In vitro activity of cefiderocol against multidrug-resistant Gram-negative bacteria and molecular characterization of carbapenem-resistant isolates in Niger

Abstract Background The emergence and spread of multidrug-resistant (MDR) Gram-negative bacteria represent a major public health threat worldwide, particularly in low- and middle-income countries where therapeutic options are limited. Cefiderocol is a novel siderophore cephalosporin with a unique mechanism of iron-dependent cellular uptake that enables it to overcome many common resistance mechanisms, including carbapenemases. However, data on its in vitro activity against MDR isolates from West Africa remain scarce. This study aimed to evaluate the in vitro activity of cefiderocol against a collection of MDR Gram-negative bacilli isolated in Niger and to characterize the underlying carbapenemase genes. Methods A total of 464 non-duplicate MDR Gram-negative clinical isolates were retrospectively collected between November 2024 and July 2025 from the National Reference Laboratory for Antimicrobial Resistance Surveillance in Niger. The collection comprised extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E, n = 329), carbapenem-resistant Enterobacterales (CRE, n = 95), carbapenem-resistant Acinetobacter baumannii (CRAB, n = 18), and carbapenem-resistant Pseudomonas aeruginosa (CRPA, n = 22). Minimum inhibitory concentrations of cefiderocol were determined by E-test (0.016–256 mg/L) on Mueller-Hinton agar, and susceptibility was interpreted according to EUCAST 2024 breakpoints (susceptible ≤ 2 mg/L). The presence of carbapenemase genes ( bla KPC , bla NDM−1 , bla VIM , bla OXA−48-like ) was investigated by real-time PCR. Results Overall, 452 of 464 isolates (97.4%; 95% CI 95.5–98.7%) were susceptible. Susceptibility rates were 100% (329/329) among ESBL-E, 95.5% (21/22) among CRPA, 94.4% (17/18) among CRAB, and 89.5% (85/95) among CRE. Among the 135 carbapenem-resistant isolates, 33 (24.4%) carried at least one carbapenemase gene: bla NDM−1 (40.7%), bla VIM (39.0%), bla OXA−48-like (18.6%), and bla KPC (1.7%). Twelve isolates (2.6%) were resistant to cefiderocol (MIC > 2 mg/L). High-level resistance (MIC ≥ 64 mg/L) was observed in five isolates, four of which carried bla NDM−1 (alone or in combination). One Escherichia coli isolate with high-level resistance (MIC = 256 mg/L) carried no detectable carbapenemase gene, suggesting alternative mechanisms. Conclusions Cefiderocol shows potent in vitro activity against MDR Gram-negative bacilli from clinical specimens in Niger (97.4% susceptible). Resistance remains rare (2.6%) but is associated with NDM-1 producers and one isolate without detected carbapenemase genes. These findings support cefiderocol as a potential last-line option, while emphasising the urgent need for routine susceptibility testing, active surveillance, and antimicrobial stewardship in West Africa.