NDM‑mediated cefiderocol resistance among a series of carbapenem‑resistant Gram‑negative bacilli isolates in Niger

Background The emergence of cefiderocol resistance, particularly among NDM-producing Gram-negative bacilli, threatens the utility of this last-line antibiotic; however, data from West Africa remain scarce. Methods This case series characterized 12 cefiderocol-resistant, carbapenem-resistant Gram-negative bacilli clinical isolates collected in Niger between November 2024 and July 2025. Species identification and antimicrobial susceptibility testing were performed using VITEK® 2 Compact and Etest on iron-depleted Mueller-Hinton agar. Carbapenemase genes ( bla KPC , bla NDM-1 , bla VIM , bla OXA-48-like ) were detected by real-time PCR. Results Escherichia coli was the predominant species (7/12, 58.3%). Carbapenemase genes were detected in six isolates (50.0%), with bla NDM-1 present in five isolates (41.7%), either alone (n = 2) or in combination with bla VIM and bla OXA-48-like (n = 2); one Acinetobacter baumannii isolate co-harboured bla KPC , bla VIM , bla NDM-1 and bla OXA-48-like . NDM-positive isolates exhibited a higher median cefiderocol MIC (256 mg/L, range 3–256) compared to NDM-negative isolates (4 mg/L, range 3–256), but this difference was not statistically significant (Wilcoxon rank-sum test, p = 0.33). Ceftazidime-avibactam resistance was universal among NDM-positive isolates (5/5, 100%) but was also frequent among NDM-negative isolates (4/7, 57.1%). No significant differences were observed between NDM-positive and NDM-negative isolates for any of the non-β-lactam antibiotics tested (Fisher’s exact test, all p > 0.05). Notably, six isolates (50.0%) had no detectable carbapenemase genes, suggesting that alternative, non-enzymatic resistance mechanisms such as siderophore receptor alterations, iron-uptake system modifications, or porin deficiencies may play a substantial role in this setting. Conclusion Cefiderocol resistance among carbapenem-resistant Gram-negative bacilli in Niger is a multifaceted phenomenon involving both NDM-mediated and non-enzymatic pathways. The lack of a statistically significant association between NDM carriage and MIC elevation, together with the high prevalence of isolates without detectable carbapenemase genes, underscores the urgent need for enhanced phenotypic susceptibility testing, broader molecular surveillance, and antimicrobial stewardship to preserve the efficacy of this last-line antibiotic in West Africa.