Global prevalence of cefiderocol non-susceptibility in Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia: a systematic review and meta-analysis.

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. To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens. PubMed and Scopus, up to May 2023. Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates. Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains. 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. 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. 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.

Karakonstantis S ，Rousaki M ，Vassilopoulou L ，Kritsotakis EI ... -  《-》

In vitro activity of cefiderocol against carbapenemase-producing and meropenem-non-susceptible Gram-negative bacteria collected in the Japan Antimicrobial Resistant Bacterial Surveillance.

The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against these pathogens. Several studies have reported the in vitro activity of CFDC against isolates from Europe, the United States, and China, but the activity against carbapenem-resistant bacteria with IMP-type carbapenemase has not been extensively studied. We, therefore, studied the in vitro activities of CFDC against carbapenem-resistant bacteria with available genomic backgrounds based on whole-genome sequencing (WGS) in Japan, where the IMP-type is the predominant carbapenemase produced by Gram-negative rods. We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from a collection of Gram-negative clinical isolates collected during a Japan Antimicrobial Resistance Bacterial Surveillance program and evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-non-susceptible Enterobacterales, and carbapenemase-producing nonfermentative bacteria. Among these, 97.7% of carbapenemase-producing Enterobacterales (99.2% of IMP-type carbapenemase-producing Enterobacterales), 100% of carbapenemase-producing P. aeruginosa, and 91.2% of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. CFDC was highly effective against class A-, B-, and D β-lactamase-harbouring isolates when compared to the other antimicrobial agents. In addition, the relationship between CFDC resistance and three genetic factors involved in resistance was discussed. This is the first large-scale study to systematically demonstrate the efficacy of CFDC against IMP-type carbapenemase-producing strains with known genomic backgrounds.

Kayama S ，Kawakami S ，Kondo K ，Kitamura N ，Yu L ，Hayashi W ，Yahara K ，Sugawara Y ，Sugai M ... -  《-》

Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.

Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used. Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125-8 mg/L and 0.5-8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of >4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of <4 mg/L, including those resistant to ceftolozane/tazobactam. S. maltophilia isolates displayed cefiderocol MICs of <4 mg/L, including those resistant to levofloxacin and/or trimethoprim/sulfamethoxazole. Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection.

Delgado-Valverde M ，Conejo MDC ，Serrano L ，Fernández-Cuenca F ，Pascual Á ... -  《-》

In Vitro Activity of Cefiderocol against U.S. and European Gram-Negative Clinical Isolates Collected in 2020 as Part of the SENTRY Antimicrobial Surveillance Program.

Shortridge D ，Streit JM ，Mendes R ，Castanheira M ... -  《Microbiology Spectrum》

In Vitro Susceptibility of Gram-Negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies, 2014 to 2019.

Karlowsky JA ，Hackel MA ，Takemura M ，Yamano Y ，Echols R ，Sahm DF ... -  《-》