Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: Frequency and possible cause of cefazolin treatment failure

Esteban C. Nannini, Martin E. Stryjewski, Kavindra V. Singh, Agathe Bourgogne, Tom H. Rude, G. Ralph Corey, Vance G. Fowler, Barbara E. Murray

Research output: Contribution to journalArticlepeer-review

Abstract

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥ 16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Original languageEnglish (US)
Pages (from-to)3437-3441
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number8
DOIs
StatePublished - Aug 2009

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: Frequency and possible cause of cefazolin treatment failure'. Together they form a unique fingerprint.

Cite this