What question did this study set out to answer?

To investigate high-level cefiderocol resistance in NDM-producing Klebsiella pneumoniae infections.

January 14, 2026Open Access

P-1197. NDM-5 and Siderophore Receptor Mutations Drive High Level Cefiderocol Resistance in Klebsiella pneumoniae: A Case Series

MPMichelle Potter WAWajih AskarBanner - University Medical Center Phoenix GGGerardo F Gomez-AbundisBanner - University Medical Center Phoenix

Key Points

To investigate high-level cefiderocol resistance in NDM-producing Klebsiella pneumoniae infections.
Case series involving 12 patients with cefiderocol-resistant NDM-producing K. pneumoniae infections from January 2023 to July 2024.
Whole genome sequencing was performed to analyze resistance mechanisms and mutations in siderophore transporters and porins.
Outcomes included monitoring for microbiologic recurrence and treatment efficacy.
Cefiderocol resistance was observed despite some patients lacking prior exposure.
NDM-5 was identified in all analyzed isolates, along with additional mutations linked to resistance.
Treatment with ceftazidime/avibactam plus aztreonam was effective for most, although recurrence occurred.

Abstract

Abstract Background Infections with Carbapenem-resistant Enterobacterales (CREs) are a serious public health threat. The emergence of distinct New Delhi metallo-beta-lactamase (NDM)-producing K. pneumoniae strains resistant to cefiderocol is a significant concern given the limited armamentarium for these carbapenemases.Table 1:Baseline CharacteristicsCNS = central nervous system, LTCF = long-term care facilities, MIC = minimum inhibitory concentration, NDM = New Delhi metallo-beta-lactamase, OSH = outside hospital, SSTI = skin and soft tissue infection, UTI = urinary tract infectionTable 2:Outcomes1Patient was switched from tigecycline to ceftazidime/avibactam + aztreonam due to breakthrough bacteremia with the same NDM K. pneumoniae2Patient was switched from ceftazidime/avibactam + aztreonam to meropenem/vaborbactam + aztreonam due to polymicrobial infection with an E. coli that was resistant to ceftazidime/avibactam but susceptible to meropenem/vaborbactam3Recurrence was treated with ceftazidime/avibactam + aztreonam for 7 days Methods A case series of 12 patients was described from a single institution that had cefiderocol-resistant, NDM-producing K. pneumoniae infections between January 2023 and July 2024. Whole genome sequencing was performed to analyze resistance mechanisms, as well as mutations in siderophore transporters and porins.Whole Genome Sequencing Results Results Patients presented with various infections, including skin and soft tissue infections, pneumonia, and bacteremia. Of concern, cefiderocol resistance was seen among patients with and without prior cefiderocol exposure. Genomic analysis for 9 patients revealed NDM-5 in every isolate, along with additional mutations associated with resistance. Treatment with ceftazidime-avibactam plus aztreonam was successful in most instances, although microbiologic recurrence occurred in certain cases. Conclusion High level cefiderocol-resistance among NDM-5 producing K. pneumoniae with siderophore mutations add more challenges to treating CRE infections. Stricter infection control measures along with enhanced surveillance are needed, especially in regions where NDM is endemic to limit additional spread of these variants. Disclosures Emir Kobic, BCIDP, Shionogi: Honoraria

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Cite This Study

Potter et al. (Thu,) studied this question.

synapsesocial.com/papers/6966f30613bf7a6f02c00849 https://doi.org/https://doi.org/10.1093/ofid/ofaf695.1390

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