Outcomes of 23 patients diagnosed with New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae infection treated with ceftazidime/avibactam and aztreonam at a single center in Poland

Eur J Clin Microbiol Infect Dis. 2024 Aug;43(8):1579-1587. doi: 10.1007/s10096-024-04859-y. Epub 2024 May 29.

Abstract

Purpose: Amongst all etiologic hospital-acquired infection factors, K. pneumoniae strains producing New Delhi metallo-β-lactamase (KP-NDM) belong to pathogens with the most effective antibiotic resistance mechanisms. Clinical guidelines recommend using ceftazidime/avibactam with aztreonam (CZA + AT) as the preferred option for NDM-producing Enterobacterales. However, the number of observations on such treatment regimen is limited. This retrospective study reports the clinical and microbiological outcomes of 23 patients with KP-NDM hospital-acquired infection treated with CZA + AT at a single center in Poland.

Methods: The isolates were derived from the urine, lungs, blood, peritoneal cavity, wounds, and peritonsillar abscess. In microbiological analysis, mass spectrometry for pathogen identification, polymerase chain reaction, or an immunochromatographic assay for detection of carbapenemase, as well as VITEK-2 system, broth microdilution, and microdilution in agar method for antimicrobial susceptibility tests were used, depending of the pathogens' nature. CZA was administered intravenously (IV) at 2.5 g every eight hours in patients with normal kidney function, and aztreonam was administered at 2 g every eight hours IV. Such dosage was modified when renal function was reduced.

Results: KP-NDM was eradicated in all cases. Four patients (17.4%) died: three of them had a neoplastic disease, and one - a COVID-19 infection.

Conclusion: The combination of CZA + AT is a safe and effective therapy for infections caused by KP-NDM, both at the clinical and microbiological levels. The synergistic action of all compounds resulted in a good agreement between the clinical efficacy of CZA + AT and the results of in vitro susceptibility testing.

Keywords: Avibactam, Ceftazidime drug combination; Aztreonam; Beta-lactamases; Klebsiella pneumoniae.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Azabicyclo Compounds* / pharmacology
  • Azabicyclo Compounds* / therapeutic use
  • Aztreonam* / pharmacology
  • Aztreonam* / therapeutic use
  • Ceftazidime* / pharmacology
  • Ceftazidime* / therapeutic use
  • Cross Infection / drug therapy
  • Cross Infection / microbiology
  • Drug Combinations*
  • Female
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae* / drug effects
  • Klebsiella pneumoniae* / enzymology
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Poland
  • Retrospective Studies
  • Treatment Outcome
  • beta-Lactamases* / metabolism

Substances

  • Aztreonam
  • beta-Lactamases
  • Azabicyclo Compounds
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime
  • Anti-Bacterial Agents
  • beta-lactamase NDM-1