Penyusunan Antibiogram

dr. Fera Ibrahim,MSc., Ph.D, SpMK(K)

Perdalin

SEMINAR PPRA PERDALIN : 13 – 14 Desember 2022

Antimicrobial resistance (AMR) is now well
recognized as a global health threat

US Centres for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.
http://www.cdc.gov/drugresistance/threat-report-2013/ (accessed 8 April 2015).
 Challenges related to
antimicrobial resistance
• Antimicrobial Resistance (AMR) is an increasingly serious
threat to global public health that requires action across all
government sectors and society1, 3
• Treatment failure, high morbidity and mortality2
o Patients with infections caused by drug-resistant bacteria are at
increased risk of poor clinical outcomes and potential death

• Economic burden on families and societies2

o The cost of health care for patients with resistant infections is higher
due to longer duration of illness, additional tests and use of more
expensive drugs.

(1) Antimicrobial resistance, 2016, WHO [http://www.who.int/mediacentre/factsheets/fs194/en]

(2) Davies J, Origins and Evolution of Antibiotic Resistance, Microbiol Mol Biol Rev. 2010; 74(3): 417–433.
(3) Levy BS, Factors impacting on the problem of antibiotic resistance, J. Antimicrob. Chemother. 2002; 49(1):25-30.
 Strategies Approach
Against AMR in Hospitals
• Optimizing the duration of choice and dose of empiric therapy:
antimicrobial stewardship
• Optimizing antimicrobial prophylaxis for operative procedures
• Developing and implementing an antibiotic policy and standard
treatment guidelines (STG)
• Monitoring and providing feedback regarding antibiotic resistance
• Improving antimicrobial prescribing by educational and administrative
means
Process for the Development of Hospital
Antibiotic Policy
Hospital Associated Surveillance of AMR/AB
Infection consumption

Cumulative Antibiogram Hospital

Antibiotic Policy

Standard Treatment Guidelines

Antimicrobial Stewardship
Antibiogram
 Cumulative Antibiogram (1)

• Analyses/presentation of data regularly, at least annually

• Inclusion of only final, verified result
• Inclusion of only species with at least ≥30 isolates tested
• Inclusion of diagnostic isolates
• Information only on drugs routinely tested
• Inclusion of the first isolate per patient in the period
analyzed, irrespective of the body site from which the
specimen was obtained
 Cumulative Antibiogram (2)
• Calculation of the percentage susceptibility (%S)
• Avoid the presentation of potentially misleading or
confusing data
• Providing confidence intervals and statistical
significance of changes in the percentage of susceptible
isolates
• Utilizing statistical tools to analyze the data
• Undertaking data stratification to encourage optimal
antimicrobial therapy
Cumulative Antibiogram (3)
• Reviewing the cumulative antibiogram data if
clinical failure occurs after empiric therapy and, if
changes, the trend has to be followed
• Ensuring the quality of the cumulative antibiogram
• Comparing the cumulative antibiogram with
national data
The purposes of the antibiogram
• To guide the empiric selection of antimicrobials
• To use as an educational tool for prescribers
• To monitor antibiotic resistance trends in bacteria
common among patient/resident populations and in
the community
How to get good results to
develop qualified antibiogram?
Laboratory
Complexity of a Laboratory System

Reporting Patient/Client Prep

Sample Collection
Personnel Competency
Test Evaluations
•Data & Laboratory
Management
•Safety
•Customer Service
Sample Receipt and
Accessioning

Record Keeping

Sample Transport
Quality Control
Testing
 Clinical Microbiology Laboratories

GARBAGE IN, QUALITY IN,

GARBAGE OUT QUALITY OUT

 Appropriate Reporting
• clinically appropriate
• guided in interpretative statements
• evidence based
• concurrent with literature
Interpreting Results
Contamination

Colonization

Infection
Interpreting results
Contamination
Blood culture:
(Coagulase-negative
• growing organisms that
staphylococci, diptheroids)
are not from the
intended site culture Urine culture:
Mixed bacterial growth, low
viable counts

Sterile sites:
(Coagulase-negative
staphylococci, diptheroids)
 Interpreting results
Colonisation
• growing organisms that are Throat swabs:
unlikely to cause infection Gram-negative bacilli,
• or growing organisms without coagulase-negative
signs of infection staph

Critical Colonisation
Secret from Non-
• The point when the patient’s infected Wound:
immune system is no longer able Gram-negative bacilli
to control the colonising bacteria
 Specimen: Sputum in CAP
Growth of
• Klebsiella pneumoniae
• Pseudomonas aeruginosa Epithelial cells: 2+
• Candida sp. White cells: 1+
K.pneu P.aeru
Mixed growth of Gram-negative
Amox R bacilli
Amox-Clav.acid S K. pneumoniae and P.aeruginosa:
Cefuroxime I
Scanty
Ciprofloxacin S R
Comment:
Ceftriaxone S R
• presence of epithelial cells which
Ceftazidime S S may indicate sample
Tri/Sulpha S contamination with upper airway
flora.
Pip/Tazo S S
Imipenem S S
Meropenem S S
Interpreting Result
Infection

• The presence of multiplying bacteria that

overwhelms the patient’s immune system and
result in bacterial spreading .
• Active signs and symptoms of disease present
Case
Male, 55, Stroke
• T 380C, HR 100/min
• Leucocytes 19.000/dl
• 2 sets blood culture

Result of both cultures:

• Growth of Staphylococcus epidermidis
CLINICAL SIGNIFICANCE OF
Staphylococcus epidermidis
Sets Sets % % Contam % % Pos Pred
positive obtained Significant Indeterm Value

1 1 0 97 3 55
1 2 2 95 3 20
2 2 60 3 37 98
1 3 0 100 0 5
2 3 75 0 25 91
3 3 100 0 0 100

Tokars, JI. Clin Infect Dis , 2004; 39:333

Indications for When Susceptibility
Testing is Necessary
✓Does the organism contribute to an infectious
process?
✓Does the pathogen belong to a species capable of
exhibiting resistance to common antimicrobial
agents?
✓Can susceptibility be reliably predicted from
knowledge of the organism’s identity?
✓Is a well-standardized method available for that
pathogen?
 AST: Important Consideration
• Testing directly with clinical material (e.g., body fluid)
should not be done
• Follow the basic principles outlined in published
guidelines (CLSI, FDA, EUCAST..)
• The number of antibiotics tested should be limited (CLSI
M100 Table 1A & 1B)
• Report only those agents that are appropriate for
therapeutic use (use generic names)
• For MIC testing: report the MIC + (S, I, R)
• For Disk diffusion: report as (S, I, R)
“report it all and let the doctor decide……..”

does not take into account the reality of

“If the microbiologist names it, the

physician feels obliged to treat it”
 Susceptibility Test Results

Usual report:
‘susceptible to this drug’
‘resistant to this drug’

Interpretative Reading:
• Recognizing unusual results
• Recognizing drugs best avoided owing to their risk
of selecting resistance in the particular pathogen
• Using ‘indicator’ drugs

DM.Livermore, TG Winstanley, KP Shannon. J..of Antimicrobial

Chemotherapy (2001) 48, Suppl.S1
Recognizing Unusual Results:
Resistance requiring confirmation
Examples
• S.aureus
Any of: vancomycin, teicoplanin. linezolid
• Streptococcus pneumoniae
Any of: Meropenem, vancomycin, teicoplanin,
linezolid
• Enterobacteriaceae
Meropenem, imipenem
• Neisseria gonorrhoeae
Any third-generation cephalosporin
• Anaerobes in general
metronidazole
Natural Resistance Typical of Common Pathogens
Examples
• Acinetobacter baumannii
Ampicillin, amoxycillin, 1st gen. cephalosporin

• Pseudomonas aeruginosa
Ampicillin, amoxycillin, 1st and 2nd gen.
cephalosporin, cefotaxime, ceftriaxone, nalidic
acid, trimethoprim

• Salmonella spp.
Cefuroxime (active in vitro, not active in vivo)

• Proteus vulgaris
Ampicillin, amoxycillin, cefuroxime, colistin,
nitrofurantoin

• Streptococcus pneumoniae
Trimethoprim, amynoglycoside
Using “indicator” drugs

Examples
• MRSA: resistant to all β-lactams

• ESBL (ceftazidime, cefpodoxime,

cefotaxime, ceftriaxone):
avoid all cephalosporin

• N.gonorrhoeae (nalidixic acid):

indicate reduced susceptibility to
fluoroquinolones
Guide on how to prepare a hospital antibiogram
Excel data entry form - Helpful hints
• -Add or delete antimicrobials
If your laboratory does not test against a certain antimicrobial, delete that column. Add in antimicrobials
that are missing. Also change abbreviations to match what your laboratory uses. You can also reorder the
columns to make entering the data easier.

• -Add or delete patient characteristics

Each patient will need an ID number in case multiple patients have the same name. Columns like
unit/room/bed are only included if you want to conduct further analysis of the data. You can add columns
for any patient characteristic you may find important or remove any that you will not use.

• -Specimen ID
This column represents the number the laboratory uses to identify the specimen. Sometimes this is called
the accession number. Feel free to rename the column to match what your laboratory uses. If your culture
reports lists multiple organisms for one specimen, those organisms will have the same specimen ID.

• -Specimen date
This column indicates the date of the specimen. Some laboratories will report this by the collection date
while others will use the date the culture was positive. Use whichever terminology your laboratory uses.
The antibiogram will be based on one isolate per patient per analysis period. The first diagnostic isolate for
each antibiotic per organism is collected.
 Amikacin (AMK)
Amoxicillin-Clavulanate (AMC)
Patient ID
Ampicillin (AMP)
Ampicillin-Sulbactam (SAM) Birthdate

ID
Aztreonam (ATM) Gender

Patient
Benzylpenicillin (BPC) Unit

Biapenem (BIPM) Room

Cefazolin (CZO) Birthdate Bed

Cefepime (FEP) Specimen ID

Cefoperazone/Sulbactam (CTX) Specimen type

Cefoxitin (FOX) Specimen date

Ceftazidime (CAZ) Gender Body site

Ceftriaxone (CRO) Pathogen ID

Chloramphenicol (CAM)
Origin

Ciprofloxacin (CIP) Unit Isolate number

Clindamycin (CLI) Amikacin (AMK)

Amoxicillin-Clavulanate (AMC)
Colistin (COL)
Ampicillin (AMP)

Daptomycin (DAP) Ampicillin-Sulbactam (SAM)

Doripenem (DOR)
Room Aztreonam (ATM)

Benzylpenicillin (BPC)

Ertapenem (ETP) Biapenem (BIPM)

Cefazolin (CZO)
Erythromycin (ERY) Cefepime (FEP)

Fosfomycin (FOS)
Bed Cefoperazone/Sulbactam (CTX)

Cefoxitin (FOX)

Gentamicin (GEN/HLG) Ceftazidime (CAZ)

Ceftriaxone (CRO)
Imipenem (IMP) Chloramphenicol (CAM)

Ciprofloxacin (CIP)
Levofloxacin (LVF) Specimen ID
Clindamycin (CLI)
Linezolid (LZN) Colistin (COL)

Daptomycin (DAP)
Meropenem (MEM)
Doripenem (DOR)

Methicillin (MET) Specimen type Ertapenem (ETP)

Erythromycin (ERY)
Moxifloxacin (MFX) Fosfomycin (FOS)

Nafcillin (NAF) Gentamicin (GEN/HLG)

Imipenem (IMP)
Nitrofurantoin (NIT) Specimen date Levofloxacin (LVF)

Linezolid (LZN)
Oxacillin (OXA)
Meropenem (MEM)

Ofloxacin (OFL) Methicillin (MET)

Moxifloxacin (MFX)
Penicillin (PEN) Body site Nafcillin (NAF)

Nitrofurantoin (NIT)
Piperacillin-Tazobactam (TZP)
Oxacillin (OXA)
Polymyxin B (POL) Ofloxacin (OFL)

Penicillin (PEN)
Quinopristin/Dalafopristin (QDA)
Piperacillin-Tazobactam (TZP)

Rifampin (RIF)
Pathogen ID Polymyxin B (POL)

Quinopristin/Dalafopristin (QDA)
Sitafloxacin (STFX) Rifampin (RIF)

Streptomycin (STR/HLS) Sitafloxacin (STFX)

Streptomycin (STR/HLS)
Tetracycline (TCY) Origin Tetracycline (TCY)

Ticarcillin-Clavulanate (TIC)
Ticarcillin-Clavulanate (TIC) Tigecycline (TGC)

Tigecycline (TGC) Tobramycin (TOB)

Trimethoprim/Sulfa (SXT)

Tobramycin (TOB) Isolate number Vancomycin (VAN)

Trimethoprim/Sulfa (SXT)
Vancomycin (VAN)
WHOnet 5.5 → 5.6 (20.12.8)
 What is WHONET?
• Free software developed by the WHO Collaborating
Centre for Surveillance of Antimicrobial Resistance for
laboratory-based surveillance of infectious diseases and
antimicrobial resistance

• Principal goal of the software:

• To enhance local use of laboratory data
• To promote national and international collaboration through the
exchange of data
 What is WHONET? …Cont’
• Can be used by individual laboratories or as part of a national and
international surveillance network
• Available in 28 languages
• Used in over 130 countries around the world
• Managing data from over 2300 clinical public health, veterinary, and
food laboratories
Facilitate:
• The understanding of the local epidemiology of microbial populations
• The selection of antimicrobial agents
• The identification of hospital and community outbreaks
• The recognition of quality assurance problems in laboratory testing
Main Components

• Laboratory Configuration

• Data entry and reporting

• Data analysis
WHONET 5.6
 Laboratory Configuration
• permits the customization of the software for use
in a institution

• Antimicrobials tested in the laboratory can be

indicated

• Surveillance program: patient care areas served,

data field, etc

• Microbial alert of unusual or important organisms

and resistance phenotypes
 Data Entry and Clinical Reporting
• Routine entry of susceptibility test results

• Retrieval, correction and printing of clinical records

• During data entry, WHONET can provide immediate

feedback to technicians on important strain
phenotypes
Data Analysis
• Permitting many types of analysis
• Isolate line listing and summaries
• Antimicrobial susceptibility test statistics
• Zone diameters and MIC histograms
• Antibiotic scatter plots
• Antibiotic resistance profile line-listing and
summaries

• Number of alert features which permit the detection of

unlikely or important results as well as possible hospital
or community outbreaks of bacterial or non-bacterial
species
 BackLink
• Many laboratories already have computer systems for
managing microbiological data:
• Simple desktop software: Microsoft excel,
Access
• Laboratory test instrument: Vitex, Microscan
• Commercial or in-house laboratory
information systems
 BackLink Software
• Facilitate the conversion of data from the computer
system into WHONET (weekly, monthly)

• Avoid manual entry of results into WHONET

• Available free of charge from the WHO as part of the

WHONET package
The antibiogram Report
• Includes the percentage (%) of bacterial isolates
susceptible to each antimicrobial agent tested and
are often reported by :
• Inpatient or outpatient status,
• Individual wards such as intensive care unit, medical
surgical unit, or long term care facility.
• It is usually divided by types of organisms including
Gram-negative bacteria, anaerobes, and Gram-positive
bacteria.
• Specimen types
 trimethoprim/sulfamethoxazole
Number of isolates (2011)

amoxycillin / clavulanate

piperacillin/tazobactam
ampicillin/sulbactam
GRAM NEGATIVE

ciprofloxacin

meropenem
minocycline
ceftazidime
ceftriaxone

gentamicin
ertapenem
aztreonam
cephalexin

tigecycline
imipenem
cefepime
amikacin
Gram-negative
Acinetobacter baumannii 225 45 34 21 25 21 40 22 23 34 37 susceptibility > 80%
Enterobacter spp. 200 97 51 82 51 51 71 80 74 97 100 61 68
Escherichia coli 2050 98 75 75 37 74 74 74 57 99 83 100 100 95 97 58 susceptibility 50-79%
Klebsiella spp. 1050 96 68 69 60 71 70 69 69 92 79 100 99 77 93 61
Pseudomonas aeruginosa 750 93 76 88 86 85 86 91 91 92 susceptibility < 50%
Proteus spp. 280 94 85 86 71 87 87 87 63 99 70 95 100 99 50
not applicable

trimethoprim/sulfamethoxazole
Number of isolates (2011)

GRAM POSITIVE erythromycin

ciprofloxacin

moxifloxacin
clindamycin

vancomycin
daptomycin

tetracycline
fusidic acid
cloxacillin
ampicillin

penicillin
linezolid

Staphylococcus aureus 1700 70 88 70 100 71 19 72 87 100

Staphylococcus aureus (MRSA) 500 0 69 20 100 16 0 53 70 100
Staphylococcus aureus (MSSA) 1200 100 95 90 100 93 27 79 94 100
Enterococcus faecalis 50 100 55 100 57 83 100
Enterococcus faecium 65 3 3 100 3 3 38
Streptococcus pneumoniae 45 100 55 100 96 100 41 49 100
Limitations of making Antibiograms

• Patient population is not homogeneous

• Quality of specimen handling
• Analytical phase of microbiological examination:
• Culture and identification procedures
• Antimicrobial susceptibility test procedures and reporting
• Small number of isolates
Surveillance of Indonesian Network for
Antimicrobial Resistance (SINAR)

Surveilans ini dilakukan oleh Perhimpunan

Dokter Spesialis Mikrobiologi Klinik Indonesia
(PAMKI)

Surveilans ini merupakan lanjutan kegiatan

serupa tahun 2021 di 26 rumah sakit, ( Buku
Surveilans Resistansi Antibiotik Rumah Sakit
Kelas A dan B di Indonesia Tahun 2020)

Buku surveilans resistansi antibiotik pada 51

rumah sakit kelas A, B dan C yang tersebar di
Indonesia, di 15 provinsi yang terdiri dari 16 RS
Kelas A, 30 RS Kelas B dan 5 RS Kelas C. Data ini
diharapkan dapat memperkaya data AMR
nasional dan dapat menjadi acuan penyusunan
antibiogram di rumah sakit yang sesuai dengan
standar internasional.
 Surveillance Purposes
• Assist clinicians in choosing antibiotics as empiric
therapy if the hospital does not have or does not have
an antibiogram
• Become a reference for hospitals in preparing
antibiograms
• Become a reference for policy makers in preparing
regulations and/or guidelines for the management of
infectious diseases
• Displays antibiogram data for bacteria that cause
infections in hospitals, including priority pathogens set
by the World Health Organization 2015.
POLA BAKTERI DAN ANTIBIOGRAM SEMUA RUMAH
SAKIT BERDASARKAN JENIS SPESIMEN TAHUN 2021
All hospital blood specimen
antibiograms in 2021
 Antibiogram possible contaminant dari spesimen darah semua rumah
sakit tahun 2021

Bakteri di atas berpotensi sebagai

kontaminan karena merupakan
bagian dari flora nomal kulit, Bakteri
ini dapat dipertimbangkan sebagai
penyebab infeksi terutama jika
ditemukan pada lebih dari satu set
kultur darah atau disesuaikan
dengan gejala klinis secara hati-hati,
sebelum memutuskan terapi
antibiotik, perlu mempertimbangkan
kondisi klinis pasien dan melakukan
diskusi dengan klinisi.
 WHO priority pathogens
• Klebsiella pneumoniae resistant to 3rd generation
cephalosporin
• Escherichia coli resistant to 3rd generation cephalosporin
• carbapenem-resistant Klebsiella pneumoniae
• carbapenem-resistant Escherichia coli,
• Carbapenem-resistant Acinetobacter baumannii
• Carbapenem-resistant Pseudomonas aeruginosa
• Methicillin resistant Staphylococcus aureus (MRSA)
Distribution of WHO Top Priority Pathogens
from all specimens in all hospitals in 2020
 Distribution of WHO priority pathogens
based on specimens in all hospitals in 2021
Comparison of WHO Top Priority Pathogen
Distribution from all specimens in Class A
and Class B Hospitals in 2020
Distribution of WHO priority pathogens based on
specimens in class A, B and C hospitals in 2021
 Summary
• Antibiogram: periodic summary of antimicrobial
susceptibilities of local bacterial isolates obtained from
specimens submitted to the Clinical Microbiology
Laboratory

• Antibiograms are used:

• selecting empiric antibiotic therapy
• monitoring resistance trends
• compare susceptibility rates across institutions
and track resistance trends.
 Summary
Microbiology Lab →clinical impact
• Quality is a must
• Susceptibility test: selective
reporting
• Faster is better, but good
interpreting result is important
• Communication with clinician
should be encourage
# Stay Healthy
# Stay Safe