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Will ceftazidime/avibactam plus aztreonam be effective for NDM and OXA-48-Like producing organisms: Lessons learnt

Agila Kumari Pragasam1, Balaji Veeraraghavan1, Baby Abirami Shankar1

  • 1Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.

Indian Journal of Medical Microbiology
|August 20, 2019
PubMed
Abstract

Insights

The combination of ceftazidime/avibactam (C/A) plus aztreonam (ATM) shows synergistic activity against carbapenem-resistant Klebsiella pneumoniae (CRKp) producing NDM and OXA-48 carbapenemases. This combination therapy is promising for treating difficult-to-treat CRKp infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Carbapenem resistance (CR) in Klebsiella pneumoniae is a growing global health threat, primarily driven by carbapenemases like NDM and OXA-48.
  • Ceftazidime/avibactam (C/A) is effective against OXA-48-like carbapenemase producers but less so against NDM co-producers.
  • Aztreonam (ATM) addition to C/A may broaden its activity against carbapenemase co-producers.

Purpose of the Study:

  • To evaluate the synergistic antimicrobial activity of ceftazidime/avibactam (C/A) in combination with aztreonam (ATM).
  • To assess this combination against Klebsiella pneumoniae isolates harboring bla NDM, bla OXA-48-like, or both carbapenemase genes.

Main Methods:

  • Minimum inhibitory concentrations (MICs) of C/A and ATM were determined for 12 carbapenem-resistant Klebsiella pneumoniae (CRKp) isolates.
  • A checkerboard assay was employed to evaluate the synergistic effects of the C/A plus ATM combination.
  • Fold differences in C/A MIC with and without ATM were calculated to infer synergy.

Main Results:

  • Ceftazidime/avibactam (C/A) monotherapy showed high MICs (>8 μg/ml) for most CRKp isolates.
  • Addition of aztreonam (ATM) at 4 μg/ml resulted in a >8-fold reduction in C/A MIC across all tested CRKp, indicating synergistic activity.
  • This synergistic effect was observed for isolates with bla NDM, bla OXA-48-like, and co-producing bla NDM + bla OXA-48-like genes, including colistin-resistant strains.

Conclusions:

  • The combination of ceftazidime/avibactam (C/A) plus aztreonam (ATM) demonstrates significant synergistic activity against carbapenem-resistant Klebsiella pneumoniae (CRKp).
  • This combination is a promising therapeutic strategy for CRKp infections mediated by NDM, OXA-48-like, and co-producing carbapenemases.
  • The findings support the potential clinical utility of C/A plus ATM for challenging CRKp infections.
Keywords:
AztreonamKlebsiella pneumoniaebla NDMbla OXA-48-likeceftazidime/avibactam

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