It More Fun Doing the Antibiogram:
Proper Analysis and Optimization of
Antibiotic Use using the Antibiogram
Ma. Charmian M. Hufano, MD, FPCP, FPSMID
Infectious Disease Specialist
Lecture Outline
• The importance of a hospital antibiogram
• How to create your hospital antibiogram
• How to translate the science of your hospital antibiogram in action
5
6
22 Sentinel sites in14 regions of the Philippines
Antimicrobial Resistance Surveillance Reference
Laboratory
ANNUAL REPORT
ANTIMICROBIAL RESISTANCE SURVEILLANCE PROGRAM 2013 DATA SUMMARY REPORT
ANTIMCROBIAL RESISTANCE SURVEILLANCE REFERENCE LABORATORY
Yearly resistance rates of
Staphylococcus aureus, ARSP, 2005-2014
7
http://www.ritm.gov.ph
33.5 37 35.6 36.1
46 54.3 52.7
56.6 53.2 60.3
0
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
% R
esis
tan
ce
Penicillin
Oxacillin
Vancomycin
Percent Resistance of Pseudomonas aeruginosa, ARSP,
2014
14.5 15.6
13.4 13.2
17.5 15.8
9.5
16.3 15.6
0
5
10
15
20
25
30
Pip/Tazobactam Ceftazidime Cefepime Aztreonam Imipenem Meropenem Amikacin Gentamin Ciprofloxacin
% R
esis
tan
ce
Antibiotics
n=3706 n=4108 n=3861 n=3119 n=3997 n=3725 n=3971 n=3892 n=3926
Pseudomonas aeruginosa MDR and possible XDR rates,
ARSP, 2014
Acinetobacter baumannii
No. of Organisms % MDR % possible XDR
All isolates 4286 23% 18%
Blood culture isolates 259 35% 26%
2013 MDR Pseudomonas = 22%
2013 XDR Pseudomonas = 13%
Percentage resistance of urinary Escherichia coli from
outpatient versus inpatient, ARSP, 2014
Antimicrobial Outpatient Inpatient
Oral Agents N %R N %R
Ampicillin 971 79.8 1936 82.3
Co-amoxiclav 1084 18.5 2226 24.2
Cefuroxime 535 24.3 949 35.2
Ciprofloxacin 979 50.7 2073 43.1
Cotrimoxazole 1012 65.8 1966 68
Nitrofurantoin 945 6.6 1757 5.5
Percentage resistance of urinary Escherichia coli from
outpatient versus inpatient, ARSP, 2014
Antimicrobial Outpatient Inpatient
Intravenous Agents N %R N %R
Piperacillin/Tazobactam 1037 3.1 2078 6
Ceftriaxone 917 27.5 2007 38.2
Ertapenem 554 1.3 1300 2.8
Amikacin 941 2.2 1897 3.9
Legend: N=number tested; %R=percentage resistance; Outpatient=specimen taken from patients at the outpatient
Department or emergency room; Inpatient=specimen taken from patient admitted or hospitalized
MRSA Rates by Site, ARSP
2014
2014 Data Summary Report Antimicrobial Resistance Surveillance Program - Philippines
29
FIGURE 34. Yearly clindamycin, co-trimoxazole and
tetracycline resistance rates of S. aureus, ARSP,
2005-2014
Methicillin-resistant Staphylococcus aureus
(MRSA)
There were 2,004 MRSA isolates reported from the
ARSP sentinel sites for 2014. Most of these iso-
lates were isolated from cutaneous and blood cul-
ture isolates. The overall cumulative MRSA rate
for 2014 was at 60.3%. Sentinel site MRSA rates
ranged from as low as 24.8% (NKI, n=137) to as
high as 74.5% (LCP, n=31). FIGURE 36 shows the
MRSA rates by region.
Of these 2014 MRSA isolates, 85% were from
specimens taken from patients in the outpatient
department, emergency room and admissions
within their 1st 2 hospital days. When MRSA rates
were analyzed by specimen type, 60% of all blood
isolates (n=570) and 64.7% of all skin and soft tis-
sue isolates (n=1,535) were methicillin-resistant.
Resistance rate of the MRSA isolates against avail-
able agents for treatment showed variable suscep-
tibility to available antimicrobial agents as seen in
FIGURE 35. Resistance rates have increased signifi-
cantly for most of the antibiotics tested when
compared to 2013 rates: rifampin from 4% in 2013
to 6% in 2014 (p value 0.0339); ciprofloxacin from
7% in 2013 to 10.5% in 2014 (p value 0.0017); co-
trimoxazole from 18% in 2013 to 26.1% in 2014 (p
value 0.0001); clindamycin from 12% in 2013 to
14.6% in 2014 (p value 0.0353); and tetracycline
form 8% in 2013 to 10.9% in 2014 (p value 0.0103).
The 2014 MRSA isolates rates of resistance did not
differ significantly against erythromycin, linezolid
and vancomycin from reported rates in 2013 (p
value > 0.05).
FIGURE 35. Percentage resistance of MRSA, ARSP,
2014
Figure 36. MRSA rates by sentinel site region
MRSA rates by site, ARSP 2014
2014 Data Summary Report Antimicrobial Resistance Surveillance Program - Philippines
35
FIGURE 48. Yearly carbapenems and amikacin re-
sistance of Klebsiella species, ARSP, 2005-2014
Extended-spectrum β- lactamase-producing
Enterobacteriaceae
Extended-spectrum β- lactamases (ESBLs) are en-
zymes that mediate resistance to extended-
spectrum cephalosporins and monobactams but
do not affect cephamycins or carbapenems. [7]
Using ceftazidime disk diffusion as initial screen-
ing for ESBL production, out of 5,506 E. coli iso-
lates tested, 25% screened positive (ESBL suspect).
Similarly, 7,464 Klebsiella species isolates were test-
ed and 35.7% screened positive for ESBL produc-
tion. Of the subset of 267 ESBL-suspect E. coli iso-
lates sent to the reference laboratory 48% were
confirmed by phenotypic testing as ESBL-
producing E. coli. Likewise, of the subset of 512
ESBL-suspect Klebsiella species isolates sent to the
reference laboratory 50.4% were confirmed by
phenotypic testing as ESBL-producing Klebsiella
species.
Comparing 2014 E. coli ESBL-suspect rates from
sentinel sites with at least 30 isolates tested, re-
ports were variable with lowest rate reported by
RTM at 9.4% (n=32) while highest ESBL-suspect
rate noted from STU at 51.6% (n=153) as seen in
FIGURE 49. Comparing 2014 Klebsiella species
ESBL-suspect rates from sentinel sites with at least
30 isolates tested, reports were variable with low-
est rate reported by BGH at 11.7% (n=496) while
highest ESBL-suspect rate noted from STU at
78.4% (n=88) as seen in FIGURE 50.
FIGURE 49. Percentage of ESBL-suspect
(ceftazidime-resistant) E. coli, ARSP, 2014
FIGURE 50. Percentage of ESBL-suspect
(ceftazidime-resistant) Klebsiella species, ARSP,
2014
ARSP 2014
Why do we need hospital antibiograms?
• With increasing antimicrobial resistance worldwide, it is crucial to monitor
emerging trends in drug resistance at the local level to support clinical
decision making, infection-control interventions, and antimicrobial-resistance
containment strategies
• Several distinct approaches can be used in summarizing results from a
database of clinical isolates, but, unfortunately, results obtained using
different calculation algorithms may not necessarily be comparable.
Clinical Laboratory Standards Institute
Antibiogram
• Cumulative antimicrobial susceptibility test data summary.
• Report generated by analysis of results on insolates from a particular
institution(s) in a defined period of time that reflects the percentage of first
isolates (per patient) of a given species that is susceptible to each of the
antimicrobial agents routinely tested.
• Guide clinicians in the selection of initial empiric antimicrobial therapy for
infection
CLSI Recommendations
• Information System Design- computer application to analyze cumulative
AST data
• Integrated into LIS or system must have the capability to send data through a real-time
interface or to periodically export results to an analysis program
• Software must be versatile and flexible and have the ability to analyze data for a defined
period to generate cumulative statistics and line listings; and rem
WHONET is a free
Windows-based
database software
developed for the
management and
analysis of
microbiology
laboratory data with a
special focus on the
analysis of AST
results..
CLSI Recommendations
DATA VERIFICATION
• Only final, verified results should be included.
-Viridans streptococci resistant to penicillin
-Vancomycin-resistant Staphylococcus aureus
CLSI Recommendations
FACILITY
• Antibiogram reports should be institute specific.
FREQUENCY
• Analyze and report antibiogram data at least once a year.
CLSI Recommendations
ISOLATES
• Include only species with testing data for at least 30 isolates.
• Include only the 1st isolate of a given species per patient per analysis period irrespective of body site, AST profile or other phenotypic characteristics.
• Include diagnostic, not surveillance isolates.
CLSI Recommendations
ANTIMICROBIAL AGENTS
• Include results only for drugs that are routinely tested.
• AST results for antimicrobials tested against drug-resistant strains are generally biased towards higher rates of AMR
• Results of supplemental drugs tested only from drug-resistant pathogens are not included in to the antibiogram report.
CLSI Recommendations
CALCULATIONS
• Calculate percentage susceptibility. Do not include the percentage of isolates with intermediate susceptibility.
• Perform calculations using the interpretive breakpoints and rules current at the time of analysis. Analysis of historical data require the storage of quantitative test measurements with reinterpretation of results using interpretive criteria or breakpoints current at the time of analysis.
Supplemental Analysis
• Streptococcus pneumoniae and reporting of meningitis and non-meningitis
breakpoints
Antimicrobial Resistance Surveillance Program - Philippines 2014 Data Summary Report
20
FIGURE 6. Percent resistance of S. pneumoniae,
ARSP, 2014
FIGURE 7. S. pneumoniae penicillin-resistance rates
by specimen type, ARSP, 2014
FIGURE 8. Yearly resistance rates of S. pneumoniae,
ARSP, 2005-2014
Streptococcus pneumoniae Serotypes
Serotyping of S. pneumoniae isolates referred to
the reference laboratory was done to identify local
prevailing serotype distribution. The method em-
ployed in the reference laboratory for pneumo-
cocci serotyping is the slide agglutination test
(Denka Seiken). For 2014, there were 44 invasive
(blood and CSF) and 74 non-invasive (respiratory
and other non-invasive specimens) pneumococci
isolates sent to the national reference laboratory
for confirmatory testing and serotyping. The com-
monest serotypes from the blood and CSF isolates
were serogroup/serotypes 5, 1, 4 and 6 compris-
ing 64% of the referrals (FIGURE 9). Invasive
serogroup/serotypes 4, 5 and 15 were associated
with penicillin-resistance in the 2014 data. In con-
trast, most common serotypes from non-invasive
isolates were: serogroup/serotype 3, 19 and 7
comprising 35% of the non-invasive referrals as
seen in FIGURE 10. There were 3 invasive and 8
non-invasive isolates which were non-typable.
FIGURE 9. Distribution of invasive S. pneumoniae
isolates by serogroup/serotypes, ARSP, 2014
FIGURE 10. Distribution of non-invasive S. pneu-
moniae isolates by serogroups/serotypes, ARSP,
2014
CLSI M100; 2015
ARSP 2014 Annual Report. S. pneumoniae %R to penicillin
Supplemental Analysis
• Staphylococcus aureus- List %S for ALL and MRSA subset
11
22
9.1
14.6
26.1
10.9
0
5
10
15
20
25
30
Clindamycin Co-trimoxazole Tetracycline
Staphylococcus aureus and MRSA %R, ARSP 2014
S. aureus MRSA
ARSP Annual Report, 2014
Additional Data Stratification
By nursing unit or site of care
By organism’s resistance characteristics
By specimen type or infection site
By clinical service or patient population
Additional Data Stratification
By nursing unit or site of care
By organism’s resistance characteristics
By specimen type or infection site
By clinical service or patient population
-by patient location at time
that infection is suspected or
diagnosed
-e.g. ICU versus wards versus
OPD
-Antibiogram for specific data
set maybe used to develop
treatment algorithms specific
for patients at that particular
unit or site of infection
Staphylococcus aureus by Patient Location
CLSI M39-A3
Comparison of unit –specific and hospital-wide
antibiograms: potential implications for selection of
empirical antimicrobial therapy
SETTING: A 625-bed tertiary care medical center.
METHODS: Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was
recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram.
Binkley S etal. Infec Control Hosp Epidemiol 2006 Jul;27(7):682-7.
Comparison of unit –specific and hospital-wide
antibiograms: potential implications for selection of
empirical antimicrobial therapy
RESULTS: A total of 9,970 bacterial isolates were evaluated in this study,
including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates,
and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial
isolates resistant to antimicrobials were significantly higher in the medical
ICU and surgical ICU than the hospital-wide antibiogram would have
predicted, whereas the percentages of isolates susceptible to antimicrobials
were significantly higher in the non-ICU units, compared with the hospital
overall. However, on general medicine units, the prevalence of susceptibility to
levofloxacin was significantly lower than that for the hospital overall.
Binkley S etal. Infec Control Hosp Epidemiol 2006 Jul;27(7):682-7.
Comparison of unit –specific and hospital-wide
antibiograms: potential implications for selection of
empirical antimicrobial therapy CONCLUSIONS: Unit-specific antibiograms are important for making informed
decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram
may mask important differences in susceptibility rates across different units. These
differences may have important implications for selecting the optimal empirical
antimicrobial therapy.
Binkley S etal. Infec Control Hosp Epidemiol 2006 Jul;27(7):682-7.
Additional Data Stratification
By nursing unit or site of care
By organism’s resistance characteristics
By specimen type or infection site
By clinical service or patient population
-data are segregated by
resistance characteristics of a
given organism
-Useful for MDROs
Staphylococcus aureus %S, CLSI M39-A3
Klebsiella pneumoniae %S, CLSI M39-A3
Additional Data Stratification
By nursing unit or site of care
By organism’s resistance characteristics
By specimen type or infection site
By clinical service or patient population
-by specimen type or infection
site (e.g. urine isolates, blood
isolates)
Urine Isolates from Inpatients and Outpatients
for Selected Uropathogens
CLSI M39-A3
Urine Isolates from Inpatients and Outpatients
for Selected Uropathogens
CLSI M39-A3
Additional Data Stratification
By nursing unit or site of care
By organism’s resistance characteristics
By specimen type or infection site
By clinical service or patient population
-by clinical service, medical or
surgical specialty or specific
patient population (e.g.
transplant, burn, pediatrics)
Isolates from All Sites for Selected Pathogens
for Burn Patients
CLSI M39-A3
Examining Percent Susceptible for
Combinations of Antimicrobial Agents
• For guiding empiric therapy of infections where the likely causative agent are
best treated with a combination of antimicrobial agents, it maybe useful to
examine the percentage of isolates susceptible to 1 or both drugs in relevant
combinations.
CLSI M39-A3
% SUSCEPTIBLE
No of
strains
CIP CTZ IPM TOB CTZ
&/
CIP
IMP
&/
CIP
CTZ
&/
TOB
IMP
&/
TOB
PAE 814 69 80 79 86 86 84 91 91
Pseudomonas aeruginosa susceptibility rates for monotherapy and select combination drug therapy
CIP- ciprofloxacin; CTZ- ceftazidime; IPM- imipenem; TOB- tobramycin
CLSI M39-A3
Utility of a Combination Antibiogram for
Treating Pseudomonas aeruginosa
• A retrospective observational study at a Veterans Affairs (VA) hospital in the
Southwestern region of the U.S. was conducted.
• P. aeruginosa isolates were collected between January 2008 and February 2012
in hospitalized veterans.
• A total of 374 isolates were included, of which 61 (16%) were obtained from
the ICU.
Thurman L etal. Am Journal of Infec Ds 10(2):88-94,2014
Utility of a Combination Antibiogram for
Treating Pseudomonas aeruginosa
Susceptibility rates for monotherapy with a beta-lactam ranged from 83.7 to 90.6%.
Collectively, all P. aeruginosa isolates benefited in coverage with the addition of a
fluoroquinolone or an aminoglycoside to one of the beta-lactams considered for monotherapy
(p<0.01 for each comparison).
Monotherapy with a beta-lactam could be considered for mild to moderate wound infections
which had beta-lactam susceptibility rates greater than 90% and the addition of a
fluoroquinolone did not significantly extend the spectrum.
Combination susceptibility rates ranged from 89.0 to 99.2%. Dual therapy of a beta-lactam
with amikacin or tobramycin resulted in significantly better coverage than with a
fluoroquinolone (p<0.03 for all combinations).
Thurman L etal. Am Journal of Infec Ds 10(2):88-94,2014
Utility of a Combination Antibiogram for
Treating Pseudomonas aeruginosa
For severe infections dual therapy with tobramycin or amikacin may be preferred over
fluoroquinolones, but the risks versus benefits of aminoglycoside therapy must be weighed for
each patient.
In conclusion, combination antibiograms are useful for evaluating the treatment of P.
aeruginosa. Choosing the ideal antibiotic regimen ultimately deals with many factors and results
of this combination antibiogram are only specific to this institution.
Thurman L etal. Am Journal of Infec Ds 10(2):88-94,2014
CLSI M39-A3
Inclusive dates of
report
Name of Laboratory
Comments on Methods
List organisms
alphabetically, by
organism group and by
prevalence
Separate table for gram
+ and gram –
Number of organisms-
30 or more
Antibiotic names
spelled out or
abbreviations listed
%S; use dash (-) no
tested
Use of Antibiogram
• Only be used as a general guide for empirical therapy until such time that specific antimicrobial susceptibility test results on a given patient’s isolates become available.
• Other factors: the organism, the antimicrobial agent and the clinical context
• Distribution of the Report
• Pocket Guides
• Website application or PDF
• Educational lectures
CLSI: Limitations of Data, Data Analysis and
Data Presentation
• Culturing practices
• Biased by more frequent sampling of patients with treatment failure following prior antibiotic therapy; and or prolonged medical histories or recent hospitalization
• Influence of small number of isolates
• Ways to improve guidance for antimicrobial therapy when # tested isolates is small:
• Combine data on organism from data collected over more than 12 months
• Combine data, when applicable, for more than1 species within a genus
• Combine data from several comparable institutions in a geographic area
• Providing data from published summaries and guides
CLSI: Limitations of Data, Data Analysis and
Data Presentation
• Comparing results of individual antimicrobial agent results
• Comparing antibiotic susceptibility tested against all specimens versus that tested only
for urine isolates
• Identification of new patterns of resistance
• When 1st isolate per patient is used in summaries, changes related to emergence of new
patterns of resistance maybe missed
Implementing an Antibiotic Stewardship Program:
Guidelines by the IDSA and the SHEA
• We suggest development of stratified antibiograms over solely relying on
non-stratified antibiograms to assist ASPs in developing guidelines for
empiric therapy (weak recommendation, low-quality evidence)
CID; Feb 2016
Summary
• Hospital antibiograms are useful tools that clinicians can use to guide empiric
antibiotic therapy.
• Guidelines to improve representation of true susceptibility rates of common
pathogens causing infections are provided by the CLSI.
• Translating and communicating the antibiogram data remains one of the key
strategies in improving rational antibiotic use.
• No declarations of competing interests
• Acknowledgement to the Antimicrobial Resistance Surveillance Reference
Laboratory and our partner sentinel sites