Search

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.

Pseudomonas aeruginosa remains a prominent nosocomial pathogen. Detection of carbapenemase-producing P. aeruginosa is vital to dictate antimicrobial therapy and infection control measures. A pragmatic, minimum inhibitory concentration-based algorithm using imipenem AND meropenem-resistant plus ceftazidime-, cefepime-, and piperacillin/tazobactam-nonsusceptible criterion was derived to guide carbapenemase testing in P. aeruginosa. This study was an assessment of the algorithm's test performance in a cohort of 985 nonduplicate P. aeruginosa isolates collected from 20 German medical laboratories. Susceptibility data were assessed in the algorithm using both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretations. Sensitivity and specificity were calculated to evaluate algorithm test performance. The original algorithm criteria resulted in high specificity (95-97%) using both CLSI and EUCAST criteria; however, it failed to capture five carbapenemase-harboring isolates testing piperacillin/tazobactam susceptibility (CLSI/EUCAST). Two carbapenemase-producing isolates were also meropenem susceptible per EUCAST. A modified algorithm utilizing imipenem OR meropenem-resistant plus ceftazidime and cefepime nonsusceptible, improved the sensitivity of the criteria without significantly compromising specificity (CLSI sensitivity/specificity: 96%/94% and EUCAST sensitivity/specificity: 96%/95%). Application of the modified algorithm criteria resulted in high sensitivity and specificity using both CLSI and EUCAST interpretations in a large cohort of clinical P. aeruginosa. Utilization of this algorithm can improve the efficiency of carbapenemase testing in the clinical laboratory.

Recent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analyse an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals. Multidrug resistance of the opportunistic pathogen Stenotrophomonas maltophilia is an increasing problem. Here, analyzing strains from 22 countries, the authors show that the S. maltophilia complex is divided into 23 monophyletic lineages and find evidence for intra-hospital transmission.

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.

Objectives: To evaluate the activity of the novel broad-spectrum serine beta-lactamase inhibitor durlobactam (ETX2514) combined with sulbactam against global isolates of carbapenem-resistant Acinetobacter baumannii with defined carbapenem resistance mechanisms compared with reference antimicrobials with known activity against Acinetobacter spp. Methods: The susceptibility of 246 carbapenem-resistant non-duplicate A. baumannii isolates to sulbactam/durlobactam, amikacin, colistin, imipenem/sulbactam/durlobactam, imipenem, meropenem, minocycline and sulbactam was tested using broth microdilution. Isolates were obtained from various body sites from patients in 37 countries and from six world regions between 2012 and 2016. Identification of carbapenem resistance mechanisms and assignment to A. baumannii clonal lineages was based onWGS. Results: Sulbactam/durlobactam showed excellent activity comparable to colistin but superior to amikacin, minocycline and sulbactam. The sulbactam/durlobactam MIC50/90 values were 1/4 and 2/4 mg/L and the colistin MIC50/90 values were 0.5 and 1 mg/L, respectively. Comparatively, amikacin, minocycline and sulbactam MIC50/90 values were 256/>= 512, 2/16 and 16/64 mg/L, respectively. Conclusions: Sulbactam/durlobactam had excellent in vitro potency against A. baumannii isolates, including those that were resistant to imipenem/meropenem, amikacin, minocycline and colistin, compared with other compounds. Sulbactam/durlobactamhas the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problempathogen.

Objectives: Cefiderocol (CID), also known as S-649266, a novel siderophore cephalosporin, possesses potent activity against multidrug-resistant aerobic Gram-negative bacteria (GNB). This study aimed to determine the in vitro activity of CID against two different sets of GNB: i) a random sample of 213 clinical isolates, including 17 extended-spectrum beta-lactamase (ESBL) producers, obtained from intensive care unit patients with nosocomial infections collected during a multicentre surveillance study (set I); and ii) a group of 59 challenge GNB producing various types of carbapenemases (CP; set II). Methods: Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1. Iron-depleted medium was used for testing CID. Results: CID inhibited 97.2% of set I isolates at the EUCAST susceptibility breakpoint of <= 2 mg/L. The concentrations of CID inhibiting 50% and 90% (MIC50/90) of the Enterobacterales isolates (n = 146) were 0.12/1.0 mg/L, with ESBL-positive isolates tending to exhibit higher MICs than ESBL-negative isolates to CID. MIC50/90 values of CID for isolates of the Acinetobacter baumannii group (n = 13) and Pseudomonas aeruginosa (n = 54) were 0.06/0.12 mg/L and 0.12/0.5 mg/L, respectively. Further, CID inhibited 88.1% of set II CP-producing isolates at <= 2 mg/L. All seven class D CP-producing Acinetobacter baumannii were inhibited at < 0.25 mg/L. MIC50/90 values for CP-producing Enterobacterales (n = 30) and Pseudomonas aeruginosa (n = 22) were 1/4 mg/L and 0.5/2 mg/L, respectively. Conclusion: CID showed potent activity against Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa, including CP-producing isolates. Overall, CID inhibited 259 of 272 (95.2%) GNB at <= 2 mg/L. (C) 2020 The Authors. Published by Elsevier Ltd.

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.