Chemotherapy - General Introduction

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Chemotherapy
Chemotherapy:  Antimicrobial drugs
General Considerations  Treatment of systemic infections with
specific drugs that can selectively suppress
microbial pathogens without significant
toxicity to host.
 Due to analogy between the malignant cell

and the pathogenic microbes, treatment of
neoplastic diseases with drugs is also called
‘chemotherapy’.
PHA 405T, Pharmacology-2
Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal
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History Various terminology

 The history of chemotherapy may be divided  Antimicrobials
into 3 phases
 The period of empirical use  Antibiotics
chaulmoogra oil by the Hindus in leprosy

 chenopodium by Aztecs for intestinal worms
 Semisynthetic antibiotics
 mercury by Paracelsus (16th century) for syphilis
 Antibacterials, antivirals, antifungal
 cinchona bark (17th century) for fevers
 Bacteriostatic
 Ehrlich’s phase of dyes and organometallic  Bactericidal
compounds (1890–1935): dyes that stains,
methylene blue, could kill bacteria  Fungistatic
 The modern era of chemotherapy
 Domagk : 1935 : Prontosil  a sulfa dye  Fungicidal
 Fleming: 1939: Penicillin
 Waksman: 1944: Streptomycin
Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal
3 Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal
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Prokaryotes vs Eukaryotes Classification of antimicrobials

Different ways of classification
Prokaryotic cell Eukaryotic cell
1. Chemical Structure
 Size: 1-10μM  10-100μM
2. Mechanism of action
 Rigid cell wall  Plasma membrane
 Subcellular organs  Present
3. Type of organisms against which it is
absent / indistinct active
 Enzymes at cell 4. Spectrum of activity
 At mitochondria
membrane 5. Type of action
 70S: 30 S and 50S  80s: 60s and 40s 6. Source of the antibiotic
ribosomes
S= Svedberg unit = 10-13 sec “Measure of sedimentation rate
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Classification I: Chemical Structure Classification I: Chemical Structure
1. Sulfonamides  Dapsone, Sulfamethoxazole 11. Oxazolidinone: Linezolid.

2. Diaminopyridines  Trimethoprim, Pyrimethamine 12. Polypeptides Polymyxin, colistin, Bacitracin
3. Quinolones  Nalidixic acid, Ciprofloxacin 13. Nitrofurans Nitrofurantoin, Furazolidone
4. β lactams  Penicillins, cephalosporins, 14. Nitroimidazoles Metronidazole, tinidazole
monobactams 15. Imidazoles  Miconazole, Clotrimazole
5. Tetracycline  Doxycycline 16. Nicotinic acid derivatives: Isoniazid,
6. Nitrobenzene derivative: Chloramphenicol. Pyrazinamide, Ethionamide.
7. AminoglycosidesStreptomycin, gentamicin 17. Polyene antibiotics: Nystatin, Amphotericin-B,
8. Macrolides  Erythromycin, Roxithromycin Hamycin.
9. Lincosamide antibiotics: Lincomycin, Clindamycin. 18. Miscellaneous  Rifampicin, Griseofulvin,
10. Glycopeptide antibiotics: Vancomycin, Ethambutol, Clofazimine
Teicoplanin.
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Class II: Mechanism of Action Class III: Type of Microbe affected

1. Inhibits Cell wall synthesis 1. Antibacterial penicillins,
β lactams, vancomycin, bacitracin, cycloserine
2. Cause Leakage of Cell membranes aminoglycosides
Polymyxins, Colistin, bacitracin, amphotericin, nystatin,
Hamycin 2. Antifungal  Griseofulvin,
3. Inhibits protein synthesis Tetracyclines, Amphotericin
Chloramphenicol,
4. Misreads m-RNA Streptomycin, Gentamicin 3. Antiviral  Idoxuridine, Acyclovir,
5. Inhibits DNA gyrase Quinolones Amantadine
6. Interferes with DNA functionRifampicin,
Metronidazole 4. Antiprotozoal  Chloroquine,
7. Inhibits DNA synthesis  Idoxuridine, Acyclovir, Pyrimethamine
Zidovudine
8. Inhibits intermediary metabolism  sulfonamides, 5. Anthelmentic Mebendezole,
PAS, Trimethoprim, Ethambutol
Pyrantel, DEC
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Class IV: Spectrum of activity Class V: Type of Action

Primarily Bacteriostatic
 Narrow Spectrum Sulfonamides, Tetracycline, Chloramphenicol,
 Penicillin G, Streptomycin, Erythromycin, Ethambutol
Erythromycin
Primarily Bactericidal
Penicillin, Cephalosporins, Aminoglycosides,
Vancomycin, Nalidixic acid, Rifampicin, Isoniazid
 Broad Spectrum Co-trimoxazole
 Tetracycline, Chloramphenicol

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Classifn VI: Source Problems of Chemotherapy

 Fungal
1) Toxicity : a] Local & b] Systemic
 Penicillin, Cephalosporin, Griseofulvin
 Bacteria 2) Hypersensitivity
 Polymyxin, Colistin, Aztreonam
3) Drug Resistance
 Actinomycetes
 Aminoglycosides, Tetracyclines, 4) Superinfection
Choloramphenicol, Macrolides
5) Nutritional deficiency
6) Masking of Infections

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1a. Toxicity : Local 1b. Toxicity: Systemic

 Most AMA have systemic toxicity
Local  Safe (high therapeutic index)
 Local: Irritation  Penicillin, Cephalosporins [some], Erythromycin
 Safe even at 100 times therapeutic dose
 At site of administration
 Gastric irritation, pain  Moderately toxic (lower therapeutic index)
 Pain, abscess at site of i.m.  Aminoglycosides 8th cranial nerve, Nephrotoxicity
 Tetracyclines  Liver & kidney damage
 Thrombophlebitis
 Chloramphenicol  bone marrow depression
 Most antimicrobials are irritant
 Particularly erythromycin, tetracyclines,  Very toxic (very low therapeutic index)
some cephalosporins, chloramphenicol  Polymyxin B  neurological & kidney toxicity
 Vancomycin  hearing loss & Nephrotoxicity
 Amphotericin  kidney, bone marrow, neurological
toxicity
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2. Hypersensitivity 3. Drug Resistance

 Most AMAs cause hypersensitivity  “unresponsiveness of a microorganism to
an AMA”
 unpredictable and unrelated to dose  Natural : Some microbes have always been
resistant to certain AMAs
 Due to lack of metabolic process or the target site
 From rashes to anaphylactic shock affected by AMAs
 gram-negative bacilli are resistant to penicillin-
 Most frequent  penicillins, G
 aerobic organisms resistant to metronidazole
cephalosporins, sulfonamides  anaerobic bacteria resistant to aminoglycoside
antibiotics
 Acquired: It is the development of resistance by an
organism (which was sensitive before) due to the
use of an AMA over a period of time.
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3. Drug Resistance Mechanism of drug resistance

 Acquired resistance:
1. Mutation:
 Occurs on prolonged exposure to the AMA
1. Single step
 Major clinical problem
2. Multistep
 Depends on both AMA & microbe
 Some microbes are more susceptible to resistance Eg

2. Gene transfer:
tubercle bacteria, staphylococci
1. Conjugation
 Some are less prone: Strep pyogenes still sensitive to
2. Transduction and
penicillin
3. Transformation
 Gonococci rapidly developed resistance to
sulfonamides but slowly to penicillin

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A. Mutation: A. Mutation
1. Stable and heritable genetic change 1. Single step:
2. Develops spontaneously and randomly  A single gene mutation may confer high degree of
resistance
3. Any sensitive population of a microbe  emerges rapidly,
contains a few mutant cells, which  e.g. enterococci to streptomycin, E. coli and
require higher concentration of the AMA Staphylococci to rifampin
for inhibition. 2. Multistep:
4. Mutant cells proliferate when the  A number of gene modifications are involved
 sensitivity decreases gradually in a stepwise
sensitive cells are eliminated by the manner.
AMA.  E.g. Resistance to erythromycin, tetracyclines
5. Vertical transfer of resistance and chloramphenicol is developed by many
organisms in this manner.
6. Eg: Use of single anti-tubercular drug

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B. Gene transfer (infectious

resistance) 1. Conjugation
1. An important mode of resistance
 The resistance causing gene is passed from
2. Transfer of DNA (chromosomal or plasmid)
one organism to the other; is called horizontal
carrying resistance gene
transfer of resistance.
3. Occurs through the sex pili during conjugation
4. The gene carrying the ‘resistance’ or ‘R’ factor is
 Rapid spread of resistance
transferred only if another ‘resistance transfer
factor’ (RTF) is also present.
 Multidrug resistance 5. More common among gram –ve
6. Occurs more in colon, rich in microflora
7. Sometimes from nonpathogenic to pathogenic
microbes
 chloramphenicol resistance of typhoid bacilli,
 streptomycin resistance of E. coli,
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Mechanism of gene transfer Gene transfer contd..

2. Transduction
 Gene transfer through a bacteriophage
 R factor enters virus, delivered to infected
bacterium
 Occurs in penicillin, erythromycin,
chloramphenicol
3. Transformation
 R factor from a resistant bacterium enters the
medium
 Picked up by a nonresistant bacterium
 Rare eg pneumococcal resistance to
penicillin G
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Nature/type of Resistant bacteria Cross Resistance

1. Drug tolerant: Loss of affinity of the target  Definition: Resistance to one AMA confers resistance
biomolecule of the microorganism for a to a closely related AMA
particular AMA 1. Total cross resistance
1. Loss of AMA target
 Eg. Sulfonamides & Tetracyclines : resistance to
Eg. Staph aureus, E coli with RNA polymerase that does not bind
rifampicin one means resistance to all
2. Altered metabolic pathway 2. Partial cross resistance
Eg. Sulfonamide resistant bacteria switch to using preformed folic
acid instead of synthesizing it  Eg. Resistance to gentamicin but not amikacin
2. Drug destroying: The resistant microbe consists 3. Two way
an enzyme which inactivates the drug  Eg. erythromycin   Clindamycin two way
 β lactamase produced by Staphylococci, Haemophilus, 4. One way
Gonococci
 Aminoglycosides are acetylated, phosphorylated etc
 Neomycin resistance leads to streptomycin
resistance
3. Drug Impermeable
 Hydrophilic AMAs enter through porins  Not vice versa
 Eg. chloroquine resistant falciparum do not take up drug
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Prevention of Drug resistance 4. Superinfection (Suprainfection)

1. Avoid Indiscriminate use  Appearance of a new infection while treating
2. Avoid inadequate use another
 Intestinal microflora inhibit pathogens
3. For acute localized infections in otherwise
 by a substance called bacteriocin
healthy patients, symptom-determined shorter  Microflora compete with pathogens for nutrition
courses of AMAs are advocated.  Prolonged use of broad spectrum kills microflora 
4. Use fast acting, selective AMA [Narrow superinfection
spectrum]  Killing microflora  normally nonpathogenic
components of microflora  becomes pathogenic
5. Use broad spectrum only when needed
 For eg Candida
6. Combination therapy for long term treatment  AMA: Eg. tetracycline, chloramphenicol >> amoxicillin
7. Treat resistance-prone infections intensively  cause superinfection diarrhoea because of incomplete
absorption, thus higher amounts reach the lower bowel
Eg, Staph aureus, E coli, M tuberculosis, and cause greater suppression of colonic bacteria.

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Superinfection continued Superinfection continued

 More when combinations are used
To minimize superinfections:
 More when host immunity is compromised
 Eg corticosteroids, immunosuppressants, 1. Use specific (narrow-spectrum) AMA whenever
diabetes, AIDS
 Site of superinfections : oropharynx, intestinal, possible.
respiratory, genitourinary tracts 2. Do not use antimicrobials to treat insignificant,
 Superinfections  more difficult to treat
 Common superinfections self-limiting or untreatable (viral) infections.
 Candida albicans  diarrhoea, thrush, 3. Do not unnecessarily prolong antimicrobial
vulvovaginitis
 Staphylococci  enteritis therapy
 Clostridium difficile  pseudomembranous
enterocolitis

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5. Nutritional deficiencies 6. Masking of an infection

 Some of the B complex group of vitamins and  A short course of an AMA may be sufficient to
vit K synthesized by the intestinal flora is
utilized by man. treat one infection but only briefly suppress
another one
 Prolonged use of antimicrobials which alter this  The other infection will be masked initially, only
flora may result in vitamin deficiencies.
 Neomycin causes morphological to manifest later in a severe form.
abnormalities in the intestinal mucosa—  Syphilis masked by the use of a single dose of
steatorrhoea and malabsorption syndrome penicillin which is sufficient to cure gonorrhoea.
can occur.
 Tuberculosis masked by a short course of
streptomycin given for trivial respiratory
infection.
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Choice of an AMA Choice of an AMA

 The choice depends on the particulars of the  Organism-related factors:
1. Clinical diagnosis itself directs choice of the AMA
patient, the infecting organism and the
2. A good guess can be made
drug.
3. Choice to be based on bacteriological Examination
 Patient factors
 Drug factors
1. Age 1. Spectrum of activity
2. Renal and hepatic function 2. Type of activity
3. Local factors 3. Sensitivity of the organism
4. Drug allergy 4. Relative toxicity
5. Pharmacokinetic profile
5. Impaired host defence
6. Route of administration
6. Pregnancy
7. Evidence of clinical efficacy
7. Genetic factors

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Patient-related factor Patient-related factor

1. Age: Affects the kinetics of AMAs
2. Renal and hepatic function:
A. In newborn: chloramphenicol larger doses
produces gray baby syndrome
 Inefficient conjugation and excretion
B. Neonates: Sulfonamides causing kernicterus
 Displacement of bilirubin from binding sites, which
reaches brain through blood brain barrier (which
in not fully developed.)
C. In elderly: Aminoglycoside toxicity
 The t½ of aminoglycosides is prolonged in the
elderly: VIII nerve toxicity
D. Child up to 6years: Tetracycline toxicity
 Discoloration of teeth and bone

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Patient-related factor Patient-related factor

3. Local factors: The conditions prevailing at the site of
infection 5. Anaerobic environment impairs the bacterial
1. Presence of pus and secretions decrease the transport processes
efficacy of most AMAs: especially sulfonamides  Aminoglycosides activity will reduce
and aminoglycosides. 6. Penetration barriers at certain sites may
2. Presence of necrotic material or foreign body hamper the access of the AMA to the site,
including catheters, implants such as in subacute bacterial endocarditis
3. Haematomas foster bacterial growth: (SABE)
Tetracyclines, Penicillins etc. get bound to the
degraded haemoglobin.
4. pH at the site of action:  4. Drug allergy: e.g. drug of choice for syphilis
in a patient allergic to penicillin is tetracycline.
 Lowering of pH at the site of infection
reduces activity of macrolide and
aminoglycoside antibiotics.

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Patient-related factor Organism-related considerations

5. Impaired host defence
 Pyogenic infections occur readily in neutropenic
1. Clinical diagnosis itself directs choice of the
patients. AMA: tuberculosis, amoebiasis
 Bacteriostatic AMA for normal host defence whereas 2. A good guess can be made
cidal drugs for impaired defence  clinical features and local experience
6. Pregnancy 3. Choice to be based on bacteriological
 All AMAs should be avoided. examination:
 Penicillins, many cephalosporins and erythromycin  e.g. bronchopneumonia, meningitis,
are safe osteomyelitis, urinary tract infection, wound
 Tetracyclines and Aminoglycosides are clearly infection, etc. (culture and sensitivity
contraindicated testing)
7. Genetic factors: Primaquine, nitrofurantoin, sulfonamides,
chloramphenicol and fluoroquinolones carry the risk of producing
haemolysis in G-6-PD deficient patient.

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Drug factors Drug factors

1. Spectrum of activity 5. Pharmacokinetic profile
 For definitive therapy: Narrow spectrum AMAs
 ‘concentration-dependent killing’
 For empirical therapy (No information about the
bacteria), often a broad-spectrum drug  Aminoglycosides, FQs etc
2. Type of activity  ‘time-dependent killing’
 several acute infections resolve faster with a cidal  Beta-lactams, glycopeptides, macrolides
than a static drug
 Penetration
 A bactericidal antibiotic is superior to bacteriostatic
drug in treating patients with impaired host defence,  FQs have excellent tissue penetration-attain
life-threatening infections high concentrations in soft tissues
3. Sensitivity of the organism : MIC values  Cefuroxime, ceftriaxone in CSf
4. Relative toxicity  Penicillines and aminoglycosides have poor
 A less toxic antibiotic is preferred, e.g. a β-lactam CSF penetration but effective in meningitis
over an aminoglycoside
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Drug factors Antimicrobial Combinations

 Advantages (Objectives) of combined therapy
 6. Route of administration: 1. Synergism
 Certain AMAs are only effective parenterally 2. Reduce ADR
 Aminoglycoside, vancomycin, penicillin-G 3. Prevent resistance
 Oral antibiotics: For less severe infections 4. Broaden spectrum
 Parenteral: For severe infections
 Disadvantages
 7. Evidence of clinical efficacy  Promote a casual rather than rationale outlook in
 Reliable clinical trial data diagnosis / choice of AMA
 May increase incidence of ADRs

 8. Cost-effectiveness: Less expensive drugs are
 Increase superinfections
to be preferred.
 Emergence of resistant organisms in inadequate doses
 Increased cost
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Advantages of combinations contd.. COMBINED USE OF ANTIMICROBIALS
 A. To achieve synergism  Possible combinations

 If the MIC of each AMA is reduced to 25% or less,  Bacteriostatic + Bactereostatic
 Additive: Tetracycline + Chloramphenicol
the pair is considered synergistic,
 Supra-additive effect (cidal):
 IF MIC is 25–50% of each is considered additive Sulphonamide + Trimethoprim
(Sequential blockade)
and
 More than 50% of MIC of each indicates  Bactericidal + Bactericidal

antagonism.  Penicillin + Aminoglycoside, INH+ Rifampin
(frequently additive and sometime
synergistic)

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COMBINED USE OF ANTIMICROBIALS Advantages of combinations contd..

 Bactericidal + Bacteriostatic B. Reduces ADRs
 (i) If the organism is highly sensitive to the Combinations help reduce dose  ↓ ADRs
cidal drug—response to the combination is
equal to the static drug given alone (apparent
Eg Streptomycin + Penicillin G in bacterial
antagonism) endocarditis
 Penicillin + tetracycline/chloramphenicol on C. Reduces emergence of resistance
pneumococci which are highly sensitive to penicillin.
 Because cidal drugs act primarily on rapidly
INH + Rifampin + Pyrazinamide in
multiplying bacteria, while the static drug retards Tuberculosis
multiplication.
D. Broaden spectrum
 (ii) If the organism has low sensitivity to the
cidal drug—synergism may be seen Useful in severe infections, mixed infections
 Penicillin + sulfonamide for actinomycosis
 Rifampin + dapsone in leprosy.
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Disadvantages Prophylactic use of AMA

 1. They foster a casual rather than rational  Against specific organisms
outlook in the diagnosis of infections and choice  Tuberculosis in high risk children
of AMA.  Malaria in endemic areas
 2. Increased incidence and variety of adverse  Meningiococcal meningitis
effects. Toxicity of one agent may be enhanced  Prevention in high risk situations
by another, e.g. vancomycin + tobramycin and  Surgery
gentamicin + cephalothin produce exaggerated  Dental extraction, endoscopy,
kidney failure.  Catheterisation
 3. Increased chances of superinfections.  Immunocompromised patients
 4. If inadequate doses of nonsynergistic drugs × Prevention of infection in general
are used—emergence of resistance may be × Neonates after instrumental delivery
promoted. × Elective surgery
 5. Higher cost of therapy. × Unconscious patients (for respiratory
infections)
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Failure of AMAs Pathogenic microbes classes

 Bacteria
 1. Improper selection of drug, dose, route or  Higher forms: Actinomycetes, Streptomycetes
duration of treatment.  Lower forms: Cocci, Bacilli, Vibrio, Spirilla
 2. Delay in starting the treatment.  Special: Acid-Fast Bacilli: M. avium, M. tuberculosis, M.
leprae
 3. Failure to take necessary adjuvant  Spirochetes: (no rigid cell wall, slender / spiral shaped)
measures, e.g. drainage of abscesses  Treponema pallidium: Syphilis
 4. Poor host defence—as in leukaemias  Borrelia recurrentis: Body lice, relapsing fever
 5. Accessibility: Barriers, eg. SABE  Rickettsiae:

 Rigid cell wall, G-ve, Rocky Mountain spotted fever,
 6. Trying to treat untreatable (viral) infections typhus fever
 7. Presence of dormant or altered organisms  Chlamydiae:
 Rigid cell wall, G-ve, Possess RNA/DNA (Like bacteria),
Grows only inside other cells (Like virus)
 Miscellaneous: M. pneumonia (atypical pneumonia),
Ureaplasma, Pneumocystis carini (AIDS-Pneumonia)
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Cocci Bacilli
 Gram +  Gram –  Gram +
 Staphylococcus  Neisseria  Clostridium tetani: Tetanus
aureus gonorrhoeae
 Bacteremia,  Gonorrhoea,  C. perfringens: Gas gangrene
septicaemia / Urethritis, Cervitis
abscess
 C. difficle: P. colitis
 Streptococcus  N. meningitidis  C. botulinum: Botulism (Food
pyogens  Meningitis poisoning)
 Pharyngitis, sinusitis,
otitis, rheumatic fever  Corynebacterium diphtheria:
 Strepto. faecalis  Moraxella catarrhalis Diphtheriae
 Endocarditis, UTI  Sinusitis,
 Strepto. pneumoniae pneumonia, otitis  Bacillus anthracis: Anthrax,
 Pneumoniae, pneumoniae
meningitis, sinusitis

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Bacilli
 Gram -ve  Gram –ve: Others (Aerobic)
 H. influenza: Sinusitis,
 Enterobacteriaeceae bronchitis, pneumoniae,
 E. coli: UTI, Dysentry meningitis
 S. typhi: Typhoid,  P. aeruginosa: UTI, HAI,
food poisoning Burns
 Shigella:  Y. pestis: Plague
Gastroenteritis,  Brucella abortus:
Dysentry Brucellosis
 Klebsiella: HAUTI,  V. cholera: Cholera
pneumonia
 Bordetella pertussis:
 H. pylori: Peptic ulcer Whooping cough
 Bacteroids fragilis: Brain

and lung abscess
(Anaerobic) 57 58
Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal
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Chemotherapy - General Introduction

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Chemotherapy - General Introduction

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23/10/2019

 Due to analogy between the malignant cell

PHA 405T, Pharmacology-2

History Various terminology

Prokaryotes vs Eukaryotes Classification of antimicrobials

Classification I: Chemical Structure Classification I: Chemical Structure

1. Sulfonamides  Dapsone, Sulfamethoxazole 11. Oxazolidinone: Linezolid.

Class II: Mechanism of Action Class III: Type of Microbe affected

Class IV: Spectrum of activity Class V: Type of Action

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Classifn VI: Source Problems of Chemotherapy

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

1a. Toxicity : Local 1b. Toxicity: Systemic

2. Hypersensitivity 3. Drug Resistance

3. Drug Resistance Mechanism of drug resistance

 Some microbes are more susceptible to resistance Eg

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

B. Gene transfer (infectious

Mechanism of gene transfer Gene transfer contd..

Nature/type of Resistant bacteria Cross Resistance

Prevention of Drug resistance 4. Superinfection (Suprainfection)

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Superinfection continued Superinfection continued

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

5. Nutritional deficiencies 6. Masking of an infection

Choice of an AMA Choice of an AMA

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Patient-related factor Patient-related factor

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Patient-related factor Patient-related factor

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Patient-related factor Organism-related considerations

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

Drug factors Drug factors

Drug factors Antimicrobial Combinations

 May increase incidence of ADRs

Advantages of combinations contd.. COMBINED USE OF ANTIMICROBIALS

 A. To achieve synergism  Possible combinations

 More than 50% of MIC of each indicates  Bactericidal + Bactericidal

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

COMBINED USE OF ANTIMICROBIALS Advantages of combinations contd..

Disadvantages Prophylactic use of AMA

Failure of AMAs Pathogenic microbes classes

 5. Accessibility: Barriers, eg. SABE  Rickettsiae:

Dept of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal

 Bacteroids fragilis: Brain

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