Cefazolin susceptibility of coagulase-negative staphylococci (CoNS) causing late-onset neonatal bacteraemia

I Marr1, K Swe2, A Henderson3

  • 1Infectious Disease Department, The Canberra Hospital, ACT, Australia.

Abstract

Insights

Cefazolin shows lower minimum inhibitory concentrations (MICs) against Coagulase-negative staphylococci (CoNS) in neonates compared to other beta-lactams. This suggests cefazolin may be a viable alternative for treating neonatal sepsis caused by these bacteria.

Area of Science:

  • Microbiology
  • Neonatal Medicine
  • Infectious Diseases

Background:

  • Coagulase-negative staphylococci (CoNS) bloodstream infections (bacteraemia) are a significant cause of morbidity in neonates.
  • Previous research indicates variability in beta-lactam antibiotic binding affinity to PBP2a, a protein produced by the mecA gene found in most CoNS.

Purpose of the Study:

  • To evaluate cefazolin's minimum inhibitory concentrations (MICs) for CoNS isolated from neonates in an Australian neonatal intensive care unit (NICU).
  • To correlate these MICs with the genotype and phenotype of the CoNS isolates.

Main Methods:

  • Significant blood isolates (2009-2017) were speciated and tested for susceptibility to cefazolin, cefoxitin, oxacillin, and flucloxacillin using broth microdilution.
  • Correlation with mecA gene presence and PBP2a expression was assessed.
  • Whole Genome Sequencing (WGS) was performed on a subset of Staphylococcus capitis isolates.

Main Results:

  • The study identified 99 CoNS isolates, predominantly Staphylococcus capitis (n=57) and Staphylococcus epidermidis (n=32).
  • Cefazolin exhibited lower MIC values (MIC90 = 16 mg/L) compared to cefoxitin, oxacillin, and flucloxacillin (all MIC90s ≥32 mg/L).
  • WGS revealed the presence of the globally established NRCS-A clone of S. capitis.

Conclusions:

  • CoNS isolates demonstrated notably lower MICs for cefazolin than for other tested agents.
  • Variations in cefazolin MICs may be attributed to PBP2a binding affinity or regulation of mecA expression.
  • The persistent presence of NRCS-A S. capitis strains warrants further investigation into potential common environmental sources and supports a randomized clinical trial comparing cefazolin and vancomycin for neonatal sepsis.

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