Trends and molecular characterization on Extended Spectrum Beta-Lactamase (ESBL) in Enterobacteriaceae in intrababdominal and urinary tract infections in Dominican Republic. The SMART Study 2009-2013 Rodriguez-Taveras, Carlos (1); Gil, Yocasta (2); Manfred Lutz (3) 1. Infectious Diseases Division, Internal Medicine Department, Hospital Central de Las Fuerzas Armadas, Santo Domingo, Dominican Republic. 2. Formerly at MSD Central America and Dominican Republic, Panamá. 3. MSD Caribbean Region, Costa Rica

Graph 3 Graph 2 p , Introduction and purpose Results Susceptibility trends of E. coli Distribution of Pathogens, 2013 (all sites) 1.4% 2.0% 0.7% 100 2.0% SMART Study was initiated by Merck in 2002 to monitor the in 675 isolates were obtained, 568 (84.1%) were Enterobacteriacea, 2009 (n=34) 3.4% 2010 (n=85) mainly E coli (48.6%), Klebsiella pneumoniae and 90 4.1% Escherichia coli (n=72) vitro susceptibility of clinical aerobic and facultative gram-negative 2011 (n=70) bacterial isolates from intra-abdominal infections (IAI) to mirabilis (≤10.0%). E. coli ESBL producers with an increasing 80 2012 (n=57) Pseudomonas aeruginosa (n=18 2013 (n=72) ertapenem and 11 other selected antimicrobials internationally, trend ranging from 15% in 2009 to 60% in 2012 and declining to 70 Klebsiella pneumoniae (n=15) ETP=ertapenem 6.1% enabling longitudinal analyses to determine if susceptibility 40% in 2013 The main molecular type of ESBL was the CTX-M of 60 IPM=imipenem (n=14) FEP=cefepime patterns change over time. Collection of isolates from Dominican the ESBL, and less frequent SHV type. The plasmidic AmpC β- 50 CTX=cefotaxime Morganella morganii (n=9) FOX= lactamases type was present mainly in 1212 (6%) and 2013 (2%). CAZ= 48.6% Republic started in late 2008. Data for this study is from 2009- 40 CRO=ceftriaxone 9.5% Enterobacter cloacae (n=6) % Susceptible% 2013. Data was retrieved from the SMART database on December SAM=-sulbactam 30 TZP=-tazobactam Klebsiella oxytoca (n=5) Table 1 AMK= 11, 2014. CIP=ciprofloxacin 20 Acinetobacter baumannii (n=3) Number of isolates submitted by source, 2009- LVX=levofloxacin Objective: To describe the molecular trends on Extended 10.1% Proteus penneri (n=3) 2013 10 Spectrum Beta-Lactamase (ESBL) in Enterobacteriaceae in * Significant decreasing trend (p<0.05) Serratia marcescens (n=2) intrabdominal and urinary tract infections in Dominican Republic. 0 2009 2010 2011 2012 2013 Total ETP IPM FEP* CTX* FOX CAZ* CRO* SAM TZP AMK CIP* LVX* (n=1) IAI 95 96 90 99 99 479 12.2% UTI 50 47 50 49 196 All sources 95 146 137 149 148 675 Materials & Methods Graph 3 Trends in ESBL+ rates of E. coli, 2009-2013 Conclusion 100 intra-abdominal strains from 2009-2013 and 50 UTI strains from 2010-2013 were included. Susceptibility and ESBL status 100 A high rate of ESBL Enterobactariaceae is present in Dominican Republic were determined using the CLSI broth microdilution method. MIC Graph 1 90 in intraabdominal and urinary tract infections, higher than reported in 80 interpretive criteria followed the 2014 M100-S24 guidelines of the Trends of β-lactamases in Enterobacteriaceae. SMART Study for the rest of Latin America. CTX-M is the most prevalent 70 ESBL in these group and the plasmidic AmpC β-lactamases is present in CLSI. For cefepime versus Enterobacteriaceae (E coli and 2009-2013 (all sources) 60 smaller proportion. Klebsiella pneumoniae) for which the susceptible-dose dependent Dominican Republic, 2009-2013 (all sources) 50 % ESBL+ Dominican Republic* (SDD) interpretive category has replaced the intermediate 40 40 Latin America* category, M100-S23 criteria were used to maintain the intermediate 30 Limitations category for analysis. The susceptibility of all gram-negative 35 20 There was only one site for the SMART data in Dominican Republic isolates combined was calculated using breakpoints appropriate for * Significant increasing 30 10 trend (p<0.05) each species and assuming 0% susceptible for species with no 0 25 breakpoints for any given drug. Genes encoding ESBLs (TEM, 2009 (34/992) 2010 (85/1914) 2011 (70/2024) 2012 (57/2191) 2013 (72/1946) Year (n Dominican Republic/n Latin America) SHV, CTX-M-type), carbapenemases (KPC, NDM, IMP, VIM, OXA- 20 Acknowledgements

48-type), and plasmidic AmpC β-lactamases ( CMY, DHA, FOX, Enterobacteriaceae 15 We acknowledge the contributions of Elkin Lemos for consolidating this data and MOX, ACC, MIR, ACT) were detected using a combination of Homero Monsanto for his review in this project 10 2009 (n=73) microarray (Check-MDR CT101, Check-Points B.V., Wageningen, % of all 5 2010 (n=132) the Netherlands) and multiplex PCR assays. 2011 (n=118) 0 2012 (n=118)

CTX-M SHV ESBL TEM ESBL KPC OXA C'ase NDM AmpC 2013 (n=127) Disclosure This study was sponsored by MSD Central America and the Caribbean

Printed by