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


Our latest research was just published in the prestigious journal Clinical Microbiology and Infection (European Society of Clinical Microbiology and Infectious Diseases), September 02, 2023.

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


Stamatis Karakonstantis, Maria Rousaki, Loukia Vassilopoulou, and Evangelos I. Kritsotakis

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Cefiderocol is a last resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially metallo-β-lactamase (MBL)-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.

Data sources

PubMed and Scopus, up to May 2023.

Study eligibility criteria

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 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, co-resistance phenotype and breakpoint definition (EUCAST, CLSI, 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 NDM-producing Enterobacterales (38.8%, 95%CI 22.6-58.0%), NDM-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.

Key words

carbapenem-resistant, Cefiderocol, drug resistance, global epidemiology, gram-negative bacteria, prevalence.

Figure. Summary forest plot of cefiderocol non-susceptibility against Enterobacterales

S is the number of independent sets of data in the analysis. n / N is the ratio of the cumulative number of isolates that were non-susceptible to cefiderocol (CFDC-NS) over the total number of isolates, according to the respective definition of breakpoints and resistance phenotype. The centre of the diamond is the population-averaged (pooled estimate) prevalence of CFDC-NS isolates. The length of the diamond indicates the 95% confidence interval (CI) for the pooled estimate. The horizontal thick lines extending from the diamond represent the 95% prediction interval (PI) for the prevalence of CFDCN-S isolates in new studies. 

CAR, carbapenem; MBL, metallo-β-lactamase; NDM, New Delhi metallo-β-lactamase; CZA, ceftazidime/avibactam; CTA, ceftolozane/tazobactam

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