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Plazomicin (PLZ), brand name ZEMDRI (Cipla Therapeutics), is a novel aminoglycoside antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections including pyelonephritis. ETEST® is a gradient diffusion method that represents an alternative to the more laborious broth micro-dilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multi-center evaluation of the performance of the new ETEST PLZ (bioMérieux) was conducted in comparison with BMD following FDA and International Standards Organization (ISO) recommendations using FDA-defined breakpoints. Clinical isolates of Enterobacterales ( n  = 598) were included. Fifty-three isolates were resistant to PLZ according to BMD. Overall, the ETEST PLZ demonstrated 99.0% essential agreement (EA), 92.8% category agreement (CA), 1.9% very major errors (VME), 0% major errors (ME), and 7.0% minor errors (mE) with both clinical and challenge isolates of Enterobacterales. The VME was found for a single Serratia marcescens strain. Individual species demonstrated EA rates ≥ 90%. In conclusion, we report that ETEST PLZ represents an accurate tool for performing PLZ AST of Enterobacterales.

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.

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% (MIC 50/90 ) 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. MIC 50/90 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. MIC 50/90 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., (Copyright © 2020. Published by Elsevier Ltd.)

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 carbapenem-susceptible 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 CTT-susceptible. 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 carbapenem-resistant, 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., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

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 MIC 50/90 values of 0.25/0.5 mg/L and 0.25/1 mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and meropenem MIC 50/90 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 MIC 50/90 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., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Ceftobiprole is an investigational intravenous broad-spectrum cephalosporin with in vitro activity against Gram-positive and Gram-negative pathogens, including meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Pseudomonas aeruginosa is a frequent nosocomial pathogen, increasingly associated with complicated skin and skin-structure infections. Combination antimicrobial therapy is recommended as empirical therapy for serious infections where P. aeruginosa is suspected. Therefore, in this study the interaction of ceftobiprole with two other antipseudomonal agents (amikacin and levofloxacin) was investigated. Time-kill studies were performed for each single agent and for the combination of ceftobiprole 4 mg/L with either amikacin or levofloxacin at 0.5×, 1× and 2× the minimum inhibitory concentration. Five clinical isolates of P. aeruginosa as well as the P. aeruginosa ATCC 27853 reference strain were tested at initial inocula of 5×10(5) colony-forming units (CFU)/mL (low inoculum) or 5×10(7) CFU/mL (high inoculum). Synergy was defined as a decrease of ≥2log(10) CFU/mL with the combination compared with the most active single drug at 6 h and 24 h. At low inoculum with ceftobiprole as a single agent, viable counts were decreased by 1.5-2log(10) at 6 h. Addition of either amikacin or levofloxacin resulted in synergistic bactericidal activity at 24 h. At high inoculum the combination of ceftobiprole with amikacin or levofloxacin demonstrated synergism in one of three and three of five strains, respectively. This study demonstrated that the combination of ceftobiprole at a clinically achievable concentration of 4 mg/L with amikacin or levofloxacin exhibited synergistic activity against P. aeruginosa. There was no evidence of antagonism for either combination., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Antimicrobial resistance poses a global threat to public health. Of great concern are Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales with resistance to carbapenems or third-generation cephalosporins. The aim of the present study was to investigate the in vitro activity of the novel siderophore cephaloporin cefiderocol (CID) and four comparator β-lactam-β-lactamase-inhibitor combinations and to give insights into the genetic background of CID-resistant isolates. In total, 301 clinical Enterobacterales and non-fermenting bacterial isolates were selected for this study, including randomly chosen isolates (set I, n = 195) and challenge isolates (set II, n = 106; enriched with ESBL and carbapenemase producers, as well as colistin-resistant isolates). Isolates displayed CID MIC50/90 values of 0.12/0.5 mg/L (set I) and 0.5/1 mg/L (set II). Overall, the CID activity was superior to the comparators against A. baumannii, Stenotrophomonas maltophilia and set II isolates of P. aeruginosa. There were eight CID-resistant isolates detected (MIC > 2 mg/L): A. baumannii (n = 1), E. cloacae complex (n = 5) and P. aeruginosa (n = 2). Sequencing analyses of these isolates detected the acquired β-lactamase (bla) genes blaNDM-1, blaSHV-12 and naturally occurring blaOXA-396, blaACT-type and blaCMH-3. In conclusion, CID revealed potent activity against clinically relevant organisms of multidrug-resistant Enterobacterales and non-fermenters. [ABSTRACT FROM AUTHOR]

This cross-sectional in-vitro resistance surveillance study involving 10 medical laboratories was conducted in 2018. Each study site was asked to collect 30 consecutive nonduplicate isolates per species from hospitalized patients with documented infections. Minimum inhibitory concentrations were determined at a central laboratory. European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used for interpretation. A total of 860 isolates were collected, including 298 Escherichia coli, 268 Klebsiella pneumoniae, and 294 Pseudomonas aeruginosa. Fifty (16.8%) E. coli and 63 (23.5%) K. pneumoniae isolates were found to be resistant to third-generation cephalosporins. Resistance to carbapenems (imipenem and/or meropenem) was identified in 5 (1.9%) K. pneumoniae and 64 (21.8%) P. aeruginosa, but not in E. coli. Thirty-three (11.2%) P. aeruginosa isolates were resistant to both carbapenems and 30 (10.2%) P. aeruginosa showed resistance to ≥3 antimicrobials/antimicrobial groups (among piperacillin–tazobactam, ceftazidime, tobramycin, carbapenems, and fluoroquinolones). The susceptibility rates of these multidrug-resistant (MDR) phenotypes to ceftolozane–tazobactam, ceftazidime–avibactam, and imipenem–relebactam were 70–100%, with the exception of carbapenem-resistant K. pneumoniae. Only two K. pneumoniae and four P. aeruginosa isolates were resistant to all three beta-lactam/beta-lactamase-inhibitor combinations. However, this favorable result should be viewed in light of the relatively low prevalence of MDR organisms that require these agents in Germany. [ABSTRACT FROM AUTHOR]