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This study assessed the in vitro antimicrobial activity of ceftazidime–avibactam (CAZ-AVI) and a panel of comparator agents, including aztreonam, cefepime, ceftazidime, meropenem, imipenem, colistin, piperacillin–tazobactam, and tigecycline against isolates of fluoroquinolone-resistant (FQ-R) Klebsiella pneumoniae collected in 2018 and 2019 from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines. Of all the K. pneumoniae isolates (n = 10,906), 44.1% (4,814/10,906) were FQ-R. Of these, 71.3% (3,432/4,814) were extended-spectrum β-lactamase (ESBL)-positive, and 10.4% (499/4,814) were CAZ-AVI-resistant. CAZ-AVI showed high susceptibility (>87%) against all the FQ-R K. pneumoniae isolates. However, metallo- β-lactamase-positive isolates showed low susceptibility (3.8%; 18/470) to CAZ-AVI. Among the different geographical regions, CAZ-AVI showed the highest activity against isolates collected from North America (98.2%, 216/220) and lowest against those collected from Asia Pacific (APAC) (81.7%; 882/1,079). Among comparator agents, carbapenems showed a relatively lower susceptibility (<71.5%), while only tigecycline and colistin were active (>85%) across all isolates. In conclusion, CAZ-AVI may be a potential treatment option for FQ-R K. pneumoniae isolates. However, increasing CAZ-AVI resistance among ESBL-positive and metallo-β-lactamase-positive isolates and in isolates from APAC warrants continuous surveillance. [ABSTRACT FROM AUTHOR]

The in vitro activities of ceftazidime-avibactam and comparator agents were analyzed against 14,330 isolates of Pseudomonas aeruginosa from 188 centers distributed globally (except North America) from 2012 (2014 for colistin) to 2016 as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Susceptibility testing used in-house prepared broth microdilution panels following CLSI guidelines. Multiplex PCR assays identified the presence of β-lactamases. Ceftazidime-avibactam (MIC 90 8 mg/L; 91.5% susceptibility) and colistin (N = 11,032; MIC 90 2 mg/L, 96.2%) were the 2 most active agents. Susceptibility of multidrug-resistant isolates (N = 3770, 26.3%) was ≤54.4% to all agents except colistin (N = 2956; 95.2% susceptible) and ceftazidime-avibactam (68.2%). Metallo-β-lactamase–positive isolates (N = 621, 4.3%) were not susceptible to any agents except colistin (N = 504; 98.2% susceptible). Novel therapeutic options are needed for infections caused by P. aeruginosa –resistant phenotypes. [ABSTRACT FROM AUTHOR]

Background Gepotidacin (GSK2140944) is a first in class novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study assessed the in vitro activity of gepotidacin and comparators against a collection of 649 Gram-positive and Gram-negative anaerobic bacterial clinical isolates. Methods A total of 649 clinically significant Gram-negative (333) and Gram-positive (316) anaerobic clinical isolates previously collected and frozen at −70°C were tested. Isolates came from North America (315/48.5%) and Europe (334/51.5%) and were collected between 2000 and 2017. Minimum inhibitory concentrations (MICs) for gepotidacin and 6 comparators were determined by agar dilution (AD) for all isolates, and by both AD and broth microdilution (BMD) for Bacteroides spp. according to CLSI guidelines (CLSI M11-A8). Most Lactobacillus spp. tested in this study require anaerobic conditions for growth and were tested by anaerobic AD. Results The in vitro activity results of gepotidacin and comparators are shown in the table below. The gepotidacin MIC90 for all Gram-negative anaerobic isolates tested in this study was 4 µg/mL and for the comparators tested was as follows: ceftriaxone 512 μg/mL, clindamycin >8 μg/mL, imipenem 0.5 μg/mL, metronidazole 2 μg/mL, moxifloxacin 8 μg/mL and piperacillin–tazobactam 16 μg/mL. Gepotidacin had the lowest MIC90 (2 μg/mL) for the Gram-positive anaerobic isolates compared with the other antibiotics tested, with the exception of metronidazole (MIC90 = 0.5 µg/mL). Conclusion Gepotidacin showed in vitro activity against a collection of 649 anaerobic Gram-negative and Gram-positive clinical isolates, with an MIC90 value against all Gram-negative anaerobic isolates of 4 µg/mL, and against all Gram-positive anaerobic isolates of 2 µg/mL. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]