Validation of a modified rapid test to detect the cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus from bloodstream infections in hospitals from North and Latin America.

Summary

In 200 MSSA bloodstream isolates from North and Latin America, a blinded modified nitrocefin test using ampicillin disks detected the cefazolin inoculum effect with 96% sensitivity and 91.6% specificity versus high-inoculum MIC. The assay showed 94% overall accuracy and no false positives among blaZ-negative strains, offering a low-cost, scalable tool.

Key Findings

• CzIE prevalence among 200 MSSA bloodstream isolates was 53% (105/200).
• Modified nitrocefin test achieved 96% sensitivity, 91.6% specificity, and 94% accuracy versus high-inoculum MIC.
• No false positives were observed among blaZ-negative MSSA strains.
• Whole-genome sequencing enabled performance assessment across BlaZ types.

Clinical Implications

Clinical microbiology labs can adopt this rapid screen to identify CzIE and guide antibiotic selection (e.g., opting for anti-staphylococcal penicillins when CzIE is present) to optimize outcomes.

Limitations

• Laboratory validation without direct linkage to patient-level outcomes.
• Focused on MSSA; generalizability to other organisms or settings may be limited.

Future Directions

Prospective clinical studies linking CzIE detection to antibiotic choices and outcomes; implementation research in low-resource settings; automation/integration into lab workflows.