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Cefazolin Inoculum Effect and Cefazolin Microbiological Treatment Failure in Serious Methicillin-Susceptible
Mitchell A Jeffs1, Nicole Li1, Oluwalade Ogunkoya1
1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Background:
It remains unclear if cefazolin inoculum effect (CzIE) translates to poorer clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections who were treated with cefazolin.
Methods:
This retrospective cohort study across 5 hospitals in Ontario, Canada, from 2021 to 2025 included adult patients who received cefazolin treatment for serious MSSA infection based on blood or deep sterile site culture growth. CzIE was defined as a ≥4-fold increase in cefazolin minimum inhibitory concentration to ≥16 μg/mL at a high inoculum based on broth microdilution assay. Patients were followed to 90 days. Primary outcome was all-cause mortality. Secondary outcome was microbiological treatment failure based on culture growth of MSSA after 1 week of cefazolin treatment. Potential confounders were adjusted using propensity score weighting, and a competing risk model for microbiological treatment failure was used to account for mortality as a competing event.
Results:
Of 259 patients, 92 (35.5%) patients had an MSSA isolate that displayed CzIE. The 90-day mortality rate was 19/92 (20.7%) and 37/167 (22.2%) in the CzIE-positive and -negative groups, respectively, with adjusted risk difference of 0.6% (95% CI, -9.0% to 10.2%; P = .9060). Microbiological treatment failure occurred in 19/92 (20.7%) and 10/167 (6.0%) from the CzIE-positive and -negative groups, respectively, with adjusted subdistribution hazard ratio of 3.12 (95% CI, 1.38-7.08; P = .0065) in a competing risk model.
Conclusions:
CzIE was associated with a significantly increased risk of microbiological treatment failure. CzIE testing may be useful in guiding antibiotic treatment for serious MSSA infections.
Insights
Cefazolin inoculum effect (CzIE) in methicillin-susceptible Staphylococcus aureus (MSSA) infections did not impact mortality but significantly increased microbiological treatment failure risk. CzIE testing may guide cefazolin therapy for serious MSSA infections.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Pharmacology
Background:
- The clinical significance of cefazolin inoculum effect (CzIE) in methicillin-susceptible Staphylococcus aureus (MSSA) infections treated with cefazolin remains uncertain.
- Investigating the link between CzIE and patient outcomes is crucial for optimizing antibiotic strategies.
Purpose of the Study:
- To determine if cefazolin inoculum effect (CzIE) in patients with serious MSSA infections correlates with clinical outcomes.
- To assess the association between CzIE and 90-day all-cause mortality and microbiological treatment failure.
Main Methods:
- Retrospective cohort study of 259 adult patients treated with cefazolin for serious MSSA infections across five Ontario hospitals (2021-2025).
- CzIE defined as a ≥4-fold increase in cefazolin MIC to ≥16 μg/mL at high inoculum via broth microdilution.
- Propensity score weighting and competing risk models were used to adjust for confounders and competing events (mortality).
Main Results:
- Of 259 patients, 92 (35.5%) had MSSA isolates exhibiting CzIE.
- No significant difference in 90-day all-cause mortality between CzIE-positive and CzIE-negative groups (adjusted risk difference 0.6%).
- Microbiological treatment failure was significantly higher in the CzIE-positive group (20.7% vs. 6.0%, adjusted sub-distribution hazard ratio 3.12, p=0.0065).
Conclusions:
- Cefazolin inoculum effect (CzIE) is associated with a substantially increased risk of microbiological treatment failure in MSSA infections.
- CzIE testing may serve as a valuable tool for guiding cefazolin treatment decisions in serious MSSA infections.
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