Rising threats of ceftolozane-tazobactam resistance in P. aeruginosa and A. baumannii: Species-, phenotype-, and geography-specific insights from a systematic review and meta-analysis.

BACKGROUND

Ceftolozane-tazobactam (C/T) is increasingly used to treat multidrug-resistant Gram-negative infections, but rising resistance threatens its effectiveness. Understanding global patterns is essential for guiding therapy and stewardship.

METHODS

We conducted a systematic review and meta-analysis of studies reporting C/T resistance in Pseudomonas aeruginosa and Acinetobacter baumannii. Pooled resistance proportions were estimated using random-effects models, with subgroup analyses by species, resistance phenotype, infection source, geography, and study period. Heterogeneity, temporal trends, and potential biases were assessed.

RESULTS

Among 75,403 tested isolates, 14,379 were resistant, yielding an overall pooled C/T resistance estimate of 26.2%. P. aeruginosa showed moderate resistance (12.6%), rising sharply in MDR (21.8%) and XDR (44.4%) subsets. A. baumannii demonstrated near-universal resistance (88.2%), particularly among carbapenem-resistant strains (≈99%). Resistance increased over time, from 19.9% in 2013-2021 to 38.7% in 2022-2024. Geographic differences were notable: high prevalence in Germany (46.6%), Mexico (42.6%), and Egypt (41.3%), and lower rates in Taiwan (15.1%) and Canada (1.7%). Respiratory isolates exhibited the highest resistance (49.4%), whereas bloodstream and pediatric infections were lower, though data were limited. Subgroup analyses for XDR, PDR, and carbapenemase producers were constrained by small study numbers.

CONCLUSIONS

C/T retains activity against many P. aeruginosa isolates but is increasingly compromised in MDR/XDR and carbapenemase-producing strains. A. baumannii shows consistently high resistance, limiting C/T utility. Rapidly rising resistance, infection-site variability, and geographic heterogeneity highlight the urgent need for targeted stewardship, local susceptibility-guided empiric therapy, and ongoing research into alternative or combination therapies.