To review the epidemiology of nosocomial extended spectrum β-lactamase-producing Enterobacteriaceae in Latin America, a systematic search of the biomedical literature (PubMed) was performed for articles published since 2005. Rates of nosocomial infections caused by extended spectrum β-lactamase-producing Enterobacteriaceae in Latin America have increased since 2005. Up to 32% of Escherichia coli and up to 58% of Klebsiella pneumoniae isolates are extended spectrum β-lactamase-positive, rates that are higher than in other world regions. From a region-wide perspective, 11-25% of E. coli isolates and 45-53% of K. pneumoniae isolates were nonsusceptible to third-generation cephalosporins. At the country level, there was a wide range in Enterobacteriaceae resistance rates to third-generation cephalosporins, with especially high rates of resistance to E. coli in Guatemala, Honduras, and Mexico, and high resistance rates to Klebsiella spp. in Argentina, Brazil, Chile, Guatemala, Honduras, and Paraguay. Susceptibility of extended spectrum β-lactamase-producing Enterobacteriaceae to cefepime, fluoroquinolones, ampicillin/sulbactam, aminoglycosides, and piperacillin/tazobactam has also been compromised, leaving the carbapenems, tigecycline, and colistin as the only antibiotics with >90% susceptibility rates. There is a steady increase in the prevalence and types of extended spectrum β-lactamases produced by Enterobacteriaceae isolates in Latin American hospitals (particularly CTX-Ms), suggesting endemic conditions overlaid by clonal outbreaks. Appropriate treatment decisions and infection control strategies informed by surveillance of regional and local susceptibilities and mechanisms of resistance are required to mitigate this major public health concern.

OBJECTIVES: This study was designed to simulate standard and optimized dosing regimens for intravenous antibiotics against contemporary populations of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa using MIC distribution data to determine which of the tested carbapenem regimens provided the greatest opportunity for obtaining maximal pharmacodynamic (PD) activity. METHODS: The isolates studied were obtained from the COMPACT-COLOMBIA surveillance program conducted between February and November 2009. Antimicrobial susceptibility testing was conducted by broth microdilution method according to the CLSI guidelines. Doripenem, imipenem-cilastatin, and meropenem, were the modeled antibiotics. A 5,000 patient Monte Carlo simulation was performed for each regimen and PD targets were defined as free drug concentrations above the MIC for at least 40% of the dosing interval. RESULTS: All carbapenem regimens obtained optimal exposures against E. coli, unlike the other Enterobacteriaceae tested. Against P. aeruginosa, only a prolonged infusion of doripenem exceeded the 90% cumulative fraction of response (CFR) threshold. Worrisomely, no regimens for any of the drugs tested obtained optimal CFR against A. baumannii. For P. aeruginosa intensive care unit (ICU) isolates, CFR was approximately 20% lower for isolates collected in the respiratory tract compared with bloodstream or intra-abdominal for imipenem and meropenem. Noteworthy, all doripenem and meropenem regimens achieved greater than 90% CFR against bloodstream and respiratory isolates of K. pneumoniae. CONCLUSIONS: Our data suggests that higher dosing and prolonged infusion of doripenem or meropenem may be suitable for empirically treating ICU P. aeruginosa, while none of the carbapenems achieved optimal cumulative fraction of response against A. baumannii. Standard dosing regimens of all the carbapenems tested achieved optimal CFR against E. coli isolates, but higher carbapenem dosages might be required for empiric treatment of K. pneumoniae, particularly from an intra-abdominal source. Non-standard dosage regimens studied in this modeling should be proven effective in prospective clinical trials.

OBJECTIVES: This analysis of the Study for Monitoring Antimicrobial Resistance Trends (SMART) evaluated the susceptibility patterns of Enterobacteriaceae in Latin America in 2008, with emphasis on susceptibility trends of E. coli and K. pneumoniae. METHODS: Clinical isolates were recovered from intra-abdominal infections (IAI) from 23 centers in 10 Latin American countries. Isolates were sent to a central laboratory for confirmation of identification, antimicrobial susceptibility and ESBL testing, following the Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Of 1,003 Gram-negative bacilli collected from intra-abdominal infections, E. coli and K. pneumoniae were the most commonly isolated organisms, and 26.8% of E. coli and 37.7% of K. pneumoniae were ESBL positive. Ertapenem and imipenem were the most consistently active agents tested; 99% of ESBLpositive E. coli isolates were susceptible to ertapenem and 100% to imipenem as well, and 91% of ESBL-positive K. pneumoniae were susceptible to ertapenem and 98% to imipenem. Quinolones and cephalosporins were less active, achieving 1.5% to 76% inhibition against ESBL-producing E. coli and 3.5% to 61% inhibition against K. pneumoniae. CONCLUSIONS: Local and unit-specific surveillance data is particularly important for selection of empiric therapy and in community-acquired infections as they can help the clinician with antibiotic selection by providing guidance regarding the likely pathogens and their resistance profiles. Our data also confirm the increasing frequency with which ESBL-producing organisms are found in the community setting, with 31.4% of communityacquired and 24.9% of hospital-acquired infections found to produce ESBLs. Imipenem and ertapenem are the most active agents tested for ESBL-positive E. coli and K. pneumoniae.