Cefiderocol Heteroresistance in NDM-Producing Enterobacterales: A Complex Polymicrobial Infection Successfully...

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Heteroresistance in New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) is an underrecognized cause of treatment failure.
• Cefiderocol is a key therapy for metallo-ß-lactamase-producing organisms, but real-time development of discordant susceptibility is rarely described.

Purpose of the Study:

• To present a case of site-specific cefiderocol heteroresistance in NDM-producing CRE.
• To highlight the diagnostic and therapeutic implications of divergent antimicrobial susceptibility within a single patient.

Main Methods:

• A case report detailing a patient with a complex prosthetic joint infection and subsequent disseminated NDM-producing CRE infection.
• Simultaneous susceptibility testing of isolates from different anatomical sites during empiric cefiderocol therapy.
• Advanced microbiologic evaluation to identify synergistic treatment options.

Main Results:

• Empiric cefiderocol therapy revealed discordant susceptibility, with respiratory isolates becoming resistant while wound isolates remained susceptible.
• Advanced testing identified synergy with ceftazidime-avibactam plus aztreonam.
• Patient clinical stabilization following amputation and transition to synergistic therapy.

Conclusions:

• This case demonstrates real-time cefiderocol heteroresistance with site-specific divergence in NDM-producing CRE.
• Emphasizes the limitations of single-site susceptibility testing and the need for repeat, multi-site evaluations.
• Highlights the importance of early recognition of heteroresistant subpopulations and timely escalation of therapy for complex multidrug-resistant infections.