%0 Meta-Analysis
%T Global prevalence of cefiderocol non-susceptibility in Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia: a systematic review and meta-analysis.
%A Karakonstantis S
%A Rousaki M
%A Vassilopoulou L
%A Kritsotakis EI
%J Clin Microbiol Infect
%V 30
%N 2
%D 2024 Feb 4
%M 37666449
%F 13.31
%R 10.1016/j.cmi.2023.08.029
%X <B>BACKGROUND: </B>Cefiderocol is a last resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially metallo-β-lactamase-producing Pseudomonas aeruginosa and CR Acinetobacter baumannii. Monitoring global levels of cefiderocol non-susceptibility (CFDC-NS) is important.<BR><B>OBJECTIVE: </B>To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens.<BR><B>METHODS: </B>PubMed and Scopus, up to May 2023.<BR><B>METHODS: </B>Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates.<BR><B>UNASSIGNED: </B>Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains.<BR><B>RESULTS: </B>Binomial-Normal mixed-effects models were applied to estimate CFDC-NS prevalence by species, coresistance phenotype, and breakpoint definition (EUCAST, CLSI, and FDA). Sources of heterogeneity were investigated by subgroup and meta-regression analyses.<BR><B>RESULTS: </B>In all, 78 studies reporting 82 035 clinical isolates were analysed (87% published between 2020 and 2023). CFDC-NS prevalence (EUCAST breakpoints) was low overall but varied by species (S. maltophilia 0.4% [95% CI 0.2-0.7%], Enterobacterales 3.0% [95% CI 1.5-6.0%], P. aeruginosa 1.4% [95% CI 0.5-4.0%]) and was highest for A. baumannii (8.8%, 95% CI 4.9-15.2%). CFDC-NS was much higher in CR Enterobacterales (12.4%, 95% CI 7.3-20.0%) and CR A. baumannii (13.2%, 95% CI 7.8-21.5%), but relatively low for CR P. aeruginosa (3.5%, 95% CI 1.6-7.8%). CFDC-NS was exceedingly high in New Delhi metallo-β-lactamase-producing Enterobacterales (38.8%, 95% CI 22.6-58.0%), New Delhi metallo-β-lactamase-producing A. baumannii (44.7%, 95% CI 34.5-55.4%), and ceftazidime/avibactam-resistant Enterobacterales (36.6%, 95% CI 22.7-53.1%). CFDC-NS varied considerably with breakpoint definition, predominantly among CR bacteria. Additional sources of heterogeneity were single-centre investigations and geographical regions.<BR><B>CONCLUSIONS: </B>CFDC-NS prevalence is low overall, but alarmingly high for specific CR phenotypes circulating in some institutions or regions. Continuous surveillance and updating of global CFDC-NS estimates are imperative while cefiderocol is increasingly introduced into clinical practice. The need to harmonize EUCAST and CLSI breakpoints was evident.