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Updated: Feb 8, 2026
Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
Published on: February 9, 2011
The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus
William R Miller1,2, Carlos Seas3, Lina P Carvajal4
1Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas.
Background:
Recent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated.
Methods:
We prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates.
Results:
A total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10-6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage.
Conclusions:
In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.
Insights
The cefazolin inoculum effect (CzIE) in methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is linked to higher mortality. This finding suggests caution when using cefazolin as a primary treatment for severe MSSA infections.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Pharmacology
Background:
- Cefazolin is increasingly preferred over nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.
- The cefazolin inoculum effect (CzIE) is a phenomenon where higher bacterial concentrations increase cefazolin's minimum inhibitory concentration (MIC).
- The clinical impact of CzIE on severe MSSA infections treated with cephalosporins remains unevaluated.
Purpose of the Study:
- To investigate the clinical significance of the cefazolin inoculum effect (CzIE) in patients with MSSA bacteremia.
- To determine if CzIE is associated with treatment outcomes, specifically 30-day mortality.
Main Methods:
- Prospective study of patients with S. aureus bacteremia across three Argentinian hospitals.
- Determination of cefazolin MICs at standard (10^5 CFU/mL) and high (10^7 CFU/mL) inoculums to identify CzIE (MIC ≥16 µg/mL at high inoculum).
- Whole-genome sequencing of MSSA isolates and multivariate analysis of clinical data.
Main Results:
- Of 89 MSSA isolates, 42 (54.5%) exhibited the CzIE.
- Patients with MSSA isolates showing CzIE had significantly higher 30-day mortality (P = .03) and were more likely to have catheter-associated or unknown bacteremia sources (P = .033).
- CzIE remained an independent predictor of increased 30-day mortality in multivariate analysis (RR, 2.65; P = .03).
Conclusions:
- The cefazolin inoculum effect (CzIE) is associated with increased 30-day mortality in MSSA bacteremia patients treated with cephalosporins.
- Clinicians should exercise caution when using cefazolin as first-line therapy for MSSA infections, especially if CzIE is suspected.
- Further research may be needed to optimize antibiotic strategies for MSSA bacteremia influenced by inoculum effects.
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