Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates.

TitlePrevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates.
Publication TypeJournal Article
Year of Publication2022
AuthorsDingle TC, Gamage D, Gomez-Villegas S, Hanson BM, Reyes J, Abbott A, Burnham C-AD, Bard JDien, Fritz S, Miller WR, Westblade LF, Zimmer B, Arias CA, Butler-Wu S
Corporate AuthorsCLSI Cefazolin High Inoculum Ad-Hoc Working Group
JournalJ Clin Microbiol
Volume60
Issue7
Paginatione0249521
Date Published2022 Jul 20
ISSN1098-660X
KeywordsAnti-Bacterial Agents, Bacteremia, Cefazolin, Humans, Methicillin, North America, Prevalence, Staphylococcal Infections, Staphylococcus aureus
Abstract

Antistaphylococcal penicillins and cefazolin remain the primary treatments for infections with methicillin-susceptible Staphylococcus aureus (MSSA). The cefazolin inoculum effect (CzIE) causes the cefazolin MIC to be elevated in proportion to the number of bacteria in the inoculum. The objective of this multicenter study was to evaluate the prevalence of the CzIE in North American MSSA isolates. Clinical MSSA isolates from six microbiology laboratories in the United States and one microbiology laboratory in Canada were screened for the CzIE by broth microdilution at a standard inoculum (~5 × 105 CFU/mL) and a high inoculum (~5 × 107 CFU/mL). Genome sequencing was performed to further characterize the MSSA isolates. The CzIE was present in 57/305 (18.6%) MSSA isolates, ranging from 0% to 27.9% across study sites. More of the CzIE-positive isolates (29.8%) had standard inoculum cefazolin MICs of 1.0 μg/mL than the CzIE-negative isolates did (3.2%) (P < 0.0001). Conversely, more CzIE-negative isolates (39.5%) had standard inoculum MICs of 0.25 μg/mL than the CzIE positive isolates did (5.3%) (P < 0.0001). The most common BlaZ β-lactamase types found in the CzIE-positive strains were type C (53.7%) and type A (44.4%). ST8 and ST30 were the most common sequence types among CzIE-positive isolates and correlated with BlaZ type C and A, respectively. The CzIE was present in up to a quarter of clinical MSSA isolates from North American clinical laboratories. Further studies to determine the impact of the presence of the CzIE on clinical outcomes are needed.

DOI10.1128/jcm.02495-21
Alternate JournalJ Clin Microbiol
PubMed ID35578988
PubMed Central IDPMC9297818
Grant ListP01 AI152999 / AI / NIAID NIH HHS / United States
R21 AI143229 / AI / NIAID NIH HHS / United States
R01 AI134637 / AI / NIAID NIH HHS / United States
K24 AI121296 / AI / NIAID NIH HHS / United States
R01 AI148342 / AI / NIAID NIH HHS / United States
K08 AI135093 / AI / NIAID NIH HHS / United States
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