Nannini EC, Stryjewski ME, Singh KV, Bourgogne A, Rude TH, Corey GR, Fowler VG, Murray BE
Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin Susceptible Staphylococcus aureus: Frequency and Possible Cause of Cefazolin Treatment failure. [JOURNAL ARTICLE]
Antimicrob Agents Chemother 2009 Jun 1.
Methicillin-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-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, none type D, and 13% lacked blaZ. The cefazolin MIC90 was 2 ug/ml at standard inoculum and 32 ug/ml at high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MIC >/=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than types B or C while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the 6 patients that experienced cefazolin failure showed a cefazolin inoculum effect while none from the 6 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 in hemodialysis patients with MSSA bacteremia. These results suggest that, in 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 used at low doses.
More from this journal |
