treat NDM 1 bacteria with aztreonam and ceftazidime avibactam

NDM-1 is an enzyme that hydrolyzes almost all β-lactams, with the exception of monobactams, such as aztreonam. The enzyme is encoded on a transmissible genetic element and therefore easily spread via horizontal transfer. NDM-1 was initially identified in 2009 in a K pneumoniae isolate resistant to all drugs except colistin. Since then, it has been identified predominantly in Enterobacterales and less commonly in Pseudomonas and Acinetobacter species. At present, there are limited therapies for NDM-1-producing isolates aside from colistin or tigecycline, both of which have unfavorable side effect profiles.

Clinical studies suggest that combination of aztreonam and ceftazidime-avibactam provides synergy, potentially because avibactam provides protection against hydrolysis of aztreonam, allowing aztreonam to inhibit cell wall synthesis. Several small studies have demonstrated that this synergistic combination can lead to successful treatment of infections caused by NDM-1-producing K pneumoniae. An observational study of 102 adults with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales reported that 30-day mortality was 19% for the ceftazidime-avibactam plus aztreonam group and 44% for the alternative arm. The 2023 published guidance from the Infectious Diseases Society of America recommends ceftazidime-avibactam plus aztreonam as a treatment option for NDM-1-producing bacteria. Critical care clinicians should be aware of this therapeutic option because of the limited alternative agents and the high mortality associated with inappropriate treatment of drug-resistant organisms.

NDM-1 enzymes hydrolyze β-lactams including ampicillin and cefepime, rendering these antibiotics ineffective in the treatment of carbapenemase-producing bacteria. Sulfamethoxazole-trimethoprim is not a recommended therapy for NDM-1-producing K pneumoniae.123456

Footnotes

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  2. Falcone M, Daikos GL, Tiseo G, et al. Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales. Clin Infect Dis. 2021;72(11):1871-1878. PubMed ↩

  3. Marshall S, Hujer AM, Rojas LJ, et al. Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae? Antimicrob Agents Chemother. 2017;61(4):e02243-16. PubMed ↩

  4. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections. Clin Infect Dis. Published online July 18, 2023. PubMed ↩

  5. Wenzler E, Deraedt MF, Harrington AT, et al. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. Diagn Microbiol Infect Dis. 2017;88(4):352-354. PubMed ↩

  6. Yasmin M, Fouts DE, Jacobs MR, et al. Monitoring ceftazidime-avibactam and aztreonam concentrations in the treatment of a bloodstream infection caused by a multidrug-resistant Enterobacter sp. carrying both Klebsiella pneumoniae carbapenemase-4 and New Delhi metallo-β-lactamase-1. Clin Infect Dis. 2020;71(4):1095-1098. PubMed ↩