It's More Fun Doing the Antibiogram

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..


DATA VERIFICATION

• Only final, verified results should be included.

-Viridans streptococci resistant to penicillin

-Vancomycin-resistant Staphylococcus aureus


FACILITY

• Antibiogram reports should be institute specific.

FREQUENCY

• Analyze and report antibiogram data at least once a year.


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.


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.


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






-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.



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.




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.







-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






-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






-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



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).




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.


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

CID Feb

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

Healthcare

It's More Fun Doing the Antibiogram