Treatment of Ceftazidime-Avibactam–Aztreonam-Resistant New Delhi Metallo-β-Lactamase-Producing Escherichia coli Bacteremia With Imipenem-Cilastatin-Relebactam Plus Aztreonam: A Two-Case Report.

Abstract

Background:
Bloodstream infection due to New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli poses a major therapeutic challenge because these isolates are frequently resistant to carbapenems and often co-produce serine β-lactamases that compromise Aztreonam activity. Although Ceftazidime- Avibactam plus Aztreonam is commonly used for metallo-β-lactamase-producing Enterobacterales, resistance to this combination is increasingly recognized. Clinical evidence for Imipenem-Cilastatin- Relebactam plus Aztreonam as salvage therapy remains limited. We report 2 cases of Ceftazidime- Avibactam–Aztreonam-resistant NDM-producing E. coli bacteremia in which microbiological clearance was achieved with this combination.
Case Report:
The first patient was a 59-year-old man with newly diagnosed FLT3-ITD- and NPM1-mutated acute myeloid leukemia who presented with suspected hematologic sepsis and was found to have carbapenem-resistant NDM-producing E. coli bacteremia. The isolate was resistant to Ceftazidime- Avibactam and Ceftazidime-Avibactam plus Aztreonam, with susceptibility retained only to Colistin and aminoglycosides. Persistent fever and inflammatory progression occurred despite Ceftazidime-Avibactam plus Aztreonam, Meropenem, and Colistin. After switching to Imipenem-Cilastatin- Relebactam plus Aztreonam with Colistin and Gentamicin, blood cultures cleared and inflammatory markers improved, although the patient later died from leukemia-related complications rather than
persistent bacteremia. The second patient was a 91-year-old woman with chronic obstructive pulmonary disease, Alzheimer disease, diabetes mellitus, and chronic kidney disease who developed respiratory failure requiring intensive care. Blood and respiratory cultures grew NDM- and CTX-Mproducing E. coli resistant to Ceftazidime-Avibactam and Ceftazidime-Avibactam plus Aztreonam.
Renally adjusted, prolonged simultaneous infusions of Imipenem-Cilastatin-Relebactam and Aztreonam were associated with rapid clinical improvement, negative follow-up blood cultures, procalcitonin decline, and eventual discharge to long-term care.
Conclusion:
Imipenem-Cilastatin-Relebactam plus Aztreonam may be a valuable salvage option for severe bacteremia caused by extensively drug-resistant, Ceftazidime-Avibactam–Aztreonam-resistant NDM-producing Escherichia coli. In both patients, this regimen was associated with microbiological clearance despite major host-related risk factors and extensive antimicrobial resistance. These cases support further evaluation of this regimen in difficult-to-treat metallo-β-lactamase-producing Enterobacterales infections.