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Multidrug-resistant Acinetobacter baumannii strains with NDM-1: Molecular characterization and in vitro efficacy of

Jingjing Wang1, Yongzhong Ning2, Shu Li3

  • 1Department of Laboratory Medicine, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471000, P.R. China.

Experimental and Therapeutic Medicine
|October 2, 2019
PubMed

Insights

Combination therapies show promise against multidrug-resistant Acinetobacter baumannii. Meropenem combined with vancomycin, tazobactam, ampicillin-sulbactam, or colistin demonstrated synergistic effects, offering new treatment options for NDM-1 positive infections.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Acinetobacter baumannii is a major cause of hospital-acquired, multidrug-resistant (MDR) infections globally.
  • Combination antimicrobial regimens are often the only viable treatment for MDR A. baumannii infections.
  • The New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme confers resistance to carbapenems, a critical class of antibiotics.

Purpose of the Study:

  • To evaluate the efficacy of meropenem combined with colistin, ampicillin-sulbactam, tazobactam, and vancomycin against clinical MDR A. baumannii strains.
  • To characterize antimicrobial resistance genes and the genetic background of NDM-1 in these strains.
  • To identify synergistic drug effects in combination therapies.

Main Methods:

  • Antimicrobial susceptibility testing was performed.
  • Resistance genes were identified using multiplex PCR-reverse line blot assay.
  • NDM-1 presence and genetic background were analyzed using primer walking, modified Hodge test, and EDTA-combined disk test.
  • Synergistic effects were screened using checkerboard assays to calculate the fractional inhibitory concentration index.

Main Results:

  • Five MDR A. baumannii strains carrying multiple resistance genes were identified.
  • Synergistic effects were observed for meropenem + vancomycin, meropenem + tazobactam, and meropenem + ampicillin + sulbactam (in two strains each), and meropenem + colistin (in four strains).
  • The NDM-1 gene was found integrated in a transposon structure with the ISAba125 insertion sequence, though genetic backgrounds varied.

Conclusions:

  • Meropenem-based combination therapies, particularly with colistin, vancomycin, tazobactam, and ampicillin-sulbactam, show synergistic activity against MDR A. baumannii strains.
  • The genetic variability of NDM-1, often associated with ISAba125, may contribute to its rapid dissemination.
  • Meropenem may enhance the efficacy of other antibiotics in NDM-1-positive MDR A. baumannii infections.
Keywords:
Acinetobacter baumanniiNew Delhi metallo-β-lactamase 1antimicrobial effectmetallo-β-lactamasemultidrug-resistant

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