Activity and Efficacy of Cefiderocol against Stenotrophomonas maltophilia.

Cefiderocol is a novel siderophore cephalosporin antibiotic with broad coverage against difficult-to-treat Gram-negative bacteria, including those resistant to carbapenems. Its activity against was investigated against clinical isolates and in lung infection models using strains either resistant (SR202006) or susceptible (SR201934, SR200614) to trimethoprim-sulfamethoxazole. Cefiderocol demonstrated potent activity against all 217 clinical isolates tested (MIC, 0.063 μg/ml; MIC, 0.25 μg/ml). Cefiderocol also demonstrated low MICs against the trimethoprim-sulfamethoxazole-resistant strains (i.e., SR202006; MIC, 0.125 μg/ml). In a neutropenic mouse lung infection model, cefiderocol (30 mg/kg body weight and 100 mg/kg) demonstrated a significant, dose-dependent reduction in the lung viable bacteria cell count compared with untreated controls in infection and was the only antibiotic tested to show a similar significant effect in a trimethoprim-sulfamethoxazole-resistant infection. In immunocompetent rat lung infection models of , humanized dosing of cefiderocol (2 g every 8 h) and meropenem (1 g every 8 h) revealed pharmacokinetic profiles similar to those in human subjects, and the humanized cefiderocol dosing significantly reduced the lung viable bacteria cell count compared with baseline controls, which received no intervention. Together, the results from these studies suggest that cefiderocol could provide an effective alternative treatment option for infections in the lower respiratory tract, particularly strains resistant to empirical antibiotics, such as trimethoprim-sulfamethoxazole or minocycline.