Treatment of invasive IMP‐4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review

• Published in: Transplant infectious disease Vol. 23; no. 2; pp. e13510 - n/a
• Main Authors: Cairns, Kelly A., Hall, Victoria, Martin, Genevieve E., Griffin, David W.J., Stewart, James D., Khan, Sadid F., Abbott, Iain J., Meher‐Homji, Zaal, Morrissey, Catherine O., Sia, Christopher, Love, Jane, Corallo, Carmela E., Bergin, Peter, Sharma, Ashish, Basu, Gopal, Spencer, Andrew, Peleg, Anton Y.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01-04-2021
• Subjects: Anti-Bacterial Agents - therapeutic use; Antiinfectives and antibacterials; Antimicrobial agents; antimicrobial resistance; antimicrobials; Azabicyclo Compounds - therapeutic use; Aztreonam; Aztreonam - therapeutic use; Bacterial Proteins; beta-Lactamases; Carbapenemase; Ceftazidime; Ceftazidime - therapeutic use; Drug Combinations; E. cloacae; Enterobacter cloacae; Enterobacteriaceae Infections - drug therapy; Gram-negative bacteria; Humans; Infections; Klebsiella; Literature reviews; MBL; Metallo-β-lactamase; Metallography; metallo‐beta‐lactamase; Microbial Sensitivity Tests; Stem cells; Toxicity; Transplant Recipients; antimicrobials; antimicrobial resistance; MBL; metallo-beta-lactamase; E. cloacae
• ISSN: 1398-2273; 1399-3062
• DOI: 10.1111/tid.13510

Infections caused by carbapenemase‐producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo‐β‐lactamase (MBL)‐producing Gram‐negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer β‐lactamase inhibitors such as avibactam have well‐established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL‐producing organisms. Conversely, aztreonam has activity against MBL‐producing organisms but is often inactivated by other co‐existing β‐lactamases. Here, we report four cases of invasive MBL‐CPE infections in transplant recipients caused by IMP‐4‐producing Enterobacter cloacae who were successfully treated with a new, mechanism‐driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high‐risk patients with CPE infection, with reduced drug interactions and toxicity.