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Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible

Tanis C Dingle1,2, Dulini Gamage3, Sara Gomez-Villegas4,5

  • 1Alberta Precision Laboratories-Public Health Laboratory, Calgary, Alberta, Canada.

Journal of Clinical Microbiology
|May 17, 2022
PubMed

Insights

The cefazolin inoculum effect (CzIE), a phenomenon impacting methicillin-susceptible Staphylococcus aureus (MSSA) treatment, was found in 18.6% of North American isolates. This prevalence highlights potential challenges in cefazolin efficacy for MSSA infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Methicillin-susceptible Staphylococcus aureus (MSSA) infections are commonly treated with antistaphylococcal penicillins and cefazolin.
  • The cefazolin inoculum effect (CzIE) is a phenomenon where cefazolin's minimum inhibitory concentration (MIC) increases with higher bacterial concentrations.
  • Understanding the prevalence of CzIE in clinical isolates is crucial for assessing cefazolin's effectiveness.

Purpose of the Study:

  • To determine the prevalence of the cefazolin inoculum effect (CzIE) in clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) across North America.
  • To characterize the genetic features, including beta-lactamase types and sequence types, associated with CzIE-positive MSSA isolates.

Main Methods:

  • A multicenter study involving seven microbiology laboratories in the United States and Canada.
  • Clinical MSSA isolates were tested for CzIE using broth microdilution at standard (~5 × 10^5 CFU/mL) and high (~5 × 10^7 CFU/mL) inoculums.
  • Genome sequencing was employed to characterize the genetic makeup of the isolates, focusing on BlaZ beta-lactamase types and sequence types (STs).

Main Results:

  • The CzIE was detected in 18.6% (57/305) of the tested MSSA isolates, with prevalence varying by study site (0% to 27.9%).
  • CzIE-positive isolates were significantly more likely to have higher cefazolin MICs at standard inoculum (1.0 μg/mL) compared to CzIE-negative isolates.
  • BlaZ types C and A were most common in CzIE-positive strains (53.7% and 44.4%, respectively), often associated with ST8 and ST30, respectively.

Conclusions:

  • The cefazolin inoculum effect is present in a notable proportion of clinical MSSA isolates in North American laboratories.
  • Specific beta-lactamase types (BlaZ C and A) and sequence types (ST8 and ST30) are associated with the CzIE in MSSA.
  • Further research is necessary to elucidate the clinical impact of the CzIE on treatment outcomes for MSSA infections.
Keywords:
MSSAStaphylococcus aureuscefazolininoculum effect

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