variety of fungi and bacteria, led to the “golden age” of antibiotic
discovery. About half of the antibiotic agents known today were discovered during that period.7
Consequently, a great part of the advancement and drug development involved generating
synthetic or semisynthetic derivatives of natural antibiotics, with better pharmacokinetic and
pharmacodynamic properties, and improved spectrum of activity.
Today, the classical distinction between antimicrobials as synthetic molecules and antibiotics as
natural compounds has lost its relevance, since almost all antimicrobials in clinical use have been
structurally modified in the course of development to enhance the antibacterial activity and
reduce their toxic side effects.
The importance of antibiotics in modern medicine can hardly be overstated. In addition to their
critical role in helping to cure a variety of infectious diseases, effective prophylactic antibiotic
therapy supports most of the transplant surgeries and cancer treatments.
1.3 CLASSIFICATION OF ANTIBIOTICS: 8
The antibiotics are classified on the basis of mechanism of action as described in the figure no.1:

Figure 1: Bacterial structure and mechanism of action of antibacterial drugs.

Source: http://tmedweb.tulane.edu/pharmwiki/doku.php/antibiotic_pharmacology
Table 1. Classification Of Antibiotics
DRUG CLASS CLASSIFICATION MECHANISM OF ACTION
1. Acid Resistant Alternative to

penicillin G:
PENICILLINS  Penicillin V. Exerts bactericidal activity via
2.Penicillinase-resistant inhibition of bacterial cell wall
penicillins: synthesis by binding one or
 Methicillin, Cloxacillin, more of the penicillin binding
Dicloxacillin. proteins (PBPs).
3.Extended spectrum penicillins :
a.)Aminopenicillins
 Ampicillin, Bacampicillin,
Amoxicillin.
b.)Carboxypenicillins
 Carbenicillin
c.)Ureidopenicillins
 Piperacillin, Mezlocillin.

CEPHALOSPORINS 1.First generation drugs : Exert bactericidal activity by

 Cefazolin, Cephalexin, interfering with bacterial cell
Cefadroxil wall synthesis and inhibiting
2.Second generation drugs : cross-linking of the
 Cefuroxime, Cefoxitin, peptidoglycan. They are also
Cefaclor, Cefprozil, thought to play a role in the
Cefuroxime axetil. activation of bacterical cell
3.Third generation drugs : autolysins which may
 Cefotaxime, Ceftizoxime, contribute to bacterial cell
Ceftriaxone, Ceftazidime, lysis.
Cefoperazone, Cefixime,
Cefpodoxime proxetil,
Ceftibuten, Ceftamet
pivoxil.
4. Fourth generation drugs:
 Cefepime, Cefpirome.
MONOBACTAMS  Aztreonam Interferes with bactericidal cell

wall synthesis by binding to
and inactivating penicillin-
binding-proteins. This binding
causes the formation of
elongation or bacterial
filamentation resulting in cell
lysis and death.
CARBAPENEMS  Imipenem, Meropenem, Causes rapid bacterial cell

Faropenem, Doripenem. death by covalently binding to
penicillin-binding proteins
(PBPs) involved in the
biosynthesis of mucopeptides
in bacterial cell walls.
BETA-LACTAMASE  Clavulanic Acid, The beta-lactamase inhibitors

INHIBITORS Sulbactam, Tazobactam. are recognized as substrates for
the beta-lactamases produced
by bacteria. This allows the
actual beta-lactams to attack
the bacterial cell wall by
binding to penicillin binding
proteins.

GLYCOPEPTIDES  Vancomycin, Teicoplanin. Vancomycin inhibits

transpeptidation by binding to D-
alanyl-D-alanine residues of the
bacterial cell wall.
Teicoplanin inhibits
polymerization of cell wall
components in susceptible
bacteria.
AMINOGLYCOSIDES  Streptomycin, Amikacin, Inhibition of protein biosynthesis

Gentamicin, Sisomicin, by irreversible binding of the
Kanamycin, Netilmicin aminoglycoside to the bacterial
Tobramycin, Paromomycin, ribosome 30S subunit.
Neomycin, Framycetin
 Tetracycline ,Doxycycline Inhibits bacterial protein

TETRACYCLINES Oxytetracycline, Minocycline, synthesis by binding with the
Demeclocycline 30S ribosomal subunit.
GLYCYLCYCLINES  Tigecycline. Binds to the 30S ribosomal

subunit of rRNA and inhibits the
binding of amino acyl-tRNA.
CHLORAMPHENICOL - Termination of polypeptide

synthesis by binding to the
bacterial 50S ribosomal subunit.
LINCOMYCINS  Clindamycin. Binds to the 50S ribosomal

subunit of rRNA and inhibits the
initiation of peptide chain
synthesis.
MACROLIDES  Erythromycin, Roxithromycin, Macrolides are inhibitors of

Clarithromycin, Azithromycin protein synthesis. They impair
the elongation cycle of the
peptidyl chain by specifically
binding to the 50 S subunit of the
ribosome
OXAZOLIDINONE  Linezolid Inhibition of bacterial

ribosomal protein synthesis by
binding to the 23S portion of
the 50S ribosomal subunit.

FLUOROQUINOLONES 1. First generation drugs : Inhibition of topoisomerase

 Norfloxacin , Ofloxacin, (DNA gyrase) enzymes, which
Ciprofloxacin, Pefloxacin. inhibits relaxation of supercoiled
2. Second generation drugs : DNA and promotes breakage of
 Levofloxacin, Moxifloxacin double stranded DNA.
Lomefloxacin, Gemifloxacin
Sparfloxacin, Prulifloxacin.
NITRO IMIDAZOLES  Metronidazole, Tinidazole, It diffuses into the organism,

Ornidazole. inhibits protein synthesis by
interacting with DNA and causing
a loss of helical DNA structure
and strand breakage. Therefore, it
causes cell death in susceptible
organisms.
RIFAMYCINS  Rifamycin, rifampin, rifabutin, Rifamycins bind to and inhibit

rifapentine, rifalazil and DNA-dependant RNA
rifaximin. polymerase.
SULFONAMIDES 1.Short acting (4-8 hr) : They are competitive inhibitor of

 Sulfadiazine bacterial enzyme dihydropteroate
2. Intermediate acting (8–12 hr): synthetase. This enzyme normally
 Sulfamethoxazole uses para-aminobenzoic acid
3. Long acting (~7 days): (PABA) for synthesizing the
 Sulfadoxine, necessary folic acid. The inhibited
Sulfamethopyrazine reaction is normally necessary in
4. Special purpose sulfonamides: these organisms for the synthesis
 Sulfacetamide sod., of folic acid. Without it, bacteria
Mafenide, cannot replicate.
Silver sulfadiazine,
Sulfasalazine
It binds to dihydrofolate
TRIMETHOPRIM reductase and inhibits the
reduction of dihydrofolic acid
- (DHF) to tetrahydrofolic acid
(THF). THF is an essential
precursor in the thymidine
synthesis pathway and
interference with this pathway
inhibits bacterial DNA synthesis.

NITROFURAN  Nitrofurantoin It is activated inside bacteria

by reduction via the
DERIVATIVE
flavoprotein nitrofurantoin
reductase to unstable
metabolites, which disrupt
ribosomal RNA, DNA and
other intracellular components.
It is bactericidal, especially to
bacteria present in acid urine.
POLYPEPTIDES  Polymyxin B, Colistin, Polymyxin and Colistin

Bacitracin disrupts bacterial cell
membrane phospholipids.
They may also inactivate the
bacterial endotoxin.
Bacitracin inhibits bacterial

cell wall synthesis. This is
achieved by preventing the
final dephosphorylation step in
the phospholipid carrier cycle,
which interferes with the
mucopeptide transfer to the
growing cell wall.
1.4 CDC CLASSIFICATION OF ANTIBIOTIC-RESISTANT BACTERIAL

INFECTIONS: Assessment of Antibacterial Resistance Threats 9
The CDC assessed antibiotic-resistant bacterial infections according to seven factors: clinical
impact, economic impact, incidence, 10-year projection of incidence, transmissibility,
availability of effective antibiotics, and barriers to prevention. The threat level of each bacteria
was then classified as “urgent,” “serious,” or “concerning” (Table no. 2). In general, threats that
are urgent or serious require more monitoring and prevention activities, whereas those
considered concerning require less.

Table 2. CDC Assessment Of Antibacterial Resistance Threats
URGENT THREATS SERIOUS THREATS CONCERNING THREATS
 Carbapenem -resistant  Drug-resistant  Erythromycin-resistant group

Acinetobacter Campylobacter A Streptococcus
 ESBL-producing
 Clostridioides difficile Enterobacteriaceae  Clindamycin-resistant group
B Streptococcus
 Vancomycin-resistant
 Carbapenem-resistant Enterococci
Enterobacteriaceae  Multidrug-resistant
Pseudomonas aeruginosa
 Drug- resistant Niesseria  Drug-resistant nontyphoidal
gonorrhoeae Salmonella
 Drug-resistant Salmonella
serotype Typhi
 Drug-resistant Shigella
 Methicillin-resistant
Staphylococcus aureus
 Drug-resistant Streptococcus
pneumoniae
 Drug-resistant Tuberculosis
1.5 EMERGENCE OF AMR:
The discovery of antibiotics has saved several lives but it has also emerged many resistant strains
of pathogens. After the discovery of the first antibiotic penicillin in the year 1928, the whole
course of medicine was completely changed and it has enabled all the health care professionals
to treat various life-threatening conditions and illnesses. Soon after penicillin, scientists have also
introduced beta lactam antibiotics to maintain the usage of antibiotic strategies. For the first time,
in late 1950s and early1960s, resistance against many antibiotics was observed among E.coli,
Salmonella and Shigella which belong to the class of enteric bacteria. The detection of these
resistant strains has led to great clinical and economic losses along with loss of life. This
emergence of resistance was considered as a mild problem in the developed world as it was
restricted to only enteric bacteria. But later in 1970s, this misconception was changed when

resistance of Neisseria gonorrhoeae and Haemophilus influenzae was found against ampicillin,
while resistance of Haemophilus was reported against tetracycline and chloramphenicol as well.
Later, in 1972 vancomycin was discovered but unfortunately methicillin resistant
Staphylococcus aureus (MRSA) strains were detected in countries like US and UK in the same
years when new antibiotics were discovered. Since few decades, resistance against quinolones,
carbapenems, and third generation cephalosporins has been rapidly increasing in the community.
Till 1980s many antibiotics were developed and introduced to solve the resistance issue, but as
the years passed on, the pace in discovering new antibiotics staggered. The discovery of
antibiotics has saved several lives but it has also emerged many resistant strains of pathogens.
After almost 70 years since when the first patient was treated with antibiotics, the occurrence of
bacterial infections has become one of the life-threatening conditions in today’s world. When
focused on other side of antibiotics other than emergence of resistance, these drugs have many
break throughs that have handed to the mankind. Antimicrobial agents have not only treated and
prevented bacterial infections, but also treated infections that occur during various surgeries like
joint replacement, organ transplantation, hepatic surgeries, cardiac surgeries, chemotherapy and
many more. Other than these, it also increased the average life expectancy and decreased the
morbidity and mortality rate.10
1.6 MECHANISMS OF RESISTANCE:
The genetic basis of resistance has to translate into bacteria survival by counteracting the effect
of the antibiotic. This can be accommodated in several ways or by combinations of these in
which changes to the genetic material or acquisition of new genetic material, results in either: i)
modification to the antibiotic target, ii) Limiting access to the antibiotic target and/or iii)
modification of the antibiotic. Resistance to many antibiotics is often accommodated through a
combination of these mechanisms.
1) Modification of the target
Resistance to several important antibiotics is accommodated through changes to the target of the
antibiotic, thereby changing the affinity of the antibiotic to the target. Rifampicin resistance is
acquired by mutations to the RNA polymerase beta-subunit (rpoB) gene in E. coli11
Mycobacterium tuberculosis.12,13 Fluoroquinolone (ex. Ciprofloxacin) resistance is mediated

through sequential acquisition of mutations in the gyrA, gyrB genes (DNA gyrase, primarily
target of fluoroquinolones in Gram-negative bacteria) and parC, parE genes (topoisomerase IV
genes, primarily target of fluoroquinolones in Gram-positive bacteria) depending on the
individual fluoroquinolone and bacterial strain.14 This mode of protection can also be
accommodated through carriage of alternative copies of the target protein, inducible when
neededand enabling the bacterium to survive. In methicillin-resistant Staphylococcus aureus
(MRSA) themobile genetic element SCCmec (staphylococcal cassette chromosome mec)
harboring the mecA gene that encodes an alternative penicillin binding protein (PBP2a) induced
by β-lactams and with low affinity for β-lactam antibiotics.15,16
Figure 2: Mechanisms of resistance. Modification of the target; changes the affinity of the
antibiotic for the target, this can also be mediated through production of multiple variants of the
target (not shown). Limiting access to the target; mediated through efflux of the antibiotic or
lowered permeability of the cell. Modification of the antibiotic; by enzymatic activity the
antibiotic can be degraded or modified to an inactive form.
2) Limiting access to the target
Many antibiotics exert their effect by interaction with intracellular target. Limiting access to the
intracellular environment of the cell is an important determinant of antibiotic resistance. In
bacteria, efflux mechanisms are highly diverse and important resistance determinants reviewed

in detail elsewhere.17 Usually efflux is accommodated through molecule specific or multidrug

non-specific extrusion of antibiotics via passive or active transport across the membrane.17
Resistance through efflux is highly problematic in antimicrobial and cancer treatment, but in
bacteria transporters are mainly of the passive type, in contrast to resistance to anticancer
compounds in mammalian cells.18 In bacteria transporters are highly diverse in nature and
divided into five major families; I) The major facilitator family (MF), II) The ATP-binding
cassette (ABC) family, III) the resistance-nodulating division (RND), IV) the drug/metabolite
transporter (DMT) family and V) the multidrug and toxic compound extrusion (MATE) family.17
Non-specific multidrug-resistance determinants are usually chromosome encoded and most
likely not evolutionary intended for drug transport. Whereas efflux of antibiotics by drug specific
transporters and often found on plasmids.17 The plasmid carried tet genes of E. coli encode the
membrane associated Tet proteins (MF family), that are antiporter that extrude tetracycline in
exchange of a H+.19,20 Likewise chloramphenicol resistance can be accommodated by carriage of
the gene (cmlA)encoding a protein transporter (MF family) that accommodates efflux of
chloramphenicol.21 In Salmonella enterica multidrug resistance to quinolones, chloramphenicol
and tetracycline`s has been shown to be mediated through over expression of AcrAB-TolC
(RND transporter).22
Importantly, resistance by limiting access of the antibiotic can also be mediated by changing the
permeability of the membrane. In the Gram-negative bacterium Pseudomonas aeruginosa
imipenem resistance is mediated via several mechanisms among which loss of the outer
membrane porin, OprD, is a major facilitator.23 Likewise, elevated tolerance to vancomycin in
the Gram-positive bacterium S. aureus can be mediated through thickening of the cell, as first
observed by Hiramatsu et al.24
3) Modification of the antibiotic
Resistance to antibiotic compounds by degradation or modification of the active compound is of

huge clinical importance. Chloramphenicol resistance can be mediated by carriage of a
constitutive active (E. coli) or inducible (S. aureus) chloramphenicol acetyltransferase cat
gene.25,26 This encodes the CAT enzyme that is capable of transferring an acetyl group from
Acetyl-Coenzyme A to chloramphenicol, blocking binding of chloramphenicol to the ribosomal
subunit.

Likewise aminoglycoside resistance is mediated by aminoglycoside modifying enzymes such as

acetyltransferase (AAC), adenylyl transferases (ANT) or phosphotransferases (APH) that modify
aminoglycosides.27 Finally Sir Alexander Flemming himself discovered the production of β-
lactamase enzymes capable of hydrolyzing β-lactam antibiotics such as penicillin.28
1.7 GLOBAL SITUATION OF AMR:
The surveillance on AMR made by WHO in 2018, revealed high levels of resistance against
numerous bacterial infections in both high and low-income countries.29 In few surveillances e.g.
The Alexander Project, which limited the antimicrobial resistance to only community acquired
pneumonia revealed that highest resistance rates were demonstrated in countries which have the
highest per capita consumption of antimicrobial agents.30 The new Global Antimicrobial
Surveillance System (GLASS) of WHO, has shown a wide spread occurrence of AMR among
5,00,000 people with suspected infections caused by various bacteria across 22 countries.
Penicillin is one of the commonly used antibiotics worldwide in the treatment of pneumonia
since decades, WHO has stated the resistance against this first discovered antibiotic ranged from
0- 52% among the reporting countries. In case of E.coli associated with urinary tract infections,
its resistance against ciprofloxacin was found to be 8 - 65%. Dr Marc Sprenger who is the
director of WHO’s Antimicrobial Resistance Secretariat, said that the reports have confirmed a
serious situation of AMR worldwide. He mentioned that the most common and potentially
dangerous infections are proving resistance against the many antimicrobial agents. He also added
that, the most worrying thing is the pathogens don’t respect the national borders hence, the WHO
is encouraging all the countries to set a standard surveillance system for detecting the AMR so
that all the countries can provide data to this global system. Till date, 52 countries have enrolled
in WHO’s GLASS. “The very first report included 40 countries which provided information on
National surveillance system and 22 countries have reported the levels of resistance against
antibiotics” says Dr Carmem Pessoa- Silva who co-ordinates WHO’s new surveillance system.
In the first report of GLASS, the presented data by different countries varied in quality and
completeness. It was found that in some countries, building their own national surveillance
system was a major problem due to lack of personnel, funds and also infrastructure. However, to
produce a reliable and meaningful data, WHO is supporting many countries to set up national
antimicrobial resistance surveillance system. 29

Drug resistant surveillance programs in HIV, TB are functioning since many years and these
programs have helped in estimation of disease burden, monitoring the effectiveness of control
interventions and in framing a plan for diagnostic and treatment services. Besides these, the
programs have also helped in designing an effective treatment regimen to prevent future
resistance. The rollout of GLASS has already made a huge difference in many countries,
example: In Kenya, the development of its national AMR system has been enhanced. To align
with the GLASS methodology, the republic of Korea has revised its complete surveillance
system to provide complete data and maintain high quality of data. Countries like Cambodia and
Afghanistan faced many structural challenges and have enrolled in this system to strengthen their
AMR surveillance capacities by following WHO’s GLASS framework. So, in general, the
national enrolment in GLASS has indicated a political commitment to support the global efforts
in controlling antimicrobial resistance. The rate of AMR in particular species of microbes varies
significantly from one country to another. 29
The MYSTIC (Meropenem Yearly Susceptibility Test Information Collection), which is a

multicentred, global surveillance involves the comparison of meropenem activity with that of
imipenem, piperacillin + tazobactum, ceftazidime, gentamycin and ciprofloxacin. Out of 46
centres (ICUs, general wards, neutropenia units, cystic fibrosis units) which contributed in this
study, 26 centres were in Europe, 14 in America and 3 in the Middle East and Asia. The results
in the first year of this study for the common isolates were obtained from these countries. The
study results have shown that meropenem has a broad- spectrum activity, the potency was 89%
of 6890 strains and the MIC was tested to be > or = 4mg/ml. The study had also revealed that the
overall susceptibility was less to the comparator antimicrobials. 31 Many national and
international studies which limit their study to an individual organism like WHO programme into
tuberculosis, can demonstrate resistance outbreaks and disseminate resistant strain but these
studies, fail in monitoring the spread of resistance between species and also the broader
emergence of AMR. In most recent studies like MYSTIC surveillance programme, have tried
linking the AMR with the date of prescribed antimicrobials to monitor the geographical spread
and selection pressure which resulted from usage of antimicrobial agents.30
In the recent surveillance on antimicrobial resistance conducted by ECDC, it was reported that
the prevalence of methicillin-resistant Staphylococcus aureus is stabilizing and also decreasing in

some of the countries. The study has also showed a sharp and wide spread increase of resistance
and multidrug resistance against cephalosporins, specifically third generation cephalosporins in
E.coli, Klebsiella species.32
Figure 3: Antibiotic Resistance Worldwide Info graphic.

Source: https://www.biomerieuxconnection.com/wp-content/uploads/2017/12/antibiotic-
resistance-worldwide-infographic.pdf
AMR is now a global concern as it is spreading throughout the world and is one of the serious
public health problem of 21 st century which increases interferes with the effective outcomes. 33
The main impact of AMR is that it results in inability to treat common infections due to the
emergence of new mechanisms of resistance, extended hospital stays with increased health care
cost, prolonged illness, disability and death. As the resistance against several antibiotic increase,
the requirement of intensive care also increases. 33,34 The main causes of AMR are self-
medication, over use or misuse of antibiotics, non-judicious use of antibiotic fixed dose

combinations, inappropriate antibiotic prescribing, international migration of public, use of

antibiotics in agriculture and in poultry as growth promoters, poor sanitation as it may increase
the spread of antibiotic resistant bacteria and poor infection control practices in health care
setting.31 Resistance against antibiotics is present in almost all the countries in the world. There
is an increased risk of severe clinical outcomes and death in people who are infected with drug-
resistant strains of bacteria and also consume more health care costs than that of people who are
infected with non-resistant strains.34 In most of the developing countries, one of the main causes
of AMR is the easy availability of antimicrobial agents which can be purchased as a commodity
even without any prescription issued by a health care provider or physician. 35 Non-compliance is
the term used when an individual forgets taking the prescribed medication or prematurely stop
taking the medication with an intention that the condition has been resolved. So, being non-
adherent or non-compliant with the recommended treatment which include antibiotics in the
regimen is one of the most common human behaviour which can result in AMR.36,37 Besides all
these factors, failure in developing or discovering new antibiotics in the 1930s-1960s which was
considered as the golden era of antibiotics is considered as a predisposing factor associated with
the emergence of AMR.32 APUA (The Alliance of Prudent Use of Antibiotics) is an organization
found in 1981. It has collaborated with 35 countries on research and education on antibiotic use
and resistance. This organization has championed in improved use of antibiotics globally for 20
years.33 According to the CDC’s 2019 threat reports of antibiotic resistance in U.S, each year
more than 2.8 million of antimicrobial resistant infections occur and as result more than 35,000
individuals die of it. The report consists of 18 antibiotic resistant strains of microbes and based
on the level of concern to the human health, the list is divided into three categories namely-
serious threats, urgent threats and concerning threats. 9 Many preventive measures and infection
control efforts are being made in U.S to reduce the infections and deaths which resulted from
antibiotic-resistant strains of bacteria. More action is need to completely protect individuals
because the number of individuals facing the problem of AMR is still too high. 38
1.8 INDIAN SCENARIO OF AMR:
India is now considered as a capital country of AMR in the world and is facing new diagnostic
and therapeutic challenges because of newer multidrug resistant (MDR) organisms, on the other
hand, the country is still in the mission to combat TB, cholera pathogens which are becoming

more resistant on passage of time. 39 There is a huge burden of antibiotic resistance and MDR in
India. Salmonella typhi, Shigella, Pseudomonas and Acinetobacter are the highly reported drug-
resistant pathogens as per the regional reports of AMR studies. More than 50,000 new-borns per
year effected with sepsis die due to the pathogens resistant against first line antibiotics. By the
year 2050 in India, two million people are expected to die due to AMR. The emergence of
enzyme New Delhi metallo-β-lactamase (NDM-1) which is named after the capital of India has
spread to many other countries rapidly in the year 2008. 40 The bacteria can be differentiated from
each other based on the mechanisms by which they develop resistance. Novel mechanisms and
dissemination of antimicrobial resistance have been observed [example: New Delhi metallo-β-
lactamase (NDM-1)] over the last few decades. Carbapenems like meropenem, imipenem and
colistin are the drugs which are considered and last resort antibiotics and drug resistant
mechanisms of these antibiotics in gram- negative bacteria and resistance against colistin are
reported in India.41 About 29% of staphylococcus isolates were found resistant against penicillin
in 2008 and it has risen to 47% in the year 2014. The proportion of methicillin-resistant
Staphylococcus aureus (MRSA) was found to be decreasing in the countries with effective
antibiotic stewardship and/or infection prevention and control programs. 40 Another alarming
problem is the rise of “superbugs” i.e multidrug resistant organisms which can be treated with
only high end antibiotics.41 The interdependence of animals, humans and environmental
parameters also contribute antibiotic resistance. There is a disproportionate raise of AMR in
these three sectors since decades.39
AMR in man:
According to the “Scoping report of AMR in India 2017”, the antibiotics fluoroquinolones and
third generation cephalosporins were found to be ineffective in more than 70% isolates of E. coli,
Klebsiella pneumoniae, Acinetobacter baumanii and half of the Pseudomonas aeruginosa due to
the resistance. In case of drug combinations, piperacillin + tazobactum was <35% resistant to E.
coli and Pseudomonas aeruginosa and 65% of K. pneumoniae were resistant to carbapenems due
to the presence of multi resistant genes. Colistin is used frequently as a last resort antibiotic due
to the increasing rate of resistance against carbapenems which was found to be 71% in A.
baumanii. In India, resistance to colistin has emerged and due to the colistin- resistant
K.pneumoniae, a high mortality of 70% has been reported. Among gram- positive organisms,

methicillin resistance is seen in 46% of Staphylococcus aureus and vancomycin resistance in

10.5% of Enterococcus faecium.
AMR in food animals:
In order to increase the productivity of milk, fish and many other marine food, abundance of
antimicrobials are used in food animals. When the milk samples for AMR estimation were
analysed, 48% of gram-negative bacilli found in cow and buffalo milk were ESBL producers
(West Bengal) and 47.5% were resistant to oxytetracycline (Gujarat). Among the gram-positive
bacteria found in analysis of these milk samples, there was 2.4% of vancomycin resistance,
24.4% of methicillin resistance was seen in S. aureus and 5.6% of coagulase negative
Staphylococcus was reported. 48% of Enterobacteriaceae were isolated in the gut of tilapia fish
found in the lakes of Maharashtra were ESBL producers.
AMR in environment:
Ganga and Yamuna, which are the two largest rivers in India, occupy massive area of land and
receive multiple inlets which contain drug resistant bacteria. 17.4% were ESBL producers among
gram negative bacteria in these north Indian rivers. In south Indian rivers, Cauvery (Karnataka)
was isolated with 283 isolates of E. coli, which was 100% resistant against third generation
cephalosporins. Apart from these rivers, the samples of the surface water and ground water used
for drinking and recreational purposes were collected from lakes, ponds, tube wells, springs,
hand pumps etc for the estimation of AMR. These samples revealed that the isolates of E. coli
were 17% resistant to third generation cephalosporins in central India, 100% in south India, 7%
in north India and 50% in east India (Sikkim). 39
1.9 FACTORS CAUSING ANTIBIOTIC RESISTANCE:

1. ANTIBIOTIC CONSUMPTION IN HUMANS:
Antibiotic use is a major driver of resistance.42 Based on antibiotic sales data, in 2014, India was
recorded as the highest consumer of antibiotics, followed by China and the United States.
However, the per capita utilization of antibiotics in India is much lower than in several other
high income countries. Possible reasons for high AMR rates in India are discussed in this
section.43

a. Over use of antibiotics :

The overuse of antibiotics leads to develop resistance.44 A direct relationship between antibiotic
utilization and the emergence and dissemination of resistant bacteria strains was demonstrated in
a epidemiological studies.45 In bacteria, genes can be innate from relatives or can be acquired
from non relatives on itinerant genetic elements such as plasmids. This horizontal gene transfer
(HGT) allows antibiotic resistance to be transferred among different species of bacteria.
Spontaneously, through mutation resistance can also occur. Antibiotics take away drug-sensitive
competitors, parting resistant bacteria behind to reproduce as a result of natural selection.46
Regardless of warnings regarding over use, antibiotics are overprescribed across the world.45
b. High consumption of broad-spectrum antibiotics:
Broad-spectrum antibiotics are those which are effective against a wide range of disease causing
bacteria, in difference to narrow-spectrum antibiotics, which are effective against specific
families of bacteria. Broad-spectrum antibiotics are most commonly prescribed empirically when
there is a wide range of possible illnesses which may lead to potentially serious illness if
treatment was delayed. However, unwanted use of broad-spectrum antibiotics leads to increased
incidence of MDR bacteria.47 Between 2000 to 2015, cephalosporin and broad spectrum
penicillin utilization increased hastily, whereas the usage of narrow spectrum penicillin
consumption was low and decreasing (Figure 4).
Figure 4: Trends in antibiotic consumption in India, 2000–2015

Source: http://www.pnas.org/cgi/doi/10.1073/pnas.1717295115

Utilization of broad-spectrum antibiotics, mainly third-generation cephalosporins, has increased

significantly. The high use of third generation cephalosporins is due to multiple factors. First,
fluoroquinolones have been the main basis of treatment for enteric fever and bacterial dysentery,
but due to increasing quinolone resistance, third-generation cephalosporins are used as empiric
treatment choices for these two common infections.48 The second reason is altering prescribing
practices among the healthcare providers. Third generation cephalosporins are being substituted
with penicillins in the treatment of upper respiratory tract infections in outpatient department and
lower respiratory tract infections in inpatient settings.49 The third reason is mostly due to lack of
widespread accessibility of narrow-spectrum agents such as first penicillins (penicillin G,
benzathine penicillin) which are first generation in compare to third-generation cephalosporins in
the pharmacies.50
c. Increasing faropenem consumption:
With the escalating prevalence of community-acquired and health care associated third
generation cephalosporin-resistant bacterial infections, penem and carbapenem consumption is
increased mostly in India.51 However, the utilization of faropenem, which is an oral penem, a
broad-spectrum antibiotic, increased 150% between 2010 and 2014. In India, faropenem is
accepted for treatment of a variety of common infections like respiratory tract, urinary tract, skin
and soft tissue, and gynecological infections. The quick increase in use of faropenem is of
distress because of the potential for cross-resistance to carbapenems. At present, susceptibility
testing against faropenem is not usually performed in microbiology laboratories due to a lack of
guidelines from the Clinical & Laboratory Standards Institute (CLSI) or the European
Committee on Antimicrobial Susceptibility Testing (EUCAST). There is at present a lack of
understanding regarding the resistance situation and selection potential of faropenem with
carbapenems.
d. Antibiotic fixed dose combinations:
Antibiotic fixed-dose combinations (FDCs) are the combinations of two or more active
antibiotics in a single dosage form. Antibiotic FDCs should be given when the combination has a
proven advantage over the single compounds administered individually in therapeutic effect,
safety, or compliance. However, in India, antibiotic FDCs are greatly prescribed even without

the data of a proven advantage over single compounds. Lack of diagnostic accuracy due to
unavailability of diagnostic laboratory services has led to increased use of antibiotic FDC across
India.52 Inadvisable use of antibiotic FDCs could lead to emergence of bacterial strains resistant
to multiple antibiotics. Approximately 118 antibiotic FDCs are currently available in India.
These FDCs include both oral broad-spectrum antibiotics such as third-generation
cephalosporin’s and last chance antibiotics such as linezolid. The following are some of the
common FDCs available in India.53
 Azithromycin-Cefixime
 Cefixime-Ofloxacin
 Cefixime-Levofloxacin
 Cefixime-Linezolid
 Azithromycin-Levofloxacin
2. SOCIAL FACTORS:
Numerous social factors have been associated with inappropriate antibiotic use in India among
the general public and formal healthcare providers.
a. Self-medication is used primarily to avoid the financial load of expensive allopathic medical
visits and is compounded by the accessibility of drugs without a prescription. The major sources
of self-medication are earlier doctors’ prescriptions and available medicines from previous
illnesses.54 Self-medication with antibiotics is a common carry out for infections such as the
common cold, demonstrating a lack of knowledge of when to use antibiotics. 55 In rural areas,
when there is a short of healthcare services in their village, people may want to evade the travel
cost to get allopathic services and instead approach informal health care providers and chemists
or pharmacists at pharmacy stores. In urban areas, doctor charge fees and diagnostic
investigation charges may stop people from visiting proper healthcare providers. 56
b. Factors related with rational antibiotic prescribing include: Doctors in private sector may
distinguish that they are duty-bound to give antibiotics as patients come with defined ideas and
demand fast relief. The diagnostic uncertainty due to the incapability to perform investigations
leads physicians to prescribe broad spectrum antibiotics because of the fear of clinical failure.

Pharmaceutical companies put stress on doctors and pharmacists to prescribe new antibiotics,
and in return they collect incentives. 56
Physicians in the public division have to see a vast number of patients in a limited time period.
Thus these physicians do not have adequate time to counsel patients against the use of antibiotics
and instead advise them. Primary care services and secondary care hospitals in the public sector
do not have microbiology, diagnostic laboratory services. 57
Patients visiting public sector physicians cannot afford investigations in private labs, thus
compelling physicians to prescribe antibiotics. The medicines contribute in the public sector
could be unpredictable, with no supply during some months and oversupply during other months,
and could have drugs close to their expiration. To dispose of the medicines before they expire,
doctors in the public sector may recommend antibiotics even though they are not required for the
patient. Some factors are common to both public and private sector healthcare. Providers such as
varying knowledge on the problem of AMR and lack of continuing medical education on this
problem.57
3. ANTIBIOTIC CONSUMPTION IN FOOD ANIMALS:
Utilization of antibiotics as growth promoters in food animals in poultry is a common practice.

The agricultural usage of antibiotics also affects the environmental microbiome. Up to 90% of
the antibiotics given to domestic animals are excreted in urine and stool, then widely dispersed
through fertilizer, groundwater, and surface runoff.44
The most common antimicrobials identified were enrofloxacin (20%), ciprofloxacin (14.3%),
doxycycline (14.3%), oxytetracycline (11.4%), and chlortetracycline (1.4%).58 A more relating to
issue is the usage of polymyxins (colistin) for growth promotion, prophylaxis, and therapeutic
purposes in poultry, as this category of drugs is the last chance medicine. Because of the
emergence of plasmid mediated resistance with use of polymyxins in food animals and potential
transfer of this gene to humans, there is an immediate need to ban the use of antibiotics that are
used for growth promotion in food animals. 59

4. ENVIRONMENTAL SANITATION:
Antibiotic selection pressure is a prerequisite for the appearance of resistance; however, poor
sanitation plays a important role in the spread of antibiotic-resistant bacteria. A large fraction of
sewage is disposed untreated into receiving water bodies, leading to gross contamination of
rivers with antibiotic residues, antibiotic-resistant organisms.60
5. INFECTION CONTROL PRACTICES IN HEALTH CARE SETTING:
The occurrence of various health care associated infections (HAIs) among Indian hospitals
ranges from 11% to 83%, in contrast to the WHO estimate of about 7% to 12% of the HAI
burden among hospitalized patients globally. 61
Figure 5: Spread of Antibiotic Resistance.

Source: https://www.biomerieuxconnection.com/wp-content/uploads/2017/12/how-antibiotic-resistance-
spreads-infographic.pdf

1.10 TREATMENT GUIDELINES FOR INFECTIONS: 62

a. Urinary Tract Infections:
Table 3. Empiric Treatment Regimens For Urinary Tract Infections, (When Culture
Results Are Awaited)
Drug Of
Urinary Syndrome Alternative Choice Comments
Choice
Acute cystitis •Nitrofurantoin •Co-trimoxazole • Dosage adjustment as per

• Fosfomycin • Ertapenem eGFR.
• Amikacin (can be used • Fosfomycin and
in children as well) nitrofurantoin should be
avoided when there is
suspicion of pyelonephritis or
prostatitis / presence of
systemic features of infection.
• Fosfomycin susceptibility to
being requested for, and used
only for Gram-negative MDR
organisms.
Acute Prostatitis •Ertapenem 1 g •Piperacillin/tazobactam •Urine and prostatic massage

IV once daily • Imipenem specimen for cultures to be
• Meropenem collected before antibiotics.
• Co-trimoxazole •Prostatitis requires a
minimum of 21 days
antibiotics.
Epididymoorchitis Ceftriaxone + • Ofloxacin Total duration of treatment is

(High risk of Doxycycline •Levofloxacin 14 days (except for
sexually transmitted) Levofloxacin where it is 10
days)
Epididymoorchitis Ceftriaxone + • Ofloxacin Total duration of treatment is

(High risk of Doxycycline •Levofloxacin 14 days (except for
sexually transmitted) Levofloxacin where it is 10
days)
Epididymoorchitis • Ofloxacin
(Low risk of sexually • Levofloxacin
transmitted; likely
due to enteric or
urinary organisms)

Table 4. Standard Doses Of Antimicrobial Agents Used In Urinary Tract Infections
Antibiotics Doses, Duration And Route Of Administration
Acute Cystitis
1. Nitrofurantoin 100mg BD for 5 days
1. Nitrofurantoin 1.25-1.75 mg/kg oral 6 hourly (Dose in children)
2. Fosfomycin 3.0 g single dose
3. Co-trimoxazole ds 1 tab BD for 3 days
4. Ertapenem 1 g IV once daily for 7 days
5. Amikacin 15mg/ kg/day once daily IV or IM for 3 days Acute
Pyelo-nephritis
Acute Pyelo-Nephritis
6. Piperacillin/tazobactam 4.5g IV, 6 hrs
7. Ertapenem 1 g IV, once daily for 7 -10 days
8. Imipenem 1 g IV, q8h
9. Meropenem 1 g IV, q8h
10. Amikacin 15mg/kg/day, once daily IV/IM for 7-14 days
Acute Prostatitis
11. Ertapenem 1 g IV, once daily for 7 -10 days
12. Piperacillin/tazobactam 4.5 g IV, 6 hrs
13. Imipenem 1 g, 8 hourly
14. Meropenem 1g IV, q8h
15. Co-trimoxazole (160-800mg) BD
Epididymo-Orchitis
16. Ceftriaxone 500 mg, IM
17. Doxycycline 100 mg, BD
18. Ofloxacin 200 mg, BD
19. Levofloxacin 500 mg, OD

b. SEPSIS:
Table 5. Antimicrobial Choice For Sepsis Condition
Diagnosis Suggested Regimens Remarks
Preferred Alternative
Sepsis or septic shock Imipenem- Meropenem or •Septic shock patient must receive
with focus unclear Cilastatin +/- Cefoperazone empiric combination therapy with
Amikacin Sulbactam at least two antibiotics of different
+/- Amikacin
antimicrobial classes.
•Add MRSA or CR-GNB
Rule out common +/- +/- coverage or antifungals in
tropical infections Vancomycin Vancomycin patients with appropriate risk
Teicoplanin or Teicoplanin factors
+/- Doxycycline •Avoid Piperacillin-tazobactam in
+/- Colistin or septic shock till bacteraemia with
Polymyxin B
cephalosporin resistant organisms
is excluded, as mortality increases
Refer to appropriate *If risk factors (MERINO trial)6
sections for empirical for Candida add •De-escalation of antimicrobials
antibiotic therapy for an Echinocandin should be considered daily and at
different sites of (Caspofungin or the earliest stage when the clinical
infection Micafungin or situation permits/ once culture
Anidulafungin)
susceptibility reports are
available**
•Treatment duration of 7 to 10
days is adequate for most cases.
•Longer courses appropriate in
slow clinical response,
undrainable foci of infection,
bacteraemia with S.aureus, some
fungal and viral infections, or
immunologic deficiencies.
•Measurement of procalcitonin
levels can be used to support
shortening the duration of
antimicrobial therapy.

Table 6. Standard Doses For Antimicrobial Agents Used In Sepsis
Antibiotics Doses, Duration and Route of Administration

Imipenem-Cilastatin 500 mg IV q6h or 1 g q8h.
Amikacin 15 mg/kg IV q24h.
Meropenem 1gm IV q8h.
Cefoperazone – Sulbactam 3g IV q12h.
Vancomycin 15 mg/kg IV q8–12h.
Teicoplanin 400mg IV every 12h for 3 doses followed by
400mg IV q24h.
+/- Doxycycline 100 mg IV q12h.
+/- Colistin 9mu iv stat, then 4.5 mu IV q12h.
Polymyxin B 15-20 lakh units iv stat, then 7.5 -10 lakh IV q12h.
Caspofungin 70 mg IV on day 1, then 50 mg IV q24h.
Micafungin 100 mg IV OD.
Anidulafungin 200 mg iv stat then 100 mg IV OD.
c. RTI AND CAP:
Table 7. Antimicrobial therapy in URTI
Condition Preferred drug Alternative Penicillin allergy
Streptococcal Penicillin V (not Amoxicillin, Anaphylactic: Clindamycin/

pharyngitis easily available in Benzathine Clarithromycin/ Azithromycin
India, Penicillin G penicillin single Non-Anaphylactic: Cephalexin/
not a substitute since dose Cefadroxil.
oral absorption is
poor
Bacterial sinusitis Amoxicillin, Ceftriaxone Adults: Doxycycline/
Co-amoxiclav Cefpodoxime Resp Quinolones
(adults) Children:
Anaphylactic :Resp Quinolones,
Nonanaphylactic: Cefixime And
Clindamycin
Acute otitis media Amoxicillin, Cefpodoxime, Anaphylactic: Azithromycin/
Co-amoxiclav cefuroxime, Clarithromycin
cefdinir, Non Anaphylactic:Cephalosporins.
Ceftriaxone

Table 8. Choice of Empiric Antimicrobial Therapy In Adult CAP
Outpatients Co amoxiclav Macrolides** Beta lactams are preferred over

without co- Cefuroxime macrolides due to high prevalence
morbidities Cefpodoxime of macrolide resistance in S.
pneumoniae in India. Doxycycline
monotherapy not recommended
Outpatients with Co-amoxiclav Cefuroxime/
co-morbidities* or and Macrolide/ Cefpodoxime and
use of Doxycycline Macrolide/
antimicrobial in 3 Doxycycline
months
Inpatient, non-ICU Ceftriaxone Cefotaxime/ If there is hypersensitivity to beta

with Amoxiclav with lactams: respiratory
Macrolide/ Macrolide/ fluoroquinolones (exclude TB first)
Doxycycline Doxycycline
Inpatient ICU Ceftriaxone Cefotaxime,

with macrolide/ Piperacillin/
doxycycline tazobactam with
macrolide
Inpatient ICU with Piperacillin Cefepime/imipenem The use of carbapenems is

risk factors for tazobactam/ with Macrolide/ preferred over beta lactam beta
Pseudomonas Macrolide/ Doxycycline lactamase inhibitor combinations in
aeruginosa/ other Doxycycline patients with septic shock
enteric gram-
negative bacteria#
The empiric addition of Oseltamivir in patients with CAP should be considered in the setting of an
influenza outbreak
If CA MRSA## is suspected then Vancomycin or Teicoplanin may be added.

Table 9. Antimicrobial therapy for pediatric CAP
Outpatient Inpatient
Newborns <1 month Cefotaxime and Gentamicin, add Macrolides if Chlamydia

suspected (afebrile, staccato cough).
Age less than 5 years Amoxicillin, Co-amoxiclav Ceftriaxone, Cefotaxime,

Cefuroxime . Co-amoxiclav.
Age more than 5 years Amoxicillin, Macrolide only Ceftriaxone, Ampicillin,

if clinical features suggestive Co-amoxiclav with/ without
of mycoplasma. Macrolide.
Suspected MRSA: add vancomycin/ teicoplanin / (linezolid only if TB ruled out)
Suspected influenza: Add oseltamivir.
Table 10. Drug Doses, Duration and Route of Administration in RTI and CAP
Drug Adult dose Pediatric dose

•500 mg twice daily •250 mg twice daily
Penicillin V
Benzathine •<27 kg 6,00,000 units IM single dose
penicillin • > 27 kg 1.2 million units IM single dose
Amoxicillin 500 – 1000 mg thrice daily •15-20 mg/kg twice daily oral
(PO or IV) •30-35 mg/kg thrice daily IV
Co-amoxiclav •1 gm twice daily/ 625 mg •15-20 mg/kg of Amoxicillin
thrice daily oral twice daily PO
•1.2 gm IVq8h •25-30 mg/kg of Amoxicillin
component thrice daily IV
Azithromycin •500 mg daily (PO or IV) •10 mg/kg once daily
Clarithromycin •500 mg twice daily •7.5 mg/kg twice daily

Drug Adult dose Pediatric dose

Oseltamivir •75 mg twice daily PO •<15 kg 30 mg twice daily
•16-34 kg 45 mg twice daily
•35 -44 kg 60 mg twice daily
•45 kg and more 75 mg twice daily
Doxycycline •100 mg twice daily •1.5-2 mg/kg twice daily
Clindamycin •300 mg four times a day PO •7 mg/kg thrice daily
•600 mg thrice daily IV
Cephalexin •750 mg twice daily PO •20 mg/kg twice daily PO
Cefadroxil •1 g once daily •30 mg/kg once daily
Levofloxacin •750 mg once daily PO or IV •10-15 mg/kg in one or two
divided doses PO or IV
Moxifloxacin •400 mg once daily PO or IV •10 mg/kg OD, PO or IV
Cefpodoxime •200 mg twice daily •5 mg/kg twice daily
Cefuroxime •500 mg twice daily oral •10 mg/kg twice daily oral
•1.5 g twice daily IV •35 mg/kg twice daily IV
Ceftriaxone •2 g once daily IV •50 mg/kg twice daily
Cefotaxime •2 g thrice daily IV •30-35 mg/kg thrice daily IV
Cefepime •2 g twice daily IV •50 mg/kg twice daily
Piperacillin/tazobactam •4.5 g thrice daily •100 mg/kg Piperacillin TID
Cefoperazone sulbactam •3 g twice daily •50 mg/kg of Cefoperazone twice
daily
Imipenem •1 thrice daily or •15-25 mg/kg four times daily IV
• 500 mg four times daily IV
Meropenem •1 g thrice daily IV •1 g thrice daily IV
Vancomycin •1 g daily •10 mg/kg four times daily
Teicoplanin •400 mg twice daily for 3 •12 mg/kg BD, for 3 doses and
doses and then 400 mg once then 12 mg/kg once daily
daily
Linezolid •600 mg twice daily PO or IV •10 mg/kg TID, PO or IV

1.11 OVERCOMING AND PREVENTION ANTI-MICROBIAL RESISTANCE
Antibiotic resistance occurs as a natural phenomenon as microbes goes on evolving. The pace
at which bacteria develop and disseminate resistance has been accelerated due to human
activities.63 This should be definitely prevented to various threats caused by AMR.
Concerns regarding antimicrobial resistance have been raised frequently over many decades, and
recommendations were suggested to limit its progression. The two major interventions are
infection control to prevent infection transmission and limitation of antibiotic use.
Infection Control
Infection control programs has a significant role in preventing hospital infections. These
programs are very important for effective patient care and risk management in acute care
facilities, regardless of the presence of antimicrobial resistance. Important activities include
surveillance, outbreak investigation and control, patient care practices such as isolation, hand
washing, sterilization and disinfection of equipment. Hospital infection control activity also
decreases colonization and antimicrobial resistant infections. 64
Limiting antimicrobial use
Antimicrobial agents can be life saving for treating patients with bacterial infections but are often
used inappropriately, unnecessarily or without consideration of pharmacokinetic principles when
administered for excessive durations. Large variations in antibiotic consumption exist between
countries, and while excessive use remains as a major problem in some parts of the world,
elsewhere there is lack of access to many antibiotics.63
There are many actions taken for optimizing the antimicrobial use such as restrictive formulary,
treatment based on guidelines for antimicrobial use and antimicrobial resistance reports,
automatic stop orders, education and awareness programmes, dispensing antibiotics only on
prescription etc.64 but the outcome to control the AMR is not effective.

Health organizations of India
AMR surveillance networks were initiated by the Indian Council of Medical Research (ICMR)
and the National Centre for Disease Control in 2013 and 2014, respectively to know the near-
exact extent of AMR. In the year 2015, these two organizations along with cooperation from
Centers for Disease Control and Prevention (CDC), USA has started a systematic assessment of
the prevailing IPC practices in India with the aim of formulating new guidelines for preventing
hospital-acquired infections. These activities, however, deals with the emerging AMR in the
healthcare settings and do not include special provisions for AMR in the environment. The need
to curb AMR in the environment has been realized recently by the national health authorities and
the National Health Policy 2017 calls for ‘a rapid standardization of guidelines regarding
antibiotic use, limiting the use of antibiotics as OTC medications, banning or restricting the use
of antibiotics as growth promoters in animal livestock, and pharmacovigilance including
prescription audits inclusive of antibiotic usage - in the hospital and community’.39
Future directions for India
Antibiotic resistance should be a major concern for India as well as for all countries across the
globe. To advance the effectiveness of antibiotics and to alleviate such problems, the government
of India as well as the international community should establish the following:
1. Guidelines for judicious use of antibiotics not only in the health institutions but also
everywhere associated with the antibiotics and to curb this threat. 65
2. Promoting and supporting the further research on the drivers of AMR with due importance to
components other than antimicrobial use for human health alone.
3. Framing and establishing of antibiotic stewardship plans for all the tiers of healthcare settings
(primary health centres, secondary and tertiary hospitals) to monitor and ensure judicious use of
antimicrobials.39
4. Increase proper immunization coverage that may reduce spread of infections the use of
antibiotics.65
5. Establishing strict vigilance and control over sale of antimicrobial agents.

6. Prescription audit has to performed strictly bring down the over the counter (OTC) sale of
antibiotics.
7. Raising the awareness by educating the masses at the community level regarding AMR and
formulating educational bodies or non-governmental organizations for continued dissipation of
information.
8. Regulating the waste water discharges from pharmaceutical companies and other industries
with regular monitoring of antimicrobial residues in them along with provision of legislative
support to punish offenders.
9. Disciplinary control over the functioning of hospital effluent plants with periodic assessment,
evaluation and reporting of antimicrobial residue in the discharge.
10. Improving agricultural practices by ensuring use of environment friendly manure and
fertilizers.
11. Implementing rules and regulations for the use of antimicrobial agents in food animals. 39
12. Improving Antibiotic prescribing behaviors by physicians and should be aware of their role
and responsibility for maintaining the effectiveness of current and future antibiotic agents
specifically by:
 Adhering to the antibiotic guidelines and clinical pathways.
 Re-assessing treatment based on the culture results and using the shortest duration of
antibiotic agents based on evidence.
 Supporting and enhancing surveillance of antimicrobial resistance and antibiotic use.
 Prescribing and dispensing antimicrobials only when they are truly required based on the
patient situation.
 Most important is to identify and control the source of infection.
 Prescribing and dispensing appropriate antibiotic agents with adequate dosages-i.e.,
administration of antibiotic agents according to pharmacokinetic - pharmacodynamic
(PK-PD) principles.63

CHAPTER - 2
Literature
Review
CHAPTER 2 LITERATURE REVIEW
LITERATURE REVIEW FOR RESISTANCE PATTERNS

1. Moremi N, Claus H et al. (2016) conducted a study entitled “Antimicrobial resistance
pattern: a report of microbiological cultures at a tertiary hospital in Tanzania”. It was a
retrospective study, conducted between June 2013 and May 2015. Out of 3330 culture specimens
which included different samples like blood, urine, cerebrospinal fluid, pus swabs, aspirates,
sputum; 439 (13.2%) showed positive cultures. Staphylococcus aureus (n = 100; 22.8%),
Klebsiella pneumoniae (n = 65; 14.8%) and Escherichia coli (n = 41; 9.3%) were the most
frequently isolated bacteria in this study. Out of 100 Staphylococcus aureus tested, 27 (34.6%)
were found to be methicillin resistant Staphylococcus aureus (MRSA). The rates of resistance of
Klebsiella pneumoniae and Escherichia coli isolates to third generation cephalosporins were
found to be 38.5% (25/65) and 29.3% (12/41) respectively. The resistance rate of gram-negative
bacteria to third generation cephalosporins increased from 26.5% in 2014 to 57.9% in 2015 (p =
0.004) while the rate of MRSA decreased from 41.2% in 2013 to 9.5% in 2015 (p = 0.016). 66
2. Parihar RS., Dallaram et al. (2018) conducted a study entitled “Antimicrobial Susceptibility
Patterns of Blood Borne Pathogens in a Tertiary Care Center, Jodhpur (Rajasthan), India”. It was
a prospective study, conducted between February 2017 to July 2017. The aims of this study
includes isolation and identification of microorganisms from blood samples using automated
BacT/ALERT blood culture system and their antibiotic resistance which 80 samples were
positive for aerobic bacterial isolates. Gram positive isolates (n=54) were found to be
predominant when compared to gram negatives (n=26). Most commonly found organisms in
their study were CONS (Coagulase negative staphylococcus, n=33) and Klebsiella species
(n=07) in gram positive and gram negative isolates respectively. CONS showed maximum
resistance to penicillin followed by erythromycin, clindamycin, levofloxacin and are completely
sensitive to vancomycin where as Klebsiella spp exhibits multi drug resistance with a very high
resistance to beta-lactam antibiotics except imipenem which is sensitive to all strains. 67
3. Nazneen S, Mukta K et al. (2016) conducted a study entitled “Bacteriological trends and
antibiotic susceptibility patterns of clinical isolates at Government Cancer Hospital,
Marathwada”. It was a prospective study, conducted between January 2016 to December 2016.
In this study 170 clinical samples which include urine, blood, sputum, pus were cultured. 110

organisms were isolated from the clinical samples. Gram negative isolates (n=76) were found to
be predominant when compared to gram positives (n=26). Among them most commonly isolated
organisms in their study were E.coli (n=25) and S.aureus (n=17) in gram negative and gram
positive isolates respectively. E.coli showed maximum resistance to 3 rd generation
cephalosporins where as S. aureus exhibits high resistance to fluoroquinolones. 68
4. Paul R, Ray J et al. (2017) conducted a study entitled “Antibiotic resistance pattern of
bacteria isolated from various clinical specimens: an eastern Indian study”. It was a prospective,
observational study , conducted between July 2015 to September 2016. In this study antibiotic
sensitivity was tested by modified Kirby-Bauer disc diffusion method according to The Clinical
and Laboratory Standards Institute guidelines (CLSI) guidelines. A total of 93 clinical specimens
were included such as blood, urine, pus etc. Majorly isolated organisms were found to be gram
negatives (n=57). Among them the most predominating organism was EColi (n=36). Of the gram
positives (n=36) the predominated organism was found to be Staphylococcus (n=32). Ecoli and
Staphylococcus both of them showed high resistance to penicillin and its congeners when
compared to other drugs. In some species resistance to penicillin and cotrimoxazole was upto
100%. Pseudomonas exhibited 75% resistance where as Klebsiella showed 85% resistance to
aminoglycosides.69
5. Bhardwaj N, KhuranaS et al. (2018) conducted a study entitled “Pattern of antimicrobial

resistance of Gram-negative bacilli in surgical site infections in in-patients and out-patients at an
Apex Trauma Center: 2013–2016”. It was a prospective study, conducted between January 2013
to December 2016. This is a 4 years study which involved large study population. Antimicrobial
susceptibility testing was done using disk diffusion method on Mueller‐Hinton agar and by E‐test
for ten antibiotics according to The Clinical and Laboratory Standards Institute (CLSI)
guidelines for Gram‐negative bacilli. In this study antimicrobial resistance patterns were studied
in the admitted patients and in the patients who were followed up to the outpatients department
(OPD) after discharge. There were a total of 2,447 strains which are isolated from the study
population. Out of 2247 strains, 1996 were isolated were isolated from patients who had surgical
site infections (SSI) during the hospital stay, and 451 were from patients who attended the OPD
after discharge. The organisms which were found to be in common in the patients who develop
SSI during their hospital stay were Acinetobacter baumannii (n=622), E.coli (n=424), and

Klebsiella pneumoniae (n=315). Acinetobacter baumannii and E. coli are majorly resistant to
cefepime (n=603; 97%) and ceftazidime (n=380; 90%) respectively. In the outpatients, who
followed up in the OPD for the SSI, Escherichia coli (n=148), and Pseudomonas aeruginosa
(n=93) were found in common, shows high resistance to ceftazidime (n=112; 76%) and
tigecycline (n=77; 83%).70
6. Vadwai V, Nerurkar V et al (2015) conducted a study entitled “Antimicrobial resistance

pattern among community-acquired gram-positive and gram-negative bacteria bloodstream
isolates in India”. It was a retrospective study, conducted between January 2010 to November
2013. This was a 4 years study involving 4811 blood culture positive isolates causing blood
stream infections. Among the culture positive isolates, 1825 were gram-positive and 2986 were
gram-negative isolates. The predominant isolates among gram-positive and gram-negative were
found be Staphylococcus species (n=1585) and E. coli (n=655) respectively. Staphylococcus
aureus (187/372) isolates were resistant to methicillin while showing high susceptibility for
glycopeptides (>95%). Most of the gram negative organisms exhibited high level of resistance to
cephalosporins (>70%), β-lactum agents (>65%) and fluoroquinolones (>50%). It was concluded
that carbapenems and glycopeptides retain high antimicrobial activity against most of the gram
negative and gram positive pathogens.71
LITERATURE REVIEW FOR UTILISATION OF ANTIBIOTICS
7. Orlando V, Monetti VM et al. (2020) conducted a study entitled “Drug utilization pattern of
antibiotics: The role of age, sex and municipalities in determining variation”. It was a
retrospective study, conducted between January 2016 to December 2016. In this study the
analysis of pharmacy records was done to know about drug prescription and antibiotic use by age
and sex. It was found that antibiotic prescription rate was higher in children less than 5 years and
older adults aged more than 70 years. The penicillins were the commonly prescribed antibiotics
accounting to 27% of total number of prescriptions analyzed, followed by cephalosporins
accounting to 14.3% of total prescriptions, 13.1% for macrolides, 12.6% for fluoroquinolones. 72
8. Worku F, Tewahido D (2018) conducted a study entitled “Retrospective assessment of

antibiotics prescribing at public primary healthcare facilities in Addis Ababa, Ethiopia”. It was
a retrospective study, conducted between January 2016 to December 2016. In this study about
900 prescriptions were analysed, and was found that the average number of antibiotics per
prescription was 0.61. The prescription pattern analysis showed that penicillins were most
commonly prescribed accounting to 51.9%, followed by fluoroquinolones (18.3%) and
sulfonamides (11.2%). Among the penicillins, amoxicillin prescribing rate was high which is
51.9%, followed by ciprofloxacin (13.6%), cotrimoxazole (11.2%). 73
9. Dzelamonyuy E Chem, Anong DN et al. (2018) conducted a study entitled “Prescribing

patterns and associated factors of antibiotic prescription in primary health care facilities of
Kumbo East and Kumbo West health districts, North West Cameroon”. It was a retrospective
study, conducted between April 2014 to April 2015. In this study about 30,096 prescriptions
were analyzed and the average number of antibiotics per prescription was found to be 1.14. All
the antibiotics prescribed had broad spectrum activity, among which the most commonly
prescribed was amoxicillin (29.29%), followed by cotrimoxazole (19.08%) and metronidazole
(15.59%). The most common indication for antibiotics was respiratory tract infection (21.27%).74
10. Yimenu DK, Emam A et al. (2019) conducted a study entitled “Assessment of antibiotic
prescribing patterns at outpatient pharmacy using world health organization prescribing
indicators”. It was a retrospective, cross-sectional study conducted between March 5, 2019 to
June 10, 2019. In this study about 600 prescriptions were analyzed, 968 medicines were
prescribed out of which antibiotics account to 58.5%. Among the antibiotic classes penicillins
were most frequently prescribed (38.2%), followed by macrolides (15%). Among individual
antibiotics amoxicillin was most commonly prescribed (28.6%), followed by ciprofloxacin(12%)
and metronidazole (11.1%).75
LITERATURE REVIEW FOR MDR
11. Basak S, Singh P et al. (2015) conducted a study entitled “Multidrug Resistant and
Extensively Drug Resistant Bacteria: A Study”. It was a prospective, cross-sectional study
conducted between April 15, 2014 to July 15, 2014. This is a study which was done to find the
incidence of multidrug resistant (MDR), extensively drug resistant (XDR) and pandrug-resistant
(PDR) bacterial isolates. Antimicrobial susceptibility testing was performed by Kirby Bauer disc
diffusion technique. A total of 1060 bacterial strains were isolated and their antibiotic
susceptibility profile was studied. Among them 393 (37.1%) bacterial strains were MDR, 146
(13.8%) strains were XDR, and no PDR was isolated. Out of 1060 bacterial strains, gram
negative bacilli (n=746;70.4%) were predominantly isolated in which MDR strains were 250
(33.5%), where as gram positive cocci were 314 (29.6%) in which MDR strains were 143
(45.5%). All (100%) Gram positive bacterial strains were sensitive to vancomycin whereas all
(100%) Gram negative bacterial strains were sensitive to colistin. 76
12. Batarseh A, Soneah S et al. (2013) conducted a study entitled “Antibiotic resistance
patterns of multidrug resistant and Extended – spectrum beta-lactamase producing Escherichia
coli urinary isolates at Queen Rania Al-abdullah Hospital for children, Jordan”. It was a
retrospective study, conducted between May 2012 to September 2012. This study was done to
determine the prevalence and antibiotic resistant patterns of multidrug resistant ESBL producing
E.coli isolates from urine samples of children. The resistant patterns, screening and confirmatory
tests for phenotypic detection of ESBL-producers were studied using the VITEK 2 system
against a set of antibiotics found on the antimicrobial susceptibility extend card AST-EXN8. A
total of 61 urine samples were collected and their resistance patterns were studied. They were
nearly equally infected by both types of E. coli isolates, ESBL-producers 31 (50.8%) and non
ESBL-producers 30 (49.2%). ESBL producing E. coli showed maximum rate of resistance to
cefuroxime and piperacillin (100%), while minimum resistance rate was seen with colistin
(3.2%) and meropenem (0%). ESBL producing isolates were significantly more resistant than
non ESBL producing isolates. MDR was found to be predominant in ESBL producing isolates
which were resistance to at least nine antibiotics.77
13. Imran Khan M, Surui Xu et al. (2020) conducted a study entitled “Assessment of
multidrug resistance in bacterial isolates from urinary tract infected patients”, which was a
prospective study. This study was conducted to evaluate the antimicrobial activity in Urinary
Tract Infections against drugs used in common for treating infection. Sensitivity testing was done
using the Kirby–Bauer technique. A total of 100 urine samples were collected and evaluated.
Infection rate was found to be 33%. Females were found to be 3.17% times more infected than
males. We observed Escherichia coli (E. coli) was observed to be the most frequent and
Pseudomonas aeruginosa (P. aeruginosa) as the least (9.1%). Klebsiella pneumoniae and E.coli
are 2.33 and 7.67 more prevalent than Pseudomonas aeruginosa respectively. Their sensitivity
resulted indicated that Klebsiella pneumoniae and E. coli resistance to the most tested

antimicrobials and Pseudomonas aeruginosa is susceptible to only few of the tested

antimicrobials.78
14. Moini AS, Soltani B et al. (2015) conducted a study entitled “Multidrug resistant
Escherichia coli and Klebsiella pneumoniae isolated from patients in Kashan, Iran”. It was a
prospective, cross-sectional study conducted between February 2012 to March 2013. This study
was conducted to determine the antibiotic resistance patterns and risk factors for MDR E. coli
and Klebsiella pneumoniae. Resistance patterns was evaluated by disc diffusion method and
confirmed by E-test. A total of 250 isolates were collected and resistance to ampicillin-
clavulanic acid, amikacin, gentamycin, ceftriaxone, ceftazidime, ciprofloxacin and imipenem
were evaluated. Among the 250 samples the prevalence of MDR E. coli and Klebsiella
pneumoniae was 50% and 46.6% respectively. Both the strains highly resistance to ampicillin
and resistance to imipenem was not seen. 79
15. Awasthi TK, Pant ND et al. (2015) conducted a study entitled “Prevalence of Multidrug
Resistant bacteria in causing Community Acquired Urinary Tract Infections among the patients
attending outpatient department of Seti Zonal Hospital, Dhangadi, Nepal”. It was a prospective,
cross-sectional study conducted between June 2013 to December 2013. This study was done to
determine the prevalence of multidrug resistant bacteria in community acquired urinary tract
infections. Antimicrobial susceptibility testing was performed by Kirby Bauer disc diffusion
technique. A total of 384 urine samples were collected out of which 98 showed bacterial growth,
among these samples E. coli (53.6%) was found to be the most predominant organism followed
by Klebsiella pneumoniae (21.43%), Pseudomonas aeruginosa (12.24%), Proteus vulgaris
(7.14%), Staphylococcus aureus (4.08%) and Proteus mirabilis (2.04%). Among those 98
isolates, 42 (42.86%) were found to be MDR. 48.08% of the E. coli, 19.05% of the K.
pneumonia, 50% of the P. aeruginosa, 85.71% of the P. vulgaris and 25% of the Staphylococcus
aureus were found to be MDR. No isolates of P. mirabilis were MDR. 80

CHAPTER – 3
MATERIALS AND
METHODS
CHAPTER 3 MATERIALS AND METHODS
3.1 OBJECTIVES OF THE STUDY:
PRIMARY OBJECTIVE:
 To study the antibiotic resistance patterns of bacteria and utilization of antibiotics.
SECONDARY OBJECTIVE:
 To study the etiologies of Community acquired MDR infections.
3.1.1 RATIONALE OF STUDY:
 According to the global action plan on AMR endorsed by WHO, it is important to raise
awareness on AMR through monitoring and research programs in different parts of the
world.81,82 AMR monitoring is critical and has several benefits including providing data on
bacterial resistance rate, helping select appropriate antibiotics and subsequently reduce
AMR rate, reduction in hospitalization rate and treatment costs, and decrease in death
rate.
 The most efficient way to monitor changing drug resistance patterns is surveillance.71
 This study aims to explore the AMR patterns and utilization of antibiotics.
 This could be served as a baseline survey for further interventions to promote the
proper use of antibiotics.

Close monitoring of MDR, is essential to implement effective measures to reduce the
menace of antimicrobial resistance.76
3.2 STUDY DESIGN AND METHODOLOGY:
3.2.1 STUDY DESIGN:
 Retrospective, Observational.
3.2.2 STUDY LOCATION:
 CARE Hospital, Nampally, Hyderabad.
3.2.3 STUDY DURATION:

 The study duration was 6months (August 2019 to January 2020) and the data was collected
retrospectively.
3.2.4 SAMPLE SELECTION:
 Table 11. For Primary Objective
INCLUSION CRITERIA EXCLUSION CRITERIA
 All infectious patients for whom

the antimicrobial susceptibility test
 Patients with multiple infections.
has been performed and the report
was found to be positive.
 Table 12. For Secondary Objective
INCLUSION CRITERIA EXCLUSION CRITERIA
 Positive culture for MDR  Clinical symptoms developing

pathogen. after 48 hours of hospitalization.
 Clinical symptoms related to the  Positive symptoms related to the

MDR pathogen present before the MDR pathogen but with negative
time of admission or within 48hrs cultures.
of admission into the hospital.

3.2.5 SOURCES OF DATA:
Table 13
FOR PRIMARY OBJECTIVE FOR SECONDARY OBJECTIVE
● Patient case files

● Antimicrobial susceptibility test
● Laboratory test reports. reports.
3.2.6 DATA COLLECTION:
● Data was collected using a structured data collection form (APPENDIX 1). Information
collected included demographic characteristics of the patients, admission unit, co-
morbidities, family history, social history, allergies, primary diagnosis or presumed
indication for antibiotic therapy, type of infection, laboratory investigations, antimicrobial
susceptibility test reports results.
3.2.7 SAMPLE SIZE:

 Primary objective : 200
 Secondary objective : 63
3.2.8 DATA ANALYSIS:
 Antimicrobial susceptibility reports are analyzed for the specimen used, the pathogen
identified, sensitivity and resistance pattern.
 Patient case files are analyzed for antibiotics prescribed.
 Continuous variables are represented as mean and standard deviation. Categorical variables
are represented as frequencies and percentages. Data was analyzed using R studio and MS
Excel.

3.2.9 PLAN OF WORK:
Screening articles for topic selection to conduct a study
Title selection and development of research protocol and designing data

collection form
Submitting the study protocol to IEC for approval to carry out the study
Data collection
Data analysis and drawing conclusion
3.3 APPROVAL BY INSTITUTIONAL ETHICS COMMITTEE:
● The study protocol was reviewed and approved by Institutional Ethics Committee, Care
Hospitals, Hyderabad. (Appendix 2).

CHAPTER – 4
RESULTS AND
DISCUSSION
CHAPTER 4 RESULTS AND DISCUSSION
4.1 RESULTS:
The present study was conducted with the aim to determine the patterns of bacterial isolates and
their resistance patterns from various specimens at Care hospital, Nampally, Hyderabad. This study
also attempted to determine the utilization patterns of antibiotics among the patients suffering with
various infections.
Fig.6 Flow chart showing subject inclusion in study
Initially 280 cases were identified

to have infections.
80 cases were excluded as

200 cases were included as - Few were found to be culture negative.
- Samples were found to be culture - Antimicrobial susceptibility reports were not
positive .
available.
186 Gram Negative Isolates
14 Gram Positive Isolates
Out of 280 cases identified to have infections during the study period 200 were included in the
study as the culture test was found to be positive. Exclusion of the remaining cases was either due
to non-availability of the culture reports or a negative culture report.
186 isolates out of the 200 included cases were gram negative and 14 were found to be gram
positive.

DISTRIBUTION OF SUBJECTS BASED ON AGE GROUPS
Majority of the patients in the present study were found to be in the age group of 71-80 years
(51) followed by 51-60 years (48). The Mean Age ± SD was found to be 63.55 ± 14.13 years.
Table 14. Distribution of Subjects Based On Age Groups
AGE GROUP (years) NO. OF SUBJECTS PERCENTAGE(%)

21-30 2 1
31-40 10 5
41-50 24 12
51-60 48 24
61-70 43 21.5
71-80 51 25.5
81-90 22 11
Total 200 100
Figure 7. Graphical Representation of Subjects Based Age Groups

60
NO. OF SUBJECTS
50
40
30
20
10
0
21-30 31-40 41-50 51-60 61-70 71-80 81-90
AGE GROUP

DISTRIBUTION OF SUBJECTS BASED ON GENDER
Among the total culture positive samples, 118 and 82 were male and female patients respectively.
Infections were found to be slightly predominant in male subjects.
Table 15. Distribution of Subjects Based On Gender
GENDER NO. OF SUBJECTS PERCENTAGE(%)
Male 118 59
Female 82 41
Total 200 100
Figure 8. Graphical Representation of Subjects Based on Gender.
41% MALE
59% FEMALE

DISTRIBUTION OF SUBJECTS BASED ON CO-MORBIDITIES
Out of 200 subjects, the most common co-morbidity was Hypertension (59) accounting to 29.5% of
the total subjects, followed by Diabetes mellitus (54) and Chronic kidney disease(39).
Table 16. Distribution of Subjects Based On Co-Morbidities

NO. OF PERCENTAGE
COMORBIDITY SUBJECTS (%)
HTN 59 29.5
DM 54 27
CKD 39 19.5
COPD 27 13.5
CAD 26 13
AFI 20 10
Hypothyroidism 16 8
Stroke 12 6
Anaemia 10 5
OSA 8 4
Asthma 7 3.5
Figure 9. Graphical Representation of Subjects Based On Co-Morbidities.
70
60
50
40
30
20
No. Of Subjects
10
0

DISTRIBUTION OF SUBJECTS BASED ON TYPE OF INFECTIONS
The most common infection in the present study was found to be Urinary tract infection accounting
for 38% of the total subjects, followed by Pneumonia and Sepsis respectively.
Table 17. Distribution of Subjects Based On Type of Infections.
NO. OF
INFECTION PERCENTAGE(%)
SUBJECTS
Urinary Tract Infection 76 38
Pneumonia 52 26
Sepsis 31 15.5
Urosepsis 27 13.5
Sepsis with septic shock 6 3
Fasciitis 3 1.5
Meningitis 2 1
Vaginitis 1 0.5
Total 200 100
Figure 10. Graphical Representation of Subjects Based On Type of Infections.
NO. OF SUBJECTS
Vaginitis
Meningitis
Fasciitis
Sepsis with septic shock
Urosepsis
Sepsis
Pneumonia
Urinary Tract Infection

DISTRIBUTION OF SUBJECTS BASED ON CULTURE SPECIMEN
The specimens included were urine (106), sputum(44), blood (22), pus(7) and others(21) which
include ascitis fluid, BAL fluid, endo-tracheal secretions, swab, pleural fluid, tissue/tracheal
culture.
Table 18. Distribution of Subjects Based On Culture Specimen
CULTURE NO. OF SUBJECTS PERCENTAGE

SPECIMEN (%)
Urine 106 53
Sputum 44 22
Blood 22 11
Pus 7 3.5
Other cultures 21 10.5
Total 200 100
Figure 11. Graphical Representation of Subjects Based On Type of Culture Specimen.
120
NO. OF SUBJECTS
100
80
60
40
20
0
Urine Sputum Blood Pus Other
cultures

DISTRIBUTION OF SUBJECTS BASED ON ORGANISM AND CULTURE SPECIMEN
Out of 200 positive culture isolates 186 were gram negative organisms, 14 were gram positive
organisms. Also one Candida albicans was found which was excluded from the culture positive
isolates.
In this study, the two major isolates were Escherichia coli (94) and Klebsiella spp (49) followed by
Pseudomonas spp (15) and Enterobacter (13).
Table19. Distribution of Subjects Based On Organism and Culture Specimen
ORGANISM CULTURE NO. OF SUBJECTS PERCENTAGE

SPECIMEN
(%)
FOR EACH TOTAL
SPECIMEN
Urine 71
Blood 11
E.coli Sputum 3 94 47
Pus 3
Others 6
Urine 12
Blood 4
Klebsiella Sputum 24 49 24.5
Pus 1
Others 8
Urine 2
Blood 1
Pseudomonas Sputum 7 15 7.5
Pus 1
Others 4
Urine 5
Enterobacter Blood 2 13 6.5
Sputum 6
Enterococcus Urine 11 11 5.5

(Gram positive)

ORGANISM CULTURE NO. OF SUBJECTS PERCENTAGE

SPECIMEN
(%)
FOR EACH TOTAL
SPECIMEN
Urine 4
Citrobacter 9 4.5
Sputum 4
Others 1
Blood 1
Staphylococcus 1 3 1.5
Pus
(Gram positive)
Others 1
Urine 1 2 1
Proteus vulgaris
Pus 1
Blood 1
Acinetobacter 2 1
Others 1
Blood
Alcaligenes 1 1 0.5
Burkholderia Blood 1 1 0.5
Figure 12. Graphical Representation For Organisms Isolated from Samples
E.COLI
KLEBSIELLA
PSEUDOMONAS
ENTEROBACTER
ENTEROCOCCUS
CITROBACTER
STAPHYLOCOCCUS
PROTEUS VULGARIES
ACINETOBACTER
ALCALIGENES
BURKHOLDERIA

ANTIMICROBIAL RESISTANCE PATTERNS OF GRAM NEGATIVE BACTERIA

RESISTANCE %)
Antibiotic susceptibility patterns of gram negative organisms are shown in the table 20.
The susceptibility pattern of Escherichia coli, which is the predominant isolate among gram
negative organisms exhibit most resistance to ampicillin (96%) followed by ceftriaxone (93%) and
cefpodoxime (92%).
Klebsiella spp. shows maximum resistance to ampicillin (96%) followed by amoxicillin (57%) and
ceftriaxone (54%). Pseudomonas spp. exhibit high resistance to ampicillin (100%) followed by
cefpodoxime (79%) and amoxicillin (64%).
Enterobacter spp. shows high resistance to ceftriaxone (100%) followed by cefpodoxime (91%) and
amoxicillin (80%).
Another gram negative organism Citrobacter exhibited maximum resistance to cefpodoxime (89%),
and ampicillin (89%) followed by nitrofurantoin (75%).
Table 20. Antimicrobial Resistance Patterns of Gram Negative Bacteria (Resistance %)
Alcaligens (%)
Acenitobacter
Pseudomonas
Enterobacter
Burkholeria
E.Coli (%)
Citrobacter
Proteus(%)
Klebsiella
(%)
(%)
(%)
(%)
S. DRUG
(%)
(%)
No
1 Cefoxitin 42(46) 26(53) 8(57) 9(75) 6(67) 0 2(100) - 1(100)

2 Cefepime 75(83) 25(53) 5(33) 9(69) 6(67) 0 2(100) 0 1(100)
3 Ceftazidime 63(75) 21(49) 6(40) 7(64) 6(67) 0 2(100) 0 1(100)
4 Ceftazidime/ 35(42) 15(35) 4(29) 6(60) 3(33) 0 2(100) - 1(100)
Clavulanate
5 Cefpodoxime 77(92) 24(51) 11(79) 10(91) 8(89) 0 2(100) - 1(100)
6 Cefoperazone/ 18(22) 14(33) (18) 5(45) 2(22) 0 1(50) - 0
Sulbactam
7 Ceftriaxone 76(93) 22(54) 7(50) 10(100) 6(67) 0 2(100) - 0
8 Cefotaxime 20(83) 5(28) 2(29) 1(25) 0 0 0 - -
9 Cefazolin 12(52) 5(28) 1(14) 2(50) 0 0 0 - -
10 Cotrimoxazole 45(60) 6(30) 2(29) 1(17) 1(33) 0 0 0 -
11 Penicillin 5(50) 2(22) 0 0 - 0 0 - -
12 Piperacillin/ 26(28) 15(32) 0 4(31) 2(22) 0 2(100) 0 0
Tazobactam

13 Ampicillin 87(96) 47(96) 14(100) 10(77) 8(89) 0 2(100) - 1(100)

14 Oxacillin 9(50) 0 0 0 1(50) 0 0 - -
15 Amoxicillin/ 27(68) 26(57) 9(64) 8(80) 5(71) 0 2(100) - 1(100)
Clavulanate
16 Ciprofloxacin 77(86) 27(55) 4(26) 8(62) 6(67) 0 2(100) 0 1(100)
17 Ofloxacin 68(81) 19(46) 5(36) 8(73) 4(44) - 2(100) - 1(100)
18 Levofloxacin 13(54) 6(34) 3(38) 2(50) 0 0 - 0 -
19 Gentamicin 25(27) 12(24) 2(13) 4(31) 3(33) 0 2(100) 1 -
(100)
20 Amikacin 14(15) 11(23) 1(7) 3(23) 1(13) 0 2(100) 0 1(100)
21 Meropenem 8(9) 6(13) 1(7) 3(23) 1(11) 0 2(100) 0 0
22 Imipenem 8(9) 7(14) 1(7) 2(17) 1(11) - 2(100) 0 0
23 Vancomycin 0 0 0 - - - - - -
24 Clindamycin 0 0 0 - - - - - -
25 Erythromycin 0 0 0 - - - - - -
26 Tetracycline 0 0 0 0 0 - - - -
27 Nitrofurantoin 8(12) 3(21) 2(33) 1(17) 3(75) 0 - - -
28 Aztreonam 47(57) 22(54) 3(20) 5(45) 4(44) 0 2(100) 0 1(100)
29 Linezolid 3(18) 1(10) 1(17) 0 0 - - - -
30 Colistin 0 0 0 0 0 - 0 0 1(100)
31 Tigecycline 2(6) 0 0 1(11) 0 - 0 0 0
32 Rifampin - 0 0 - - - - - -
33 Teicoplanin - - - - - - - - -
34 Novobiocin - - - - - - - - -
35 Fusidic acid - - - - - - - - -
‘0’ Indicates no resistance for the particular drug by the organism.

‘-’ Indicates samples are not tested for the particular drug.
% Resistance is calculated by R/T x 100
R = Number of samples (of the particular organism) resulted as resistance to the drug.
T = Total number of samples (of the particular organism) tested.
ANTIMICROBIAL RESISTANCE PATTERNS OF GRAM POSITIVE BACTERIA
(RESISTANCE %)
Among gram positive isolates, Enterococcus spp. is mostly resistant to ciprofloxacin (91%)
followed by levofloxacin (82%) and tetracycline (82%). Another gram positive isolate,
Staphylococcus spp. shows maximum resistance to penicillin (100%), ampicillin (100%),
erythromycin (100%), followed by ciprofloxacin (67%) (as shown in table 21)

Based on the results of our study, infections caused by gram negative organisms (93%) is more
when compared to gram positive organisms (7%).
Table 21. Antimicrobial Resistance Patterns of Gram Positive Bacteria (Resistance %)
S. DRUG Enterococcus(%) Staphylococcus(%)

NO
1 Ciprofloxacin 10 (91) 2 (67)
2 Gentamicin 8 (80) 1 (33)
3 Ampicillin 6 (55) 3 (100)
4 Penicillin 6 (55) 3 (100)
5 Amoxicillin/ Clavulanate 6 (60) 1 (33)
6 Oxacillin 1 (50) 1 (33)
7 Rifampin 1 (100) 0
8 Levofloxacin 9 (82) 0
9 Erythromycin - 3 (100)
10 Tetracycline 9 (82) 0
11 Ofloxacin 1 (50) 0
12 Amikacin 1 (50) 0
13 Clindamycin 0 1(33)
14 Nitrofurantoin 2 (18) 0
15 Teicoplanin 2 (18) 0
16 Fusidic acid - 1 (50)
17 Cefoxitin 0 0
18 Cefepime 0 0
19 Ceftazidime 0 0
20 Ceftazidime/ Clavulanate 0 0
21 Cefpodoxime 0 0
22 Cefoperazone/ Sulbactam 0 0
23 Ceftriaxone 0 0
24 Cefotaxime 0 0
25 Cefazolin 0 0
26 Cotrimoxazole 0 0
27 Piperacillin/ Tazobactam 0 0
28 Meropenem 0 0
29 Imipenem 0 0
30 Vancomycin 0 0
31 Aztreonam 0 0
32 Linezolid 0 0
33 Colistin 0 0
34 Tigecycline 0 0
35 Novobiocin 0 0

UTILISATION OF ANTIBIOTICS
AVERAGE NUMBER OF ANTIBIOTICS PRESCRIBED
Average number of antibiotics per prescription is the ratio of the total number of antibiotics
prescribed by the total number of prescriptions.
Table 22. Average Number of Antibiotics Prescribed
Total number of antibiotics prescribed 445
Total number of prescriptions 200
Average number of antibiotics per prescription 2.22
UTILISATION PATTERNS OF ANTIBIOTICS PRESCRIBED
The utilization patterns of antibiotics is represented in the table 23.
In this study, cephalosporins (174) was most frequently prescribed class of antibiotics followed by
carbapenems (56), penicillins (53) and fluoroquinolones (42).
Ceftriaxone (42%) was was found to be the most frequently prescribed antibiotic followed by
cefoperazone/sulbactam (33.5%) and meropenem (25.5%) in the current study.

Table 23. Utilisation Patterns of Antibiotics Prescribed
CLASS (TOTAL) DRUGS NO. OF %

PRESCRIPTIONS
Piperacillin/Tazobactum 30 30/200×100 = 15
Penicillins (53) Amoxicillin/Clavulanate 21 10.5
Flucloxacillin 2 1
Ceftriaxone 84 42
Cefoperazone/Sulbactam 67 33.5
Ceftazidime/Tazobactum 8 4
Cefuroxime 8 4
Cephalosporins Cefixime 2 1
(174) Ceftazidime/Clavulanate 1 0.5
Cefaperazone/Tazobactam 1 0.5
Cefixime/Clavulanate 1 0.5
Ceftazidime 1 0.5
Ceftazidime/Avibactum 1 0.5
ß-Lactamase Inhibitor Sulbactam 2 1

(2)
Sulfonamides (2) Cotrimoxazole 2 1
Tetracyclines (8) Minocycline 5 2.5
Doxycycline 3 1.5
Macrolides (30) Clarithromycin 20 10
Azithromycin 10 5
Aminoglycosides (7) Amikacin 7 3.5

Ciprofloxacin 16 8
Levofloxacin 13 6.5
Fluoroquinolones
Ofloxacin 12 6
(42)
Norfloxacin 1 0.5
Glycopeptide (6) Vancomycin 5 2.5

Teicoplanin 1 0.5
Carbapenem Meropenem 51 25.5
(56) Ertapenem 5 2.5
Nitroimidazole (6) Metronidazole 5 2.5
Tinidazole 1 0.5
Lincomycin (20) Clindamycin 20 10
Rifamycins (9) Rifaximin 5 2.5
Rifamycin 4 2
Polymyxins (14) Colistin 7 3.5
Polymyxin 7 3.5
Nitrofurans (6) Nitrofurantoin 6 3
Oxazolidinones (3) Linezolid 3 1.5
Glycylcyclines (2) Tigecycline 2 1
Phosphonic Acid Fosfomycin 5 2.5
Derivatives (5)
Figure 13. Graphical Representation Of Most Commonly Prescribed Antibiotic Classes.
Cephalosporins
Carbapenem
Penicillins
Fluoroquinolones
Macrolides
Lincomycin
Others

SINGLE VS MULTIPLE ANTIBIOTIC THERAPY
Single antibiotic therapy (33%) was found to be the most commonly prescribed therapy followed
by three drug therapy (26%) and two drug therapy (24.5%) in the present study.
Table 24. Single Vs Multiple Antibiotic Therapy
DRUG THERAPY NO. OF PRESCRIPTIONS PERCENTAGE

PRESCRIBED (%)
Single drug therapy 66 66/200×100 =33
MULTIDRUG THERAPY
2 drug therapy 49 24.5
3 drug therapy 52 26
4 drug therapy 18 9
5 drug therapy 8 4
The most commonly prescribed treatment for infections was single antibiotic therapy(66),
followed by three drug therapy(52).

Figure 14. Graphical Representation of Total Number of Antibiotics per Prescription.
70
60
50
40
30
20 NO. OF
10
PRESCRIPTIONS
Table 25. Single Vs Multiple Antibiotic Therapy With Drugs

DRUG THERAPY
PRESCRIBED
(Total No. Of NO. OF
Prescriptions with DRUGS PRESCRIPTIONS %
the corresponding
therapy)
23/200
Cefoperazone/Sulbactum 23 ×100=
11.5
Ceftriaxone 22 11
Meropenem 8 4
Amoxicillin/Clavulanic Acid 2 1
Single Drug Ceftazidime/Tazobactum 1 0.5
Therapy Cefixime/Clavulanic Acid 1 0.5
Cefuroxime 1 0.5
Cefepime/Tazobactum 1 0.5
Ceftazidime/Avibactum 1 0.5
Clarithromycin 1 0.5
Ciprofloxacin 1 0.5
Vancomycin 1 0.5
Tinidazole 1 0.5
Nitrofurantoin 1 0.5
Piperacillin/Tazobactum 1 0.5

MULTIPLE DRUG THERAPY

Meropenem, 5 2
Cefaperazone/Sulbactum
Amoxicillin/Clavulanic Acid, Clarithromycin 4 2
Ceftriaxone, Cefoperazone/Sulbactum. 4 2
Meropenem, Clindamycin 3 1.5
Cefoperazone/Sulbactum, 3 1.5
Amoxicillin/Clavulanic Acid
Levofloxacin, Meropenem 2 1
Cefoperazone/Sulbactum, Clarithromycin 2 1
Two Drug Cefoperazone/Sulbactum, 2 1
Therapy Ciprofloxacin
(49) Ceftriaxone, Piperacillin/Tazobactum 2 1
Piperacillin/Tazobactum, Clindamycin 2 1
Ceftriaxone, Meropenem 2 1
Cefoperazone/Sulbactum, Azithromycin 2 1
Ciprofloxacin, Azithromycin 1 0.5
Ceftriaxone, Cotrimoxazole 1 0.5
Ceftriaxone, Nitrofurantoin 1 0.5
Cefoperazone/Sulbactum, Cefuroxime 1 0.5
Ceftriaxone,Azithromycin 1 0.5
Piperacillin/Tazobactum, 1 0.5
Cefoperazone/Sulbactum
Cefoperazone/Sulbactum, Ofloxacin 1 0.5
Ceftazidime/Clavulanate, 1 0.5
Cefoperazone/Tazobactum
Nitrofurantoin
Ceftriaxone, 1 0.5
Metronidazole
Amikacin, Meropenem 1 0.5
Cefoperazone/Sulbactum, Ertapenem 1 0.5
Ceftriaxone, Cefepime 1 0.5
Levofloxacin, Ceftriaxone 1 0.5
Ciprofloxacin, Clarithromycin 1 0.5
Rifamycin, Ceftriaxone 1 0.5

DRUG THERAPY
PRESCRIBED
Prescriptions with the DRUGS PRESCRIPTIONS %
corresponding therapy)
Ceftriaxone, Cefoperazone/Sulbactum, 3 1.5
Meropenem
Clarithromycin
Ceftriaxone, Amoxicillin/Clavulanate, 3 1.5
Cefoperazone/Sulbactum, Doxycycline, 2 1
Ceftriaxone
Ceftriaxone, Ceftazidime/Tazobactum, 2 1
Ofloxacin
Piperacillin/Tazobactum, Meropenem, 2 1
Tigecycline
Piperacillin/Tazobactum, Clindamycin, 2 1
Three Drug Therapy Levofloxacin
(52) Piperacillin/Tazobactum, Clindamycin, 2 1
Ciprofloxacin
Ceftriaxone, Ceftazidime/Tazobactum, 2 1
Ofloxacin
Ceftriaxone, Levofloxacin, Meropenem 2 1
Doxycycline, Meropenem, Ertapenem 2 1
Clarithromycin, Ceftriaxone
Amoxicillin/Clavulanic Acid, 1 0.5
Clarithromycin, Levofloxacin
Ceftriaxone, Cefixime, 1 0.5
Amoxicillin/Clavulanic Acid
Ciprofloxacin, Nitrofurantoin, 1 0.5
Ceftriaxone, Sulbactum, 1 0.5
Colistin
Cefoperazone/Sulbactum, Ertapenem,
Cotrimoxazole 1 0.5
Cefoperazone/Sulbactum, Polymixin,
Fosfomycin 1 0.5
Levofloxacin,
Amoxicillin/Clavulanic Acid, Ceftriaxone 1 0.5
Meropenem, Ertapenem,
Cefoperazone/Sulbactum 1 0.5
Cefoperazone/Sulbactum,
Ciprofloxacin, Clindamycin 1 0.5

DRUG THERAPY
PRESCRIBED
corresponding
therapy)
Ceftriaxone, Amoxicillin/Clavulanic Acid,
Levofloxacin 1 0.5
Cefoperazone/Sulbactum, Fluoxacillin,
Ofloxacin 1 0.5
Colistin, Sulbactum,
Cefoperazone/Sulbactum 1 0.5
Cefepime/Tazobactum, Vancomycin,
Meropenem 1 0.5
Ceftriaxone, Azithromycin,
Levofloxacin 1 0.5
Cefaperazone/Sulbactum, Ciprofloxacin,
Fluocloxacillin 1 0.5
Three Drug
Therapy Ceftriaxone, Meropenem,
(52) Ertapenem 1 0.5
Cefepime, Ceftazidime/Tazobactum,
Ciprofloxacin 1 0.5
Ceftriaxone, Cefaperazone/Sulbactum,
Ceftazidime/Tazobactum 1 0.5
Cefuroxime,
Cefaperazone/Sulbactum,
Ciprofloxacin 1 0.5
Meropenem, Polymyxin,
Linezolid 1 0.5
Ceftriaxone, Clarithromycin, Ofloxacin 1 0.5
Cefuroxime, Amikacin,
Norfloxacin 1 0.5
Amoxicillin/Clavulanic Acid,
Piperacillin/Tazobactum,
Clindamycin 1 0.5
Ceftazidime/Tazobactum, Clindamycin,
Amoxicillin/Clavulanic Acid 1 0.5
Piperacillin/tazobactum,
Clarithromycin, Amoxicillin/Clavulanic Acid 1 0.5
Meropenem, Ertapenem, Polymixin B
1 0.5

DRUG THERAPY
PRESCRIBED
corresponding
therapy)
Cefaperazone/Sulbactum, 3 1.5
Meropenem, Ertapenem, Colistin
Ceftriaxone, Cefepime/Tazobactum, 2 1
Piperacillin/Tazobactum, Azithromycin
Cefaperazone/Sulbactum, 2 1
Amoxicillin/Clavulanicacid,
Meropenem, Amikacin
Ceftriaxone, Amikacin, 2 1
Ceftazidime, Piperacillin/Tazobactum
Ceftriaxone, Rifaximin, 1 0.5
4 Drug Therapy Cefoperazone/Sulbactum, Nitrofurantoin
(18) Colistin, Meropenem, 1 0.5
Cefuroxime, Cefuroxime/Clavulanic Acid,
Ceftriaxone, Clarithromycin, 1 0.5
Cefuroxime, Amoxicillin/Clavulanic Acid
Ceftriaxone, Cefaperazone/Sulbactum, 1 0.5
Colistin, Sulbactum
Ceftriaxone, Amikacin, 1 0.5
Piperacillin/Tazobactum, Clindamycin
Meropenem, Linezolid, 1 0.5
Cefepime/Tazobactum,
Cefaperazone/Sulbactum
Ceftriaxone, Cefaperazone/Sulbactum, 1 0.5
Meropenem, Cefuroxime
Amoxicillin/Clavulanic acid,. Ceftriaxone, 1 0.5
Levofloxacin, Cefaperazone/Sulbactum
Azithromycin, Cefepime/Tazobactum
Clindamycin, Piperacillin/Tazobactum,. 3 1.5
Amoxicillin/Clavulanic Acid, Ceftriaxone,
Ciprofloxacin
5 Drug Therapy Ceftriaxone, Clarithromycin, 2 1
(8) Cefepime/Tazobactum,
Piperacillin/Tazobactum, Azithromycin
Cefaperazone/Sulbactum, Meropenem, 1 0.5
Doxycycline,
Clindamycin, Ceftazidime/Tazobactum
Ceftriaxone, Cefepime/Tazobactum, 1 0.5
Meropenem,
Nitofurantoin, Linezolid
Meropenem, Piperacillin/Tazobactum, 1 0.5
Clindamycin,
Polymyxin, Minocycline

DRUG THERAPY
PRESCRIBED NO. OF
(Total No. Of DRUGS PRESCRIPTION %
Prescriptions with the S
corresponding
therapy)
6 Drug Therapy Meropenem, Polymyxin, Clindamycin 1 0.5
(1) Metronidazole, Fosfomycin, Minocycline.
8 Drug Therapy Ceftriaxone, Piperacillin/Tazobactum, 1 0.5
(1) Amoxicillin/Clavulanic Acid
Ofloxacin, Clindamycin, Meropenem
Teicoplanin, Polymyxin

ETIOLOGIES OF COMMUNITY ACQUIRED MULTI DRUG

RESISTANT INFECTIONS
Community Acquired Infection:
Community acquired infection (CAI) is defined as the infection which is detected with in 48 hours
of hospital admission in patients without previous contact with healthcare service. 85
In the present study, 63 community acquired MDR cases were obtained.
DISTRIBUTION OF MDR SUBJECTS BASED ON AGE GROUPS
Majority of the MDR patients were found to be in the age group of 51-70 years (29) followed
by 71-90 years (26). Mean age ± SD = 66.53 ± 15.50
Table 26. Distribution Of MDR Subjects Based On Age Groups
AGE GROUP (years) NO. OF SUBJECTS PERCENTAGE(%)

11-30 2 3.17
31-50 5 7.93
51-70 29 46.03
71-90 26 41.26
91-110 1 1.58
TOTAL 63 100
Figure 15. Graphical representation for distribution of MDR subjects based on age groups
35
30
25
20
15 No. Of subjects
10
5
0
11-30 31-50 51-70 71-90 91-110

DISTRIBUTION OF MDR SUBJECTS BASED ON GENDER
Among the total MDR samples, 36 and 27 were male and female patients respectively.MDR
Infections were found to be slightly predominant in male.
Table 27. Distribution of MDR Subjects Based on Gender
GENDER NO. OF SUBJECTS PERCENTAGE

(%)
Male 36 57.14
Female 27 42.85
Total 63 100
Figure 16. Graphical Representation for Distribution of MDR Subjects Based on Gender.
NO. OF SUBJECTS
MALE
FEMALE

ETIOLOGIES OF COMMUNITY ACQUIRED MDR INFECTIONS
All the MDR isolates were gram negative organisms. The major isolates in this study were E.coli
(35), Pseudomonas (11), Klebsiella (11) respectively.
Table 28. Etiologies of Community Acquired MDR Infections
S.No Organism Sample For each Total no. of

specimen subjects
Urine 31
1 E.coli Pus 2 35
Sputum 1
Others 1
2 Urine 5
Pseudomonas Sputum 3 11
Others 3
3 Urine 5
Klebsiella Sputum 5 11
Others 1
4 Citrobacter Sputum 1
Others 2 3
5 Enterobacter Urine 1
Sputum 1 2
6 Proteus vulgaris Urine 1 1
TOTAL 63
Figure 17. Graphical Representation for Organisms isolated from MDR samples.
E.COLI
PSEUDOMONAS
KLEBSIELLA
CITROBACTER
ENTEROBACTER
PROTEUS
VULGARIS

ANTIBIOTIC SUSCEPTIBILITY PATTERNS FOR MDR BACTERIA
 E. coli was the predominant isolate among the gram negative MDR bacteria followed by
Pseudomonas spp. and Klebsiella spp. The MDR gram negative isolates exhibited higher resistance
to ampicillin and cefpodoxime.
 The susceptibility pattern of Escherichia coli, which is the predominant isolate among gram
negative organisms exhibited most resistance to ampicillin (100%), cefpodoxime (100%) and
ciprofloxacin (100%). Maximum sensitivity was exhibited to nitrofurantoin (93.54%), meropenem
(88.57%) and imipenem (88.57%).
 Pseudomonas spp. shows maximum resistance to ampicillin (100%) followed by cefpodoxime
(90.9%) and cefoxitin (90.9%). High sensitivity was shown to amikacin (90.9%) followed by
meropenem (80.81%) and imipenem (80.81%).
 Klebsiella spp. exhibits high resistance to ampicillin (100%) followed by cefpodoxime (100%) and
ciprofloxacin (100%). Organism exhibits high sensitivity to gentamicin (72.72%) and amikacin
(72.72%) followed by meropenem (63.63%) and imipenem (63.63%).
Table 29. Antibiotic Susceptibility Patterns for MDR Bacteria
S. E.COLI PSEUDOMONAS KLEBSIELLA

N DRUG
O R(%) S(%) R(%) S(%) R(%) S(%)
1. Cefoxitin 13(37.14) 22(62.85) 10(90.9) 1(9.09) 9(81.81) 2(18.18)
2. Cefepime 34(97.14) 1(2.85) 3(27.27) 8(72.72) 9(81.81) 2(18.18)
3. Ceftazidime 33(94.28) 2(5.71) 5(45.45) 6(54.54) 9(81.81) 2(18.18)
4. Ceftazidime/clavulanate 10(28.57) 25(71.42) 3(27.27) 8(72.72) 6(54.54) 5(45.45)
5. Cefpodoxime 35(100) 0(0) 10(90.9) 1(9.09) 11(100) 0(0)
6. Cefoperazone/sulbactam 8(22.85) 27(77.14) 5(45.45) 6(54.54) 5(45.45) 6(54.54)
7. Ceftriaxone 32(91.42) 3(8.57) 8(72.72) 3(27.27) 10(90.9) 1(9.09)
8. Piperacillin/tazobactam 9(25.71) 26(74.28) 3(27.27) 8(72.72) 6(100) 0(0)
9. Ampicillin 35(100) 0(0) 11(100) 0(0) 11(100) 0(0)
10. Amoxicillin/clavulanate 4(11.42) 31(88.57) 5(45.45) 6(54.54) 6(54.54) 5(45.45)
11. Ciprofloxacin 35(100) 0(0) 7(63.63) 4(36.36) 10(100) 0(0)
12. Ofloxacin 32(94.11) 2(5.88) 4(40) 6(60) 8(72.72) 3(27.27)
13. Gentamicin 17(48.57) 18(42.85) 3(27.27) 8(72.72) 3(27.27) 8(72.72)
14. Amikacin 6(17.14) 29(82.85) 1(9.09) 10(90.9) 3(27.27) 8(72.72)
15. Meropenem 4(11.42) 31(88.57) 2(18.18) 9(81.81) 4(36.36) 7(63.63)
16. Imipenem 4(11.42) 31(88.57) 2(18.18) 9(81.81) 4(36.36) 7(63.63)
17. Nitrofurantoin 2(6.45) 29(93.54) 4(80) 1(20) 4(80) 1(20)
18. Aztreonam 28(82.35) 6(17.64) 3(27.27) 8(72.72) 9(81.81) 2(18.18)
19. Cotrimoxazole 22(75.86) 7(24.13) 4(100) 0(0) 3(100) 0(0)

‘0’ Indicates no resistance / sensitivity for the particular drug by the organism.
‘-’ Indicates samples are not tested for the particular drug.
% Resistance is calculated by R/T x 100
R = Number of samples (of the particular organism) resulted as resistance to the drug.
% Sensitivity is calculated by S/T x 100
S = Number of samples (of the particular organism) resulted as sensitive to the drug.
S. CITROBACTER ENTEROBACTER PROTEUS

NO DRUG VULGARIS
R(%) S(%) R(%) S(%) R(%) S(%)

1. Cefoxitin 2(66.66) 1(33.33) 2(100) 0(0) 1(100) 0(0)
2. Cefepime 1(33.33) 2(66.66) 1(50) 1(50) 0(0) 1(100)
3. Ceftazidime 1(33.33) 2(66.66) 2(100) 0(0) 0(0) 1(100)
4. Ceftazidime/clavulanate 1(33.33) 2(66.66) 1(50) 1(50) 0(0) 1(100)
5. Cefpodoxime 3(100) 0(0) 2(100) 0(0) 1(100) 0(0)
6. Cefoperazone/sulbactam 0(0) 3(100) 2(100) 0(0) 0(0) 1(100)
7. Ceftriaxone 2(66.66) 1(33.33) 2(100) 0(0) 1(100) 0(0)
8. Piperacillin/tazobactam 0(0) 3(100) 1(50) 1(50) 0(0) 1(100)
9. Ampicillin 3(100) 0(0) 2(100) 0(0) 1(100) 0(0)
10. Amoxicillin/clavulanate 2(100) 0(0) 2(100) 0(0) - -
11. Ciprofloxacin 2(66.66) 1(33.33) 2(100) 0(0) 1(100) 0(0)
12. Ofloxacin 0(0) 3(100) 2(100) 0(0) 1(100) 0(0)
13. Gentamicin 1(50) 1(50) 1(50) 1(50) 0(0) 1(100)
14. Amikacin 1(33.33) 2(66.66) 0(0) 2(100) 0(0) 1(100)
15. Meropenem 0(0) 3(100) 0(0) 2(100) 0(0) 1(100)
16. Imipenem 0(0) 3(100) 0(0) 2(100) 0(0) 1(100)
17. Nitrofurantoin 0(0) 1(100) 2(100) 0(0) 1(100) 0(0)
18. Aztreonam 3(100) 0(0) - - 0(0) 1(100)
19. Cotrimoxazole - - - - - -
The antibiotics use in prescriptions were governed by Antibiotic Committee. Whenever they
prescribed High End or Reserve Antibiotics to any patient, the prescriptions were audited by
committee for its justification for use, and if not justified it will be discussed with the clinician and
changes in antibiotic is done accordingly.

4.2 DISCUSSION
RESISTANCE PATTERNS:
Our observational study has shown very high levels of resistance to antimicrobial agents
belonging to different classes, for both gram positive and gram negative bacteria. Antibiotic
resistance of bacteria is a significant threat all over the world. But for developing countries like
India this is an even greater public health problem. This is because India has one of the highest
burden of bacterial diseases in the world and thus, antibiotics have a significant role in reducing
mortality and morbidity in the country. 69
Most of the patients with infections were found to be elderly i.e in the age group of 70-80 years,
followed by 51-60 years. This was found to be different than a study conducted in India 84 where
majority of patients belonged of the age group 61-70 years (28.1%), followed by 41-50 years.
In the present study it was observed that infections were more common in the male gender (118)
which is quite similar to the studies conducted by Ramanath K V et al. (2019),84 Rudrajit Paul et al.
(2017) 69 and R.S Parihar et al. (2018) 67.
Out of 200 positive culture isolates, gram negative (186) isolates were predominant in the present
study when compared to gram positive isolates. This was found to be consistent with similar
studies conducted earlier including Nazneen et al. (2016)68, Rudrajit Paul et al. (2017)69 and Viral
Vadwai et al. (2015)71, but in another study conducted by R.S Parihar et al. (2018) 67 gram positive
isolates have taken over gram negative isolates.
Among gram negative isolates, most commonly isolated organism was found to be E.coli, which is
consistent with previous studies conducted by Nazneen et al. (2016) 68, Rudrajit Paul et al. (2017)69.
In one of the earlier studies Acinetobacter baumannii was observed as predominant gram negative
oraganism by Nidhi Bhardwaj et al. (2018). 70
Most commonly isolated organism among gram positive isolates in the present study was
Enterococcus spp., while in other studies by Nazneen et al. (2016) 68, Rudrajit Paul et al. (2017)69
and Viral Vadwai et al.(2015)71 it was observed as Staphylococcus species.

According to the studies conducted by Rudrajit Paul et al. (2017) 69 and Moremi N et al. (2016)66
blood infections followed by urinary tract infections were found to be the common infections.
The most frequent organisms found in urine and blood sample were E.coli followed by Klebsiella
where as commonly isolated organisms in sputum were Klebsiella followed by Pseudomonas and
Enterobacter.
With regard to urinary tract infections which is the most common infection in this analysis, E. coli
was found to be the most frequently isolated pathogen and this finding was consistent with the
findings of Moremi N et al. (2016). 66
Staphylococcus aureus and Klebsiella pneumoniae were commonly isolated from bloodstream
infections.
E.coli being the predominant organism of the study showed maximum resistance to ampicillin
while in the findings by Nazneen et al. (2016) 68 it is 3rd generation cephalosporins and in the study
conducted by Rudrajit Paul et al. (2017) 69 it is penicillin and its congeners when compared to other
drugs.
Enterococcus spp. showed high resistance to ciprofloxacin followed by levofloxacin and

tetracycline while in study made by Nazneen et al. (2016) 68 it is erythromycin and in the findings
depicted by Rudrajit Paul et al. (2017) 69 high resistance was shown to penicillin and its congeners,
4th generation cephalosporins, floroquinolones and macrolides.
Staphylococsus sps. has shown resistance to penicillin, ampicillin erythromycin and ciprofloxacin.
There are many reasons for this rapid rise of antibiotic resistance in India. One reason is the
prevailing trend of prescribing antibiotics for different symptoms like fever, where antibiotics are
not indicated. This trend is present in both urban and rural settings and thus, antibiotic resistant
bacteria have been isolated from even remote localities. 69

UTILISATION OF ANTIBIOTICS:
The average number of antibiotics per prescription in this study was 2.22, which exceeded WHO
limit of 1.6-1.8. 83 While in the study conducted by Dzelamonyuy E Chem et al. (2018) 74 the
average number of antibiotics per prescription was found to be 1.14 and in the study conducted by
Worku F et al. (2018) 73 the average number of antibiotics per prescription was found to be 2.0.
In this study, the most frequently prescribed classes of antibiotics were cephalosporins (174),
penicillins (53) , fluoroquinolones (42) and carbapenems (56). While in the study conducted by
Yimenu DK et al. (2019)75 penicillin (217) was the most frequently prescribed category of
antibiotics followed by macrolides (84) and in the study conducted by Worku F et al. (2018)73 the
prescription pattern analysis showed that penicillins were most commonly prescribed accounting to
51.9%, followed by fluoroquinolones (18.3%) and sulfonamides (11.2%).
Considering specific antibiotics, ceftriaxone (42%) followed by cefoperazone/sulbactam (33.5%)

and meropenem (25.5%) were the most frequently prescribed in the current study. While in the
study conducted by Worku F et al. (2018)73 the amoxicillin prescribing rate was high which is
51.9%, followed by ciprofloxacin (13.6%), cotrimoxazole (11.2%) and in the study conducted by
Dzelamonyuy E Chem et al. (2018)74 most commonly prescribed was amoxicillin (29.29%),
followed by cotrimoxazole (19.08%) and metronidazole (15.59%).
COMMUNITY ACQUIRED MDR STUDY:
Recent studies have shown multi-drug resistant organisms emerging from all parts of India. This
trend has been documented for both gram positive and gram negative bacteria. 69
In the present study, 63 community acquired MDR cases were obtained from the nursing
department. Majority of the MDR patients were found to be in the age group of 51-70 years (29)
followed by 71-90 years (26).
E.coli was found to be the most predominant community acquired MDR pathogen followed by
Klebsiella spp. and Pseudomonas spp. Similar findings were observed in previous study done by

Awasthi TK et al. (2015), 80 where as in the study done by Imran Khan M et al. (2020) it was found
that E. coli as the most frequent and Pseudomonas aeruginosa as the least. 78
In our study E. coli and Pseudomonas spp. exhibited high resistance to ampicillin (100%). These
results were in the agreement with the study conducted by Moini AS et al. (2015). 79 In our study
not only E. coli and Pseudomonas spp. which exhibited high resistance to ampicillin but also all
other MDR pathogens showed high resistance to ampicillin.
In the present analysis, E.coli was found to be highly susceptible to nitrofurantoin (93.54%) while
in Imran Khan M et al. (2020) it was observed as amikacin (52.2%). Pseudomonas spp. exhibited
high sensitivity to amikacin (90.9%) followed by meropenem (80.81%) and imipenem (80.81%) in
this study, where as it is amikacin (100%), ceftriaxone (100%) and Piperacillin/tazobactum (100%)
in the study by Imran Khan M et al. (2020). 78
Several studies showed inappropriate antibiotic usage was 20-50% and 70% of the bacteria that
cause infections in hospitals are resistant to at least one of the most commonly used antibiotic.
Some organisms are resistant to all approved antibiotics and can only be treated with experimental
and potentially toxic drugs. The present situation is showing that many of the second and third line
agents are turning to be ineffective in clinical settings because of mutation in bacterial or host gene.
The slow pace antimicrobial new molecules introduced into the market inadequately leading to
increasing the thirst of antibiotics globally. 84

CHAPTER – 5
Conclusions
CHAPTER 5 CONCLUSION
5. CONCLUSION
The study suggests that the rational use of antibiotics should be given great importance for better
healthcare outcomes. Antimicrobial susceptibility testing helps in determining the resistance and
sensitivity pattern, which further helps in providing effective treatment. This study also gives
information about the common resistant organism in different diseases.
Major findings of the present study are:
 E.coli,which is the predominant isolate among gram negative organisms exhibited a

higher resistance to ampicillin followed by ceftriaxone and cefpodoxime.
 Klebsiella spp. has shown maximum resistance to ampicillin followed by amoxicilin and
ceftriaxone.
 Pseudomonas spp. exhibited high resistance to ampicillin followed by cefpodoxime and
amoxicillin.
 Enterobacter spp. shows high resistance to ceftriaxone followed by cefpodoxime and
amoxicillin.
 Among common gram positive isolates, Enterococcus spp. is mostly resistant to
ciprofloxacin followed by levofloxacin and tetracycline. Another gram positive isolate,
Staphylococcus spp. shows maximum resistance to pencillin, ampicillin, erythromycin,
followed by ciprofloxacin.
 It was observed that frequently isolated organisms were found to be resistant to most
commonly used drugs such as ampicillin, cefpodoxime, amoxicillin and ceftriaxone
which is alarming and calls for a surveillance of HAIs and community infections to
establish the source and transmission pathways.
 The most commonly prescribed antibiotic was found to be ceftriaxone followed by
cefoperazone/sulbactam, meropenem, piperacillin/tazobactum, amoxicillin/clavulanate
and clindamycin.
 Commonly prescribed antibiotic, ceftriaxone which was one the most prevalent drug
against the gram negative bacteria (E. coli, Klebsiella and Enterobacter) has developed
resistance too.

 E.coli followed by Pseudomonas and Klebsiella were found to be the most predeominant
community acquired MDR pathogen.
Increasing incidence of multidrug resistance organisms raises serious concerns and this mandates
strict antibiotic policy to prevent emergence and spread of antibiotic resistance. The rise in
antibiotic resistance emphasizes the importance of sound hospital infection control, rational
prescribing policies, and the need for awareness to use antimicrobial drugs.
It may be concluded from the study that early diagnosis and appropriate treatment of all the
infections and prophylaxis should be based on the current knowledge of bacterial profile and
antibiotic resistance pattern, which should be provided by microbiology laboratory from time to
time.
Limitations of the study
 The major limitation of the study is the duration of the study. The study duration was
short (six months) to collect sufficient data.
 Antibiotic disc sensitivity test results may vary with hospital setting, while infection rate
in a hospital may depends on the hospital environment, antibiotic use and other infection
control practices.
 All these would limit the applicability of the findings of this study to other hospital
settings.
Recommendations
The need of the hour is to promote the judicious use of antibiotics, and steps should be taken at
all levels to minimize the impact and spread of resistance.
Rational use of antibiotics and frequent surveillance are needed to curb this threat and
preserve the antibiotics for the future.
Guidelines are to be strictly made and establish for the judicious and effective use of
antibiotics not only in the health institutions but also everywhere associated with the
antibiotics.

Framing and establishing of antibiotic stewardship plans for all the tiers of healthcare
settings (primary health centres, secondary and tertiary hospitals) to monitor and ensure
proper use of antimicrobials.
Promoting and supporting the future research on the drivers of antimicrobial resistance
to control it effectively.
Increase proper immunization coverage that may reduce the use of antibiotics as it plays
a important role in public good.
Implementing rules and regulations for the use of antimicrobial agents in food animals.
Creating awareness on rational use of drugs by educating the community and physicians
to avoid irrational prescribing of antibiotics.
Establishing strict vigilance and control over sale of antimicrobial agents.
Prescription audit has to performed strictly bring down the over the counter (OTC) sale
of antibiotics.
To control hospital and community acquired infections.
To decrease the unnecessary healthcare costs by encouraging the appropriate selection of
antibiotics.

APPENDIX
APPENDIX
APPENDIX - 1 Data collection form
vii
APPENDIX
viii
APPENDIX
APPENDIX 2 Institutional Ethics Committee approval letter
ix
APPENDIX
x
References
REFERENCES
1. World Health Organisation. Antimicrobial resistance. https://www.who.int/health-

topics/antimicrobial-resistance Accessed on June29, 2020.
2. Rattanaumpawan P, Choorat C, Takonkitsakul K, Tangkoskul T, Seenama C, Thamlikitku V.
A prospective surveillance study for multidrug-resistant bacteria colonization in hospitalized
patients at a Thai University Hospital. Antimicrobial Resistance and Infection Control 2018;
7:102. https://doi.org/10.1186/s13756-018-0393-2
3. Madigan MT, Martinko JM, Brock TD. Brock Biology of Microorganisms. 11 ed., Pearson
Prentice Hall; 2006.
4. Strebhardt K, Ullrich A. Paul Ehrlich's magic bullet concept: 100 years of progress. Nature
Reviews: Cancer 2008; 8(6):473-480.
5. Fleming A. On the antibacterial action of culutres of a penicillium, with special reference to
their use in the isolation of B. influenzae. The British Journal of Experimental Pathology
1929;10:226-236.
6. Kresge N, Simoni RD, Hill RL. Selman Waksman: The Father of Antibiotics. The Journal of
Biological Chemistry 2004;279(48):1-3.
7. Wright GD. The antibiotic resistome: the nexus of chemical and genetic diversity. Nature
Publishing Group 2007;5(3):175-186.
8. Tripathi KD. Essentials of Medical Pharmacology. 7th Edition: Jaypee Brothers Medical
Publishers(P) Ltd., New Delhi; 2013. p704-764.
9. Centers for Disease Control and Prevention, Antibiotic Resistance threats in the United States,
2019. Available at: www.cdc.gov/DrugResistance/Biggest-Threats.html. Accessed June 20,
2020.
10. Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, Nisar MA, Alvi RF,
Aslam MA, Qamar MU, Salamat MKF, Baloch Z. Antibiotic resistance: a rundown of global
crisis: infection and drug resistance. Dove press journal June 2018;11:1645-1658.
doi -https://doi.org/10.2147/IDR.S173867
11. Jin DJ, Gross CA. Mapping and sequencing of mutations in the Escherichia coli rpoB gene
that lead to rifampicin resistance. Journal of molecular biology 1988;202(1):45-58.
12. Goldstein BP. Resistance to rifampicin:a review. The Journal of antibiotics. 2014;67(9):625-
30.
13. Taniguchi H, Aramaki H, Nikaido Y, Mizuguchi Y, Nakamura M, Koga T, et al. Rifampicin
REFERENCES
resistance and mutation of the rpoB gene in Mycobacterium tuberculosis. FEMS

microbiology letters 1996;144(1):103-8.
14. Redgrave LS, Sutton SB, Webber MA, Piddock LJ. Fluoroquinolone resistance: mechanisms,
impact on bacteria, and role in evolutionary success. Trends Microbiol 2014;22(8):438-45.
15. Katayama Y, Ito T, Hiramatsu K. A new class of genetic element, staphylococcus cassette
chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrobial
agents and chemotherapy 2000;44(6):1549-55.
16. Hartman BJ, Tomasz A. Low-affinity penicillin-binding protein associated with betalactam
resistance in Staphylococcus aureus. Journal of bacteriology 1984;158(2):513-6.
17. Poole K. Efflux-mediated antimicrobial resistance. The Journal of antimicrobial
chemotherapy 2005;56(1):20-51
18. Borges-Walmsley MI, McKeegan KS, Walmsley AR. Structure and function of efflux pumps
that confer resistance to drugs. The Biochemical journal 2003;376(Pt 2):313-38. 130
19. McMurry L, Petrucci RE, Jr., Levy SB. Active efflux of tetracycline encoded by four
genetically different tetracycline resistance determinants in Escherichia coli. Proceedings of
the National Academy of Sciences of the United States of America 1980;77(7):3974-7.
20. Butaye P, Cloeckaert A, Schwarz S. Mobile genes coding for efflux-mediated antimicrobial
resistance in Gram-positive and Gram-negative bacteria. Int J Antimicrob Agents
2003;22(3):205-10.
21. Bissonnette L, Champetier S, Buisson JP, Roy PH. Characterization of the non enzymatic
chloramphenicol resistance (cmlA) gene of the In4 integron of Tn1696: similarity of the
product to transmembrane transport proteins. Journal of bacteriology 1991;173(14):
4493-502.
22. Baucheron S, Tyler S, Boyd D, Mulvey MR, Chaslus-Dancla E, Cloeckaert A. AcrAB-TolC
directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium
DT104. Antimicrobial agents and chemotherapy 2004;48(10):3729-35.
23. Pai H, Kim J, Kim J, Lee JH, Choe KW, Gotoh N. Carbapenem resistance mechanisms in
Pseudomonas aeruginosa clinical isolates. Antimicrobial agents and chemotherapy
2001;45(2):480-4.

REFERENCES
24. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant

Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. The Journal of
antimicrobial chemotherapy 1997;40(1):135-6.
25. Shaw WV, Brodsky RF. Characterization of chloramphenicol acetyltransferase from
chloramphenicol-resistant Staphylococcus aureus. Journal of bacteriology 1968;95(1):28-36.
26. Shaw WV. Enzymatic chlorampheicol acetylation and R factor induced antibiotic resistance
in Enterobacteriaceae. Antimicrob Agents Chemother (Bethesda) 1966;6:221-6.
27. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug resistance updates :
reviews and commentaries in antimicrobial and anticancer chemotherapy 2010;13(6):151-
71.
28. CHAIN EPAE. An Enzyme from Bacteria able to Destroy Penicillin. Nature 1940:1.
29. High levels of antibiotic resistance found worldwide, new data shows
https://www.who.int/mediacentre/news/releases/2018/antibiotic-resistance-found/en/.
Access date: 12/6/2020
30. Morris AK, Masterton RG. Antibiotic resistance surveillance: action for international studies:
Journal of antimicrobial chemotherapy (JAC) 2002;49:7-10.
31.Turner PJ. MYSTIC (Meropenem Yearly Susceptibility Test Information Collection): a
global review. J antimicrob chemother 2000;46 suppl T2:9-23.
https://pubmed.ncbi.nlm.nih.gov/11065145/
32. Roca I, Akova M, Baquero F, Carlet J, et al. The global threat of antimicrobial resistance:
science for intervention. New microbes and new infections July 2015;6:22-29.
doi- http://dx.doi.org/10.1016/j.nmni.2015.09.004
33. Knobler SL, Lemon SM, Najafi M, et al., editors.The Resistance Phenomenon in Microbes
and Infectious Disease Vectors: Implications for Human Health and Strategies for
Containment: Workshop Summary. Washington (DC), National Academies Press (US); 2003.
34. World Health Organization. Antibiotic resistance. Available at: https://www.who.int/news-
room/fact-sheets/detail/antibiotic-resistance. Accessed on: 16/7/2020
35. Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted
phenomenon. Pathogens and global health 2015;109:309-316.
doi- 10.1179/2047773215Y.0000000030
36. Ventola C L. The antibiotic resistance crisis part1: causes and threats. P&T April 2015; vol.
REFERENCES
40 No. 4: 277-283.
37. Gandra S, Joshi J, Trett A, Lamkang AS and Laxminarayan R. Scoping report on
antimicrobial resistance in India. Centre for Disease Dynamics, Economics and Policy nov
2017; Pg2-10.
38. Antibiotic resistance: the silent pandemic.
http://www.pmlive.com/pmhub/market_access/porterhouse_medical/press_releases/
antibiotic_resistance_the_silent_pandemic?SQ_DESIGN_NAME=2. Access date: 16/6/2020
39. Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario.
Indian journal of medical research 2019 Feb;149(2):119–128.
doi: 10.4103/ijmr.IJMR_331_18
40. Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade
since emergence of New Delhi metallo-β-lactamase in India. Indian J Community Med
2019;44:4-8
41. Ranjalkar J, Chandy SJ. India's National Action Plan for antimicrobial resistance – An
overview of the context, status, and way ahead. J Family Med Prim Care 2019;8:1828-34.
42. Van Boeckel TP, et al. Global antibiotic consumption 2000 to 2010: an analysis of national
pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–50. doi:10.1016/S1473-
3099(14)70780-7 PMID: 25022435.
43. Laxminarayan et al. Achieving global targets for antimicrobial resistance. Science 2016;
353(6302):874-875.
44. Centers for Disease Control and Prevention, Office of Infectious Disease. Antibiotic
resistance threats in the United States 2013. Available at:
https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
Accessed on June 15, 2020.
45. The antibiotic alarm. Nature 2013;495(7440):141.
46. Read AF, Woods RJ. Antibiotic resistance management. Evol Med Public Health
2014;2014(1):147.
47. Asensio et al. Trends in yearly prevalence of third-generation cephalosporin and
fluoroquinolone resistant Enterobacteriaceae infections and antimicrobial use in Spanish
hospitals, Spain, 1999 to 2010. EuroSurveillance 2011;16(40):19983.
48. Taneja, Neelam. Changing epidemiology of shigellosis and emergence of Ciprofloxacin
REFERENCES
resistant Shigellae in India. Journal of Clinical Microbiology 2007;45(2):678-679.

49. Kotwani, et al. Antimicrobial drug prescribing patterns for community-acquired
pneumonia in hospitalized patients: A retrospective pilot study from New Delhi,India. Indian
Journal of Pharmacology 2015;47(4);375.
50. Kotwani, Anita,et al. Access to antibiotics in New Delhi, India: Implications for antibiotic
policy. Journal of Pharmaceutical Policy and Practice 2013;6(1):6.
51. Gandra, Sumanth, et al. Trends in antibiotic resistance among major bacterial pathogens
isolated from blood cultures tested at a large private laboratory network in India, 2008–
2014. International Journal of Infectious Diseases 2016;50:75-82.
52. Gautam,et al . Fixed dose drug combinations (FDCs): Rational or irrational: A view point.
British Journal of Clinical Pharmacology 2008;65(5):795-796.
53. Shankar, et al. Responsible use of fixed-dose combination antibiotics in
India. The Lancet Global Health 2016;4(10): e689.
54. Keche, Yogendra, et al. Self medication pattern in rural areas in Pune, India. International
Journal of Medicine and Public Health 2012;2(4):7-11.
55. Nair, Abhilasha, et al. Pattern of selfmedication with antibiotics among undergraduate
medical students of a government medical college. International Journal 2015;1(3): 9.
56. Chandy, et al. Antibiotic use and resistance: Perceptions and ethical challenges
among doctors, pharmacists and the public in Vellore, South India. Indian Journal of
Medical Ethics 2013;10(1):20-27.
57. Kotwani, et al. Factors influencing primary care physicians to prescribe antibiotics
in Delhi India. Family Practice 2010;27(6):684-690.
58. Swapna, et al . Incidence of antibiotic residues in farmed shrimps from the southern states
of India. Indian Journal of Geo-Marine Sciences 2012;41(4):344-347.
59. Liu, et al. Emergence of plasmid mediated colistin resistance mechanism MCR-1
in animals and human beings in China: A microbiological and molecular biological study.
The Lancet Infectious Diseases 2016;16(2):161-168.
60. Marathe, Nachiket P., et al. Untreated urban waste contaminates Indian river sediments
with resistance genes to last resort antibiotics.Water Research 2017;124:388-397.
61. Ramasubramanian, et al. Epidemiology of healthcare acquired infection: An Indian
perspective on surgical site infection and catheter related blood stream infection. Indian
REFERENCES
Journal of Basic and Applied Medical Research 2014;3:46-63.

62. Treatment Guidelines for Antimicrobial Use in Common Syndromes; 2019.
63. Sartelli M, Kluger Y, Ansaloni L, et al. A Global Declaration on Appropriate Use of
Antimicrobial Agents across the Surgical Pathway. Surgical infections 2017;18:846-853.
64. Richardson LA. Understanding and overcoming antibiotic resistance. PLoS Biol 2017 Aug;
15(8): e2003775. doi: 10.1371/journal.pbio.2003775
65. Reta A, Kifilie AB, Mengist A. Bacterial Infections and their Antibiotic Resistance Pattern in
Ethiopia: A Systematic Review. Hindawi, Advances in Preventive Medicine 2019; 4380309.
https://doi.org/10.1155/2019/4380309
66. Moremi N, Claus H et al. Antimicrobial resistance pattern: a report of microbiological
cultures at a tertiary hospital in Tanzania. BMC Infectious Diseases 2016;16:756. DOI
10.1186/s12879-016-2082-1.
67. Parihar RS., Dallaram et al. Bacteriological Profile and Antimicrobial Susceptibility
Patterns of Blood Borne Pathogens in a Tertiary Care Center, Jodhpur (Rajasthan), India.
Int.J.Curr.Microbiol.App.Sci. 2018;7(10):1785-1792.
68. Nazneen S, Mukta K et al. Bacteriological trends and antibiotic susceptibility patterns of
clinical isolates at Government Cancer Hospital, Marathwada. Indian J Cancer 2016;53:583-
6.
69. Paul R, Ray J et al. Antibiotic resistance pattern of bacteria isolated from various clinical
specimens: an eastern Indian study. Int J Community Med Public Health 2017;4:1367-71.
70. Bhardwaj N, Khurana S et al. Pattern of antimicrobial resistance of Gram-negative bacilli in
surgical site infections in in-patients and out-patients at an Apex Trauma Center: 2013–2016.
J Lab Physicians 2018;10:432-6.
71. Vadwai V, Nerurkar V et al. Antimicrobial Resistance Pattern among Community-Acquired
Gram-Positive and Gram-Negative Bacterial Bloodstream Isolates in India. Annals of
Clinical and Laboratory Research 2015;ISSN 2386-5180;3(2):10.
72. Orlando V, Monetti VM et al. Drug Utilization Pattern of Antibiotics: The Role of Age, Sex
and Municipalities in Determining Variation. Risk Management and Healthcare Policy,Dove
Press journal 2020;13.
73. Worku F, Tewahido D. Retrospective Assessment of Antibiotics Prescribing at Public
Primary Healthcare Facilities in Addis Ababa, Ethiopia. Interdisciplinary Perspectives on
REFERENCES
Infectious Diseases 2018;vol.2018:9. https://doi.org/10.1155/2018/4323769

74. Dzelamonyuy E Chem, Anong DN et al. Prescribing patterns and associated factors of
antibiotic prescription in primary health care facilities of Kumbo East and Kumbo West
Health Districts, North West Cameroon. PLoS One 2018;13(3):e0193353.
doi: 10.1371/journal.pone.0193353
75. Yimenu DK, Emam A et al. Assessment of Antibiotic Prescribing Patterns at Outpatient
Pharmacy Using World Health Organization Prescribing Indicators. J Prim Care Community
Health 2019;10:2150132719886942. doi: 10.1177/2150132719886942.
76. Basak S, Singh P et al. Multidrug Resistant and Extensively Drug Resistant Bacteria: A
Study. Journal of Pathogens 2015;vol2016. https://doi.org/10.1155/2016/4065603
77. Batarseh A, Soneah S et al. Antibiotic resistance patterns of multidrug resistant and
extended-spectrum β-lactamase producing Eshcherichia coli urinary isolates at Queen Rania
Al-abdullah Hospital for children,Jordan. Z.U.M.J. Sep 2013;19:289-293.
78. Imran Khan M, Surui Xu et al. Assessment of multidrug resistance in bacterial isolates from
urinary tract-infected patients. Journal of Radiation Research and Applied Sciences
2020;13:1,267-275. doi: 10.1080/16878507.2020.1730579
79. Moini AS, Soltani B et al. Multidrug resistant Escherichia coli and Klebsiella pneumoniae
isolated from patients in Kashan, Iran. Jundishapur J Microbiol.2015 October; 8(10): e27517.
doi: 10.5812/jjm.27517
80. Awasthi TK, Pant ND et al. Prevalence of Multidrug Resistant Bacteria in Causing
Community Acquired Urinary Tract Infection Among the Patients Attending Outpatient.
Department of Seti Zonal Hospital, Dhangadi, Nepal. Nepal Journal of Biotechnology Dec
2015; 3(1):55-59.
81.Organization WH. Global action plan on antimicrobial resistance. Available from:
https://www.who.int/antimicrobial-resistance/global-action-plan/en/. Accessed on: 16/7/2020
82. Organization WH. Global antimicrobial resistance surveillance system ( GLASS) report:
early implementation 2017-2018.
Availablefrom: http://wwwwhoint/drugresistance/surveillance/GLASSmeeting/en/.
Accessed on: 16/7/2020
83. Isah AO, Laing R et al. The Development of Reference Values for the WHO Health Facility
Core Prescribing Indicators. West African Journal of Pharmacology and Drug Research
REFERENCES
2001;18. DOI: 10.4314/wajpdr.v18i1.14718

84. Ramanath K V, Biswas P, Sunny R, et al. Study the antibiotic resistance pattern in a tertiary
care teaching hospital. IJPSR 2019; Vol. 10(2): 819-829.
85. Cardoso T, Almeida M , Friedman N D, et al. Classification of healthcare-associated
infection: a systematic review 10 years after the first proposal. BMC Med. 2014;12:
40. doi: 10.1186/1741-7015-12-40

Co-curricular
Activities
CO-CURRICULAR ACTIVITIES
ALLE POOJITHA ( 170115882011 )

WEBINARS, CONFERENCES and QUIZZES
 Awarded with certificate of excellence for securing 5th place at national level in Mybo
Talent Hunt 2020: Online Pharma game show conducted by Mybo group in July 2020.
 Presented a e-poster in a National level e-poster competition on “Covid -19 Pandemic”

jointly organized by Dr. D.Y. Patil Institute of Pharmaceutical Sciences and The
Association of Pharmaceutical Teachers of India (APTI) in May 2020.
 Participated in the International webinar series lecture-II “Pharmacy Profession In India:

Present Status & Future Challenges” JSSAHER, Mysuru and organized by the
Department of Pharmaceutical sciences, in collaboration with UGC-HRDC, University of
Kashmir, on 14th July, 2020.
 Participated in six day e-Faculty and Student Development Program (e-FSDP) on

“Recent Updates in Pharmacy Practice” held from 25th to 30th June 2020 organized by G.
Pulla Reddy College of Pharmacy, Hyderabad.
WORKSHOPS and COURSES
 Participated in National online workshop on “Generating the Highest Level of Evidence

through Systematic Review and Meta-analysis: Best Alternative for Hospital Based
Projects during the Current Pandemic Situation” held on 28 th & 29th August 2020,
organised by National Institute of Pharmaceutical Education and Research (NIPER),
Guwahati.
 Completed an online course on ‘Covid – 19 Contact Tracing’ authorized by Johns

Hopkins University offered by Coursera.
 Received a certification of completion for GOOD CLINICAL PRACTICE course from

NIDA Clinical Trials Network on 30th April 2020.
 Completed a course on ‘Introduction to Pharmacovigilance’ offered by Uppsala

Monitoring Center (WHO).
 Completed an online course offered by WHO and received a record of achievement on

“Emerging Respiratory Viruses, Including Covid- 19: Methods for Detection, Prevention,
Response And Control” on 5th May 2020.
 Completed an online course on “Standard precautions: Hand hygiene” offered by WHO.
 Received certification for e-module on ‘NSAIDs safety with preclampsia’ from Centre
for Health Education , Awareness Resources and Services on 4 th May 2020.
 Completed an online course on career development program titled “TCS iON career edge
– Knock the lockdown” organised by Tata consultancy services on 14 th June 2020.



V.BINDU MADHAVI (170115882010)

 Participated in Mybo Webinar- 2 on “Writing a Pharm D Thesis” organized by MYBO

Group on 24th May 2020.
 Participated in two day webinar on “Present Day Drift in Pharmacy Practice” held on 6 th
and 7th July 2020 organized by CMR College of Pharmacy, Hyderabad.
 Participated in six day e-Faculty and Student Development Program (e-FSDP) on
“Recent Updates in Pharmacy Practice” held from 25th to 30th June 2020 organized by G.
Pulla Reddy College of Pharmacy, Hyderabad.
 Participated in one day webinar on “International Webinar on Challenges and
Opportunities for Developing Safe and Effective Natural Products” held on 27 th May
2020 organized by MNR College of Pharmacy, Hyderabad.
 Participated in webinar on “Dissecting Pharm. D Internship during COVID-19
Pandemic” Held on 30th May 2020 organized by JSS Academy of Higher Education &
Research, Mysuru.
 Participated in “ International Clinical Trails Day-2020” Held on 20 th May, 2020 by
Clinosol
 Participated in Quiz series organised by Sultan-Ul-Uloom College Of Pharmacy on 5 th
May 2020.
WORKSHOPS
 Completion of the six-hour required course on GOOD CLINICAL PRACTICE organized

by NIDA Clinical Trials Network.
 Participated in national online workshop on “Generating the Highest Level of Evidence
Through Systematic Review and Meta-analysis: Best Alternative for Hospital Based
Projects During the Current Pandemic Situation” held on 28th&29th August 2020
organised by National Institute of Pharmaceutical Education and Research (NIPER),
Guwahati.
 Completed World Health Organisation (WHO) training on COVID-19: Operational
Planning Guidelines and COVID-19 Partners Platform to support Country Preparedness
and Response.
 Completed an online course on “Infection Prevention Control (IPC) For Novel
Coronavirus (COVID-19)” organised by WHO on May 7 2020.
 Completed an online course on “ Signal Detection and Causality Assessment” organised
by Upsala Monitoring Center on March 27,2020.



N. HANISHA GUPTA (170115882004)

 Participated in national webinar on “holistic approaches to optimize treatment outcomes

in severe asthma patients: 9-P’s of severe asthma” organized by KL college of pharmacy,
KLEF (deemed to be university) Guntur district, Andhra Pradesh, in association with
MYBO group on 5th September 2020
 Participated in the International webinar series lecture- II “Pharmacy Profession in India:
Present Status & Future Challenges” delivered by Prof. B. Suresh, President, Pharmacy
Council of India, Pro- Chancellor, JSSAHER, Mysuru and organized by the Department
of Pharmaceutical sciences, in collaboration with UGC-HRDC, University of Kashmir,
on July 14th,2020
 Attended the six-day e-Faculty and Student Development Program (eFSDP) on the
Theme “Recent Updates in Pharmacy Practice” from 25th to 30th June 2020 organized
by Department of pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad in
association with Indian Pharmaceutical Association (IPA)- TS Branch.
 Participated in a three-day national webinar conducted between 13th & 15th June 2020
by SNS College of Pharmacy and Health Sciences, Saravanampatty, Coimbatore-35
 Participated in Mybo Webinar- 2 on “Writing a Pharm D Thesis” organized by MYBO
Group on 24th May 2020
 Participated in “The Covid-19 Awareness Quiz” conducted by MNR College of
Pharmacy on 7th May 2020
 Participated as a delegate in one day conference of “Clinicon” organized by Centre for
Pharmaceutical sciences, Institute of Science & Technology, JNTUH, Kukatpally,
Hyderabad in collaboration with Pharmacon Society for Pharmacy Practice &Clinosol
Research Pvt Ltd on 17th August 2019
WORKSHOPS
 Completed an online course on “COVID-19: Operational Planning Guidelines and

COVID-19 Partners Platform to support country preparedness and response” organised
by WHO on 30thApril
 Completed a six-hour online course on “Good Clinical Practice” organized by NIDA
Clinical Trials Network on 30th April,2020
 Completed an online course “Career Edge - Knockdown the Lockdown” of 10 days
course duration 27th April to 7th May offered by TCS iON
 Completed the online “Computer Aided Drug Design training program” from MARS
Training Academy for a duration of one month i.e. 3rd April 2020- 2nd May 2020
 Completed an online course on “Infection Prevention Control (IPC) for Novel
Coronavirus (COVID-19)” organised by WHO on 30th April 2020

CO-CURRICULAR
CURRICULAR ACTIVITIES


QAMARUNNISA BEGUM SIDDIQUI (170115882028)

 Attended national webinar on “Clinical pharmacy services and role of Pharma D

students” organised by MYBO GROUP on 19th July 2020.
 Attended six-day e-Faculty and student development program on “Recent Updates in

Pharmacy Practice” from 25th to 30th June 2020 organised by Depatment of Pharmacy
Practice, G. Pulla Reddy College of Pharmacy, Hyderabad.
 Participated in Quiz series organised by Sultan-Ul-Uloom College of Pharmacy on 5 th

May 2020.
 Participated in Quiz series organised by Malla Reddy College of Pharmacy.
WORKSHOPS
 Attended National Online Workshop on “Generating the Highest Level of Evidence

through Systematic Review and Meta Analysis: Best Alternative for Hospital Based
Projects During the current pandemic situation”organsied by the departement of
pharmacy practice, National Institute of Pharmaceutical Education and
Research(NIPER),Guwahati on 28th and 29th August 2020.
 Completed World Health Organisation (WHO) training on Infection Prevention and

Control(IPC) for Novel Corona virus (COVID-19) on 4th May 2020.
 Completed six hour online course on Good Clinical Practice on 30 th April 2020.

CO-CURRICULAR
CURRICULAR ACTIVITIES

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A RETROSPECTIVE STUDY ON BACTERIAL INFECTIONS,

ANTIMICROBIAL RESISTANCE PATTERNS AND

SUBMITTED TO THE OSMANIA UNIVERSITY, HYDERABAD

UNDER THE GUIDANCE OF

G. PULLA REDDY COLLEGE OF PHARMACY

QAMARUNNISA BEGUM SIDDIQUI

Prof. Dr. B. Madhava Reddy

Mrs. Gouhar Sultana,

CONTENTS Page no.

Table TITLE Page

Figure Title Page

Antimicrobials - including antibiotics, antivirals, antifungals and antiparasitics - are medicines

1.2 THE DISCOVERY OF ANTIMICROBIAL DRUGS:

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 1

A second revolution in antimicrobial treatment started with the discovery of penicillin by

1.3 CLASSIFICATION OF ANTIBIOTICS: 8

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 2

Figure 1: Bacterial structure and mechanism of action of antibacterial drugs.

Table 1. Classification Of Antibiotics

DRUG CLASS CLASSIFICATION MECHANISM OF ACTION

1. Acid Resistant Alternative to

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 3

DRUG CLASS CLASSIFICATION MECHANISM OF ACTION

CEPHALOSPORINS 1.First generation drugs : Exert bactericidal activity by

MONOBACTAMS  Aztreonam Interferes with bactericidal cell

CARBAPENEMS  Imipenem, Meropenem, Causes rapid bacterial cell

BETA-LACTAMASE  Clavulanic Acid, The beta-lactamase inhibitors

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 4

DRUG CLASS CLASSIFICATION MECHANISM OF ACTION

GLYCOPEPTIDES  Vancomycin, Teicoplanin. Vancomycin inhibits

AMINOGLYCOSIDES  Streptomycin, Amikacin, Inhibition of protein biosynthesis

 Tetracycline ,Doxycycline Inhibits bacterial protein

GLYCYLCYCLINES  Tigecycline. Binds to the 30S ribosomal

CHLORAMPHENICOL - Termination of polypeptide

LINCOMYCINS  Clindamycin. Binds to the 50S ribosomal

MACROLIDES  Erythromycin, Roxithromycin, Macrolides are inhibitors of

OXAZOLIDINONE  Linezolid Inhibition of bacterial

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 5

DRUG CLASS CLASSIFICATION MECHANISM OF ACTION

FLUOROQUINOLONES 1. First generation drugs : Inhibition of topoisomerase

NITRO IMIDAZOLES  Metronidazole, Tinidazole, It diffuses into the organism,

RIFAMYCINS  Rifamycin, rifampin, rifabutin, Rifamycins bind to and inhibit

SULFONAMIDES 1.Short acting (4-8 hr) : They are competitive inhibitor of

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 6

DRUG CLASS CLASSIFICATION MECHANISM OF ACTION

NITROFURAN  Nitrofurantoin It is activated inside bacteria

POLYPEPTIDES  Polymyxin B, Colistin, Polymyxin and Colistin

Bacitracin inhibits bacterial

1.4 CDC CLASSIFICATION OF ANTIBIOTIC-RESISTANT BACTERIAL

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 7

Table 2. CDC Assessment Of Antibacterial Resistance Threats

URGENT THREATS SERIOUS THREATS CONCERNING THREATS

 Carbapenem -resistant  Drug-resistant  Erythromycin-resistant group

1.5 EMERGENCE OF AMR:

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 8

1.6 MECHANISMS OF RESISTANCE:

1) Modification of the target

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 9

2) Limiting access to the target

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 10

in detail elsewhere.17 Usually efflux is accommodated through molecule specific or multidrug

3) Modification of the antibiotic

Resistance to antibiotic compounds by degradation or modification of the active compound is of

Dept. of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad Page 11