424

IHMA, Inc.2122 Palmer Drive

Schaumburg, IL 60173 USACharacterization and Profiling of Multi-Drug Resistant (MDR) Enterobacteriaceae From Latin America

424 Schaumburg, IL 60173 USAPhone: +1.847.303.5003Fax: +1.847.303.5601

www.ihmainc.com

Characterization and Profiling of Multi-Drug Resistant (MDR) Enterobacteriaceae From Latin AmericaM. Renteria1, D. Sahm1, S. Bouchillon1, H. Leister-Tebbe2

1International Health Management Associates, Inc., Schaumburg, IL, USA,2Pfizer Inc., Collegeville, PA, USA

• High MDR Enterobacteriaceae rates wereobserved in Latin American countries

Results SummaryResultsBackground: Enterobacteriaceae species are important pathogens responsible for a widevariety of serious infections involving the bloodstream, the lower respiratory tract, theurinary tract, and other body sites. The tendency of these organisms to develop or acquireresistance to key antimicrobials can lead to MDR strains for which the therapeutic choices

Revised AbstractFigure 4. Patient Location Distribution of MDR Enterobacteriaceae Table 2. Antimicrobial Susceptibility Profiles for

MDR Enterobacteriaceae by CountryRegion Drug %S %I %R MIC50 MIC90

Figure 1. Country Distribution of MDR Enterobacteriaceae

observed in Latin American countriesranging from 68% (Honduras) down to39% (Venezuela) (Figure 1).

• Based on % susceptibility tigecycline wasthe most active drug against MDR

resistance to key antimicrobials can lead to MDR strains for which the therapeutic choicesbecome limited. Therefore, tracking and profiling MDR strains is an important aspect ofany surveillance initiative. In this study data from The Tigecycline Evaluation SurveillanceTrial (TEST) program were analyzed to evaluate the profiles and characteristics of MDRpopulations from Latin America.Methods: Between 2008 and 2013 8,716 isolates of Enterobacteriaceae from Argentina,Brazil, Chile, Colombia, El Salvador, Guatemala, Honduras, Mexico, Panama, and

Region Drug %S %I %R MIC50 MIC90

Mexico Tigecycline 95 3.8 1.2 0.5 2

(1161) Amikacin 80.2 5.4 14.4 4 > 64

Meropenem 93.1 1.5 5.4 ≤ 0.06 0.5

Cefepime 53.8 9.7 36.4 8 > 32

Pip-tazo 52.5 22.4 25.1 16 > 128

Levofloxacin 29.7 2.2 68.0 > 8 > 8

Inpatient293573%

the most active drug against MDREnterobacteriaceae collected frominpatients and outpatients, and regardlessof the country of origin [Panama andArgentina being exceptions] (Tables 1 and

Brazil, Chile, Colombia, El Salvador, Guatemala, Honduras, Mexico, Panama, andVenezuela were locally collected, identified, and susceptibility tested (broth microdilution)according to CLSI guidelines. The data were centralized at IHMA for analysis of the MDRpopulations. MDR was defined as resistance to drugs from three or more differentantimicrobial classes.Results: Of the 8,716 Enterobacteriaceae isolates 4,012 (46%) had a MDR phenotype; ofthose MDR, 73.2% were from inpatients, 21.8% were blood isolates, 18.3% were from

Levofloxacin 29.7 2.2 68.0 > 8 > 8

Colombia Tigecycline 94.6 4.3 1.1 0.5 2

(706) Amikacin 73.8 12.6 13.6 4 64

Meropenem 80.3 3.3 16.5 ≤ 0.06 16

Cefepime 60.8 7.9 31.3 4 > 32

Pip-tazo 39.9 12.6 47.5 64 > 128Outpatient465 Other-None given Argentina being exceptions] (Tables 1 and

2).

those MDR, 73.2% were from inpatients, 21.8% were blood isolates, 18.3% were fromurinary tract specimens, 17.5% were from wounds, 16.5% were from respiratory tractspecimens, and 6.8% were from intra-abdominal infections. By species, 33.5 % of MDRwere E. coli, 28.7% were K. pneumoniae, 21% were E. cloacae, and 9.1% were S.marcescens. The individual antimicrobial profiles for all Enterobacteriaceae and the MDRpopulation were as follow:

ConclusionsAll Enterobacteriaceae (8716) MDR (4012)

Pip-tazo 39.9 12.6 47.5 64 > 128

Levofloxacin 46.9 3.8 49.3 4 > 8

Argentina Tigecycline 92.2 7.0 0.7 0.5 2

(683) Amikacin 86.5 6.4 7.0 4 32

Meropenem 95.0 0.6 4.4 ≤ 0.06 0.5

Cefepime 51.7 11.6 36.8 8 > 32

Pip-tazo 43.2 18.0 38.8 32 > 128

46512%

Other-None given61215%

• The incidence of the MDR phenotypeamong Enterobacteriaceae is high in LatinAmerica, especially among inpatientisolates.

ConclusionsAll Enterobacteriaceae (8716) MDR (4012)

Drug %S MIC50 MIC90 %S MIC50 MIC90

Tigecyclinea 96.7 0.5 2 93.4 0.5 2

Pip-tazo 74.5 4 > 128 48.8 32 > 128

Amikacin 89.8 2 32 79.1 4 64

Cefepime 77 ≤ 0.5 > 32 53 8 > 32

Ceftazidime 16.8 ≤ 8 > 32 8.1 16 > 32

Figure 2. Specimen Source Distribution of MDR Enterobacteriaceae

Pip-tazo 43.2 18.0 38.8 32 > 128

Levofloxacin 37.9 6.3 55.8 8 > 8

Guatemala Tigecycline 86.2 11.0 2.8 1 4

(355) Amikacin 80.9 4.8 14.4 4 64

Meropenem 84.2 3.7 12.1 ≤ 0.06 4

Cefepime 41.4 11.0 47.6 16 > 32

isolates.

• This phenotype was found in everycountry and from isolates from everymajor body source.

Ceftazidime 16.8 ≤ 8 > 32 8.1 16 > 32

Levofloxacin 64 0.5 > 8 33.9 8 > 8

Meropenem 95.1 ≤ 0.06 0.5 89.6 ≤ 0.06 2

aFDA breakpoints used for tigecycline

Conclusions: The MDR rate among Enterobacteriaceae is very high in Latin America,

especially among inpatient isolates. The MDR phenotype was also prevalent among

isolates from the key infection sites. Meropenem and tigecycline were the most active

Table 1. Antimicrobial Susceptibility Profile for MDR Enterobacteriaceae byPatient Location

Pip-tazo 51.6 20 28.5 16 > 128

Levofloxacin 27.0 3.9 69.0 > 8 > 8

Chile Tigecycline 95.5 3.72 0.8 1 2

(242) Amikacin 66.5 7.4 26.0 8 > 64

Meropenem 90.9 4.1 5.0 ≤ 0.06 1

Cefepime 39.3 8.3 52.5 32 > 32WoundGU735

CVS87622%

IAI2747%

Others76519%

Location (n) Drug %S %I %R MIC50 MIC90

Enterobacteriaceae species are important pathogens responsible for a wide

Introduction

major body source.

• Tigecycline, amikacin, and meropenemwere the only agents with notable activityagainst the MDR phenotype

• The prevalence and critical importance of

isolates from the key infection sites. Meropenem and tigecycline were the most active

drugs against the MDR population. The critical importance of this phenotype warrants

careful and ongoing surveillance.

Cefepime 39.3 8.3 52.5 32 > 32

Pip-tazo 38.8 21.9 39.3 64 > 128

Levofloxacin 26.0 3.3 70.7 > 8 > 8

Panama Tigecycline 91.3 7.8 0.9 0.5 2

(231) Amikacin 88.7 5.63 5.6 4 32

Meropenem 97.4 0.4 2.2 ≤ 0.06 0.5

Cefepime 74.0 12.99 13.0 2 32

Wound70117%Respiratory

66117%

73518%

Location (n) Drug %S %I %R MIC50 MIC90

Inpatient Tigecycline 93.9 4.9 1.2 0.5 2

(2935) Amikacin 78.3 7.8 13.9 4 64

Meropenem 89.7 2.3 8.0 ≤ 0.06 2

Cefepime 53.1 9.8 37.1 8 > 32Enterobacteriaceae species are important pathogens responsible for a widevariety of serious infections involving the bloodstream, the lower respiratorytract, the urinary tract, and other body sites. The tendency of theseorganisms to develop or acquire resistance to key antimicrobials can lead toMDR strains for which the therapeutic choices become limited. Therefore,tracking and profiling MDR strains is an important aspect of any surveillanceinitiative. In this study data from The Tigecycline Evaluation Surveillance

• The prevalence and critical importance ofthis phenotype warrants careful andongoing surveillance, and underscoresthe need for new drugs for themanagement of infections caused by

* CVS: Cardiovascular; IAI: Intra-abdominal Infectons; GU; Genitourinary

Cefepime 74.0 12.99 13.0 2 32

Pip-tazo 62.3 19.1 18.6 8 > 128

Levofloxacin 26.0 6.06 68.0 8 > 8

Brazil Tigecycline 96.5 3.5 0 0.5 2

(229) Amikacin 76.4 10.5 13.1 4 64

Meropenem 90.8 1.3 7.9 ≤ 0.06 1

Cefepime 53.1 9.8 37.1 8 > 32

Ceftazidime 6.5 30 63.5 16 > 32

Pip-Tazo 46.1 19.1 34.8 32 > 128

Levofloxacin 35.4 4.2 60.5 8 > 8initiative. In this study data from The Tigecycline Evaluation SurveillanceTrial (TEST) program were analyzed to evaluate the profiles andcharacteristics of MDR populations from Latin America.

Materials & Methods• Between 2008 and 2013, 8,716 isolates of Enterobacteriaceae from

References and Acknowledgments:1. Clinical Laboratory Standards Institute. 2012. Methods for

management of infections caused byMDR Enterobacteriaceae.

Figure 3. Species Distribution of MDR Enterobacteriaceae

Meropenem 90.8 1.3 7.9 ≤ 0.06 1

Cefepime 37.6 7.9 54.6 32 > 32

Pip-tazo 45.4 10.9 43.7 32 > 128

Levofloxacin 35.4 3.5 61.1 8 > 8

Venezuela Tigecycline 95.9 2.7 1.4 0.5 2

(220) Amikacin 78.2 9.6 12.3 4 64

Meropenem 92.3 0.9 6.8 ≤ 0.06 0.5

Outpatient Tigecycline 91.8 6.2 1.9 0.5 2

(465) Amikacin 80.7 8.2 11.2 4 64

Meropenem 89.9 1.3 8.8 ≤ 0.06 2

Cefepime 56.1 11.0 32.9 8 > 32• Between 2008 and 2013, 8,716 isolates of Enterobacteriaceae from

Argentina, Brazil, Chile, Colombia, El Salvador, Guatemala, Honduras,Mexico, Panama, and Venezuela were locally collected, identified, andsusceptibility tested (broth microdilution) at each participating laboratoryusing sponsor-supplied broth microdilution panels.

• Organism collection, transport, confirmation of organism identification,and development and management of a centralized database were

1. Clinical Laboratory Standards Institute. 2012. Methods forDilution Antimicrobial Susceptibility Tests for Bacteria That GrowAerobically; Approved Standards -- Ninth Edition. CLSI documentM07-A9. Wayne, PA.

2. Clinical and Laboratory Standards Institute. 2014. PerformanceStandards for Antimicrobial Susceptibility Testing; Twenty-FourthInformational Supplement. CLSI Document M100-S24. Wayne,

Meropenem 92.3 0.9 6.8 ≤ 0.06 0.5

Cefepime 67.7 12.3 20 4 > 32

Pip-tazo 67.3 14.1 18.6 8 > 128

Levofloxacin 35.5 4.1 60.5 8 > 8

El Salvador Tigecycline 87.6 5.7 6.7 0.5 4

(105) Amikacin 63.8 7.6 28.6 8 > 64

E. coli134333%

K. pneumoniae115329%

Ceftazidime 8.0 36.1 55.9 16 > 32

Pip-Tazo 56.1 17.6 26.2 16 > 128

Levofloxacin 28.0 3.7 68.4 > 8 > 8

None given Tigecycline 92.3 6.7 1.0 0.5 2

We gratefully acknowledge the contributions of the investigators,laboratory personnel, and all members of the Tigecycline

and development and management of a centralized database werecoordinated by International Health Management Associates, Inc. locatedin Schaumburg, IL, USA. The data were centralized at IHMA for analysisof the MDR populations. MDR was defined as resistance to drugs fromthree or more different antimicrobial classes.

• Minimum inhibitory concentrations (MICs) were determined by theClinical and Laboratory Standards Institute (CLSI) recommended brothmicrodilution testing method using MicroScan (Siemens Medical

Informational Supplement. CLSI Document M100-S24. Wayne,PA.

3. Tygacil®, 2010. Federal Drug Administration, ProductInformation. Pfizer Inc., Collegeville, PA, USA.

Meropenem 71.4 6.7 21.9 ≤ 0.06 16

Cefepime 33.3 15.2 51.4 32 > 32

Pip-tazo 49.5 21.0 29.5 32 > 128

Levofloxacin 9.5 2.9 87.6 > 8 > 8

Honduras Tigecycline 92.5 7.5 0 0.5 2

(80) Amikacin 77.5 15 7.5 4 32

E. cloacae84121%S. marcescens

3669%

Others

(612) Amikacin 81.7 6.7 11.6 4 64

Meropenem 88.9 1.5 9.6 ≤ 0.06 2

Cefepime 50.2 11.0 38.9 8 > 32

Ceftazidime 15.4 29.1 55.6 16 > 32 laboratory personnel, and all members of the TigecyclineEvaluation and Surveillance Trial group. This study wassponsored by Pfizer Inc.

microdilution testing method using MicroScan (Siemens MedicalSolutions Diagnostics, West Sacramento, CA) or Sensititre (TREKDiagnostic Systems, Cleveland, OH) panels [1]. All antimicrobics weresupplied by the panel manufacturers.

• MIC interpretive criteria followed published CLSI guidelines or FDAbreakpoints where applicable [2-3].

(80) Amikacin 77.5 15 7.5 4 32

Meropenem 83.8 3.8 12.5 ≤ 0.06 4

Cefepime 46.3 10 43.8 16 > 32

Pip-tazo 56.3 16.3 27.5 16 > 128

Levofloxacin 45 6.3 48.8 4 > 8E. aerogenes1804%

K. oxytoca682%

Others612%

Ceftazidime 15.4 29.1 55.6 16 > 32

Pip-Tazo 56.2 14.4 29.4 16 > 128

Levofloxacin 31.2 2.9 65.9 > 8 > 8