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Objectives: To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by beta-lactamase genotype. Methods:Adult patients were recruited within 72h of admission to general wards of six unversity hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific beta-lactamases. Results: Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n=10), DHA (n=2)]. Risk factors for 3GCREB colonization varied by genotype. Recent antibiotic exposure and prior colonization by antibiotic-resistant bacteria were risk factors for all beta-lactamases except CTX-M-14 and CTX-M-27. Travel outside Europe was a risk factor for CTX-M-15 and CTX-M-27 [adjusted OR (aOR) 3.49, 95% CI 2.88-4.24 and aOR 2.73, 95% CI 1.68-4.43]. A previous stay in a long-term care facility was associated with CTX-M-14 (aOR 3.01, 95% CI 1.98-4.59). A preceding hospital stay in Germany increased the risk of CTX-M-15 (aOR 1.27, 95% CI 1.14-1.41), while a prior hospital stay in other European countries increased the risk of SHV-ESBL colonization (aOR 3.85, 95% CI 1.67-8.92). Conclusions: The detection of different ESBL types is associated with specific risk factor sets that might represent distinct sources of colonization and ESBL-specific dissemination routes.

As part of the multicentre Antibiotic Therapy Optimisation Study (ATHOS), minimum inhibitory concentrations (MICs) were determined for cephalosporins alone and in combination with the beta-lactamase inhibitors tazobactam, clavulanic acid and avibactam against third-generation cephalosporin-resistant Escherichia coli, Klebsiella spp. and Enterobacter spp. isolates collected in German hospitals. MIC50/90 values were 0.254mg/L for cefepime/tazobactam, 0.25-2 mg/L for ceftazidime/avibactam, 0.125-0.5mg/L for ceftaroline/avibactam, 0.5-4 mg/L for cefpodoxime/clavulanic acid and 0.25-1 mg/L for aztreonam/avibactam, depending on the underlying resistance mechanism and organism. Based on in vitro testing, beta-lactam antibiotics play an important role in the treatment of infections due to beta-lactamase-producing organisms. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

As part of the multicenter Antibiotic Therapy Optimisation Study the largest study on the prevalence of third generation cephalosporin-resistant Enterobacteriaceae carriage upon hospital admission-minimum inhibitory concentration values were generated for ampicillin/sulbactam, amoxicillin/clavulanic acid, piperacillin/tazobactam, mecillinam, mecillinam/clavulanic acid, and temocillin against third-generation cephalosporin-resistant Escherichia coli, Klebsiella species and Enterobacter species. (C) 2016 Elsevier Inc. All rights reserved.