Presentation (CTI)

OBJECTIVES: We aimed to compare the efficacy and safety of cefiderocol against alternative antibiotics for multidrug-resistant Gram-negative complicated urinary tract infections (cUTI).
METHODS: A systematic review and feasibility assessment was conducted in 2019 and updated in November 2025 to identify RCTs comparing specified parenteral antibiotics for Gram-negative pathogens in cUTI. Evidence networks were constructed for clinical and safety outcomes including microbiological eradication (ME), clinical cure, combined ME/clinical cure, measured at test of cure (TOC) and sustained follow-up (SFU), and all-cause and drug-related adverse events (AEs). Outcomes were analysed using microbiological intention-to-treat and safety populations, respectively; Gram-negative subgroups were pooled where required. Analyses used a Bayesian hierarchical framework with Markov chain Monte Carlo simulation (fixed effects models).
RESULTS: 26 eligible studies were identified, of which 9 studies (comprising 9 interventions and 5,130 participants) contributed to networks with cefiderocol. Other interventions evaluated were levofloxacin, best available therapy (BAT), imipenem-cilastatin and combinations (n=3), ceftazidime-avibactam, ceftolozane-tazobactam and doripenem. Cefiderocol appeared to be more effective than other interventions for all efficacy outcomes, reaching statistical significance at TOC for ME (versus imipenem-cilastatin [relative risk: 0.72; 95% CrI: 0.63, 0.81]; doripenem [0.70; 0.50, 0.97], and BAT [0.60; 0.42, 0.85]) and combined ME/clinical cure (versus imipenem-cilastatin [0.70; 0.57, 0.83]). At SFU, significance was also observed against imipenem-cilastatin for ME (0.74; 0.57, 0.93), clinical cure (0.87; 0.80, 0.95), and combined ME/clinical cure (0.68; 0.54, 0.86). Cefiderocol had the highest SUCRA value for all efficacy outcomes. Safety profiles were comparable to cefiderocol; differences in drug-related AEs lacked statistical significance, whereas all-cause AEs reached significance (versus imipenem cilastatin [1.26; 1.01, 1.55]). Random-effects sensitivity analyses yielded similar central estimates but wider confidence intervals, losing statistical significance for some outcomes.
CONCLUSIONS: Cefiderocol performed favourably compared with comparators for all efficacy outcomes. However, safety results were mixed. Additional evidence may reduce the uncertainty in effect measures.