Work

A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria

Year: 2024

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CR-GNB) develop resistance to many antimicrobials. To effectively manage infections caused by these organisms, novel agents and/or combinations of antimicrobials are required. OBJECTIVES: Evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB. METHODS: PubMed, Web of Science, Embase and Scopus were searched. Study outcomes were quantified by counting the number of isolates exhibiting synergy, defined as a fractional inhibitory concentration index ≤ 0.5 for checkerboard and Etest, and a >2 log cfu/mL reduction for time-kill studies. The proportion of synergy was calculated as the ratio of isolates exhibiting synergy to the total number of isolates tested. These proportions were analysed using a random-effects model, following the Freeman-Tukey double-arcsine transformation. RESULTS: Forty-five in vitro studies were included. A total of 734 isolates were tested, and 69.3% of them were resistant to ceftazidime/avibactam. The combination of ceftazidime/avibactam with aztreonam showed a high synergy rate against carbapenem-resistant Klebsiella pneumoniae (effect size, ES = 0.91-0.98) and Escherichia coli (ES = 0.75-1.00). Ceftazidime/avibactam also demonstrated a high synergy rate (ES = 1) in time-kill studies when combined with azithromycin, fosfomycin and gentamicin against K. pneumoniae. Compared to ceftazidime/avibactam alone, a higher bactericidal rate was reported when ceftazidime/avibactam was combined with other antimicrobials against carbapenem-resistant K. pneumoniae (57% versus 31%) and E. coli (93% versus 0%). CONCLUSIONS: Ceftazidime/avibactam frequently demonstrates synergistic bactericidal activity when combined with various antimicrobials against CR-GNB in in vitro tests. Further pre-clinical and clinical studies are warranted to validate the utility of ceftazidime/avibactam-based combination regimens for CR-GNB infections.

Source: Journal of Antimicrobial Chemotherapy

DOI: 10.1093/jac/dkae451

Authors: Getnet M Assefa, Jason A Roberts, Abdullah T Aslan, Solomon A Mohammed, Fekade B Sime

Institutions: The University of Queensland, Wollo University, Université de Montpellier, Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Microbiology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,851