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Published on: November 16, 2016
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.
Background:
CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that β-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS.
Objectives:
We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype.
Methods:
Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS.
Results:
The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was ≤2 mg/L for 30% of isolates and 75% had an MIC of ≤8 mg/L (MIC90 = 16 mg/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all ≥32 mg/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone.
Conclusions:
CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.
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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