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BACKGROUND Despite a reported worldwide increase, the incidence of extended-spectrum β-lactamase (ESBL) Escherichia coli and Klebsiella infections in the United States is unknown. Understanding the incidence and trends of ESBL infections will aid in directing research and prevention efforts. OBJECTIVE To perform a literature review to identify the incidence of ESBL-producing E. coli and Klebsiella infections in the United States. DESIGN Systematic literature review. METHODS MEDLINE via Ovid, CINAHL, Cochrane library, NHS Economic Evaluation Database, Web of Science, and Scopus were searched for multicenter (≥2 sites), US studies published between 2000 and 2015 that evaluated the incidence of ESBL-E. coli or ESBL-Klebsiella infections. We excluded studies that examined resistance rates alone or did not have a denominator that included uninfected patients such as patient days, device days, number of admissions, or number of discharges. Additionally, articles that were not written in English, contained duplicated data, or pertained to ESBL organisms from food, animals, or the environment were excluded. RESULTS Among 51,419 studies examined, 9 were included for review. Incidence rates differed by patient population, time, and ESBL definition and ranged from 0 infections per 100,000 patient days to 16.64 infections per 10,000 discharges and incidence rates increased over time from 1997 to 2011. Rates were slightly higher for ESBL-Klebsiella infections than for ESBL-E. coli infections. CONCLUSION The incidence of ESBL-E. coli and ESBL-Klebsiella infections in the United States has increased, with slightly higher rates of ESBL-Klebsiella infections. Appropriate estimates of ESBL infections when coupled with other mechanisms of resistance will allow for the appropriate targeting of resources toward research, drug discovery, antimicrobial stewardship, and infection prevention. Infect Control Hosp Epidemiol 2017;38:1209-1215.

Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms ( n = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. Pseudomonas aeruginosa and Klebsiella spp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active against P. aeruginosa ( n = 3,402; MIC 50 /MIC 90 , 2 and 4 μg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active against Enterobacteriaceae (MIC 50 /MIC 90 , 0.12 and 0.5 μg/ml; 99.9% susceptible), including carbapenem-resistant Enterobacteriaceae (CRE) ( n = 189; MIC 50 /MIC 90 , 0.5 and 2 μg/ml; 98.0% susceptible) and multidrug-resistant (MDR) ( n = 674; MIC 50 /MIC 90 , 0.25 and 1 μg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) ( n = 156; MIC 50 /MIC 90 , 0.5 and 2 μg/ml; 98.1% susceptible) Enterobacteriaceae isolates, as well as Klebsiella species isolates showing an extended-spectrum β-lactamase (ESBL) screening-positive phenotype ( n = 433; MIC 50 /MIC 90 , 0.25 and 1 μg/ml; 99.5% susceptible). Among Enterobacter spp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common β-lactamases detected among Klebsiella pneumoniae and E. coli isolates were K. pneumoniae carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209 Enterobacteriaceae isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 μg/ml and five isolates with ceftazidime-avibactam MIC values of 16 μg/ml and negative results for all β-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP., (Copyright © 2017 American Society for Microbiology.)

This article presents prevalence and susceptibility data from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program in Europe (1997-2004) and the United States (1999-2004) for Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL) and/or AmpC beta-lactamases. For ESBL-producing isolates, the prevalence of Escherichia coli and Klebsiella spp. in Europe and Enterobacter spp. in the United States increased over time. For AmpC-producing isolates, the prevalence of Enterobacter spp. and Citrobacter spp. decreased over time in Europe and the United States, respectively. Compared with other antimicrobial agents, meropenem and imipenem had greatest activity against ESBL-producing E. coli and Klebsiella spp. in both Europe (96.9-100.0%) and the United States (100.0%). Such activity was also found for AmpC-producing Enterobacteriaceae in Europe (50.0-100.0%), and Enterobacter spp. and Citrobacter spp. from the United States (100.0% for both). The continued efficacy of carbapenems such as meropenem confirms that these remain first-line agents for treatment of nosocomial infections caused by Enterobacteriaceae-producing ESBL or AmpC beta-lactamases.

beta-Lactamase gene promoters of 45 clinical Klebsiella oxytoca isolates resistant to beta-lactams and exhibiting beta-lactamase hyperproduction differed from those in 26 susceptible strains. Direct sequencing revealed one mutation in either the -10 or -35 conserved sequences: a G-to-A transition of the fifth base (67%) or a G-to-T transversion of the first base of the -10 sequence (27%) or a T-to-A transversion in the fourth base in the -35 sequence (4%). One strain carried both the -10 transition and the -35 transversion.