In-vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae isolates recovered from hospitalized patients in Germany

To evaluate the activity of ceftolozane/tazobactam compared with other broad-spectrum antimicrobials against Pseudomonas aeruginosa and Enterobacteriaceae, 497 non-duplicate P. aeruginosa and 802 Enterobacteriaceae clinical isolates were consecutively collected during the period from September 2014 to April 2015 from patients in Germany with bloodstream, lower respiratory tract, intra-abdominal or urinary tract infections. Antimicrobial susceptibility testing was performed by broth microdilution. Results were interpreted according to EUCAST criteria. Ceftolozane/tazobactam showed good activity against Escherichia coli and Klebsiella pneumoniae isolates with MIC50/90 values of 0.25/0.5 mg/L and 0.25/1 mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and meropenem MIC50/90 values were 2/8 mg/L, 0.25/8 mg/L and <= 0.03/<= 0.03 mg/L, respectively, for E. coli, and 2/16 mg/L, 0.12/8 mg/L, and <= 0.03/<= 0.03 mg/L, respectively, for K. pneumoniae isolates. The activity of ceftolozane/tazobactam against P. aeruginosa was superior to that of other antipseudomonal antimicrobials. Based on MIC50/90 values, ceftolozane/tazobactam (0.5/2 mg/L) was more active than piperacillin/tazobactam (8/64 mg/L), ceftazidime (2/16 mg/L), cefepime (2/16 mg/L) or meropenem (0.5/8 mg/L). In conclusion, ceftolozane/tazobactam exhibited the best in vitro potency of the antibiotics tested against P. aeruginosa, including isolates that were resistant to piperacillin/tazobactam, cefepime, ceftazidime, doripenem, meropenem, ciprofloxacin, levofloxacin, amikacin, and tobramycin. Ceftolozane/tazobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

Dissemination of carbapenem-resistant Pseudomonas aeruginosa isolates and their susceptibilities to ceftolozane-tazobactam in Germany

Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of this study were to determine: (i) the dissemination of carbapenem-resistant CP-negative and CP-positive PA isolates; and (ii) the in-vitro activity of ceftolozane-tazobactam (CTT) against carbapenemsusceptible and carbapenem-resistant isolates. Isolates were collected prospectively from January 2016 to April 2017 at 20 German medical laboratories. Each centre was asked to provide 50 consecutive isolates from hospitalized patients. Overall, 985 isolates were collected, of which 34% were obtained from intensive care patients. Seven hundred and thirty-eight (74.9%) isolates were susceptible to both imipenem and meropenem (Subgroup I), and 247 (25.1%) isolates were resistant to carbapenems (Subgroup II): 125 (12.7%) were imipenem-resistant but meropenem-susceptible, 12 (1.2%) were meropenem-resistant but imipenem-susceptible, and 110 (11.2%) were resistant to both carbapenems (Subgroup III). A CP was detected in 28 (2.8%) isolates (predominantly VIM-2). Nine hundred and fifty (96.4%) isolates were CTTsusceptible. Susceptibility to CTT was seen in 99.6% of Subgroup I isolates, 87% of Subgroup II isolates and 74.5% of Subgroup III isolates. Overall, 2.8% of PA produced a CP, while 22.2% were carbapenemresistant, CP-non-producing isolates. Based on these findings, CTT may be considered for treatment of PA infections, particularly those caused by multi-drug-resistant CP-non-producing isolates. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

The evolution of carbapenem resistance determinants and major epidemiological lineages among carbapenem-resistant Acinetobacter baumannii isolates in Germany, 2010-2019

The aim of this study was to investigate and compare the molecular epidemiology and carbapenem resis-tance determinants in clinical Acinetobacter baumannii isolates collected during four multicentre surveil-lance studies conducted by the Paul-Ehrlich-Society for Infection Therapy. Isolates were collected prospec-tively from hospital in-patients at 17 medical centres in Germany over four periods of three-to six -months starting in October of each of 2010, 2013, 2016 and 2019. Species identification was performed by MALDI-TOF, gyrB multiplex polymerase chain reaction (PCR), and detection of the intrinsic blaOXA-51-like gene. Minimum inhibitory concentrations were determined by broth microdilution. The prevalence of carbapenemase-encoding genes was investigated by OXA-multiplex PCR and whole-genome sequencing. Molecular epidemiology was examined by rep-PCR and core-genome multi-locus sequence typing. A to-tal of 302 A. baumannii isolates were collected. Resistance to imipenem and/or meropenem was detected in 58 isolates (19.2%) from 14 centres. The proportion of carbapenem-resistant isolates increased from 21.3% in 2010 to 33.3% in 2013, and then decreased to 13.8% in 2016 and 12.3% in 2019. Forty-six of these isolates were associated with the international clonal lineage IC2 and five with IC1. The most prevalent carbapenemase gene detected was blaOXA-23-like (n = 51). Further carbapenem-resistance determinants were blaOXA-40-like (n = 1), blaOXA-58-like (n = 3) and blaNDM-1 (n = 2). In one isolate, ISAba1 was detected upstream of blaOXA-51-like. In conclusion, IC2 was the most prevalent clonal lineage detected in this study. Interestingly, in Germany, carbapenem resistance seems to have decreased in A. baumannii between 2013 and 2019.(c) 2022 Published by Elsevier Ltd