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

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-beta-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer beta-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 beta-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.

Automated summary

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) pose a emerging threat in transplant recipients, often resulting in high mortality due to limited treatment options and toxicities. A novel approach using a combination of ceftazidime/avibactam with aztreonam has shown promise in successfully treating invasive MBL-CPE infections, offering a new treatment option with reduced drug interactions and toxicity for high-risk patients.