Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea

Abstract

Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

“…The failure to reach statistical significance may be due to the fact that the CzIE as defined in this study did not require the isolate to be above the susceptibility cutoff. A recent prospective study of nafcillin vs cefazolin by the same group included a small subset of patients treated with cefazolin for which the presence of CzIE in the isolate was assessed [28]. Overall, 22.4% of isolates were positive for the CzIE, and those treated with cefazolin, but not nafcillin, were statistically more likely to have clinical failure or death within 1 month of positive culture when infected with a CzIE-positive isolate.…”

Meta‐analysis of trials comparing cefazolin to antistaphylococcal penicillins in the treatment of methicillin‐sensitive Staphylococcus aureus bacteraemia

“…It is possible that cefazolin would be less efficacious than ASP in these settings since more severe infection may predispose to an inoculum effect to cefazolin, which could result in treatment failure. Inoculum effect is Lee et al [15] Year published No. of patients reviewed Cef -3 g day -1…”

“…However, concerns regarding the cefazolin inoculum effect leading to treatment failure, especially for deep seated infections, has dampened the enthusiasm for using cefazolin in MSSA bacteraemias. Emerging data now suggest that cefazolin may be equally or actually more effective than ASP in improving mortality for MSSA bacteraemias with fewer adverse effects, although the data are not uniform [6][7][8][9][10][11][12][13][14][15]. Therefore, we decided to identify these comparative trials, pool the data and perform a meta-analysis to assess the efficacy and safety of cefazolin when compared to ASP in the treatment of MSSA bacteraemias.…”

Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis

“…Recent data from a prospective clinical study in Argentina where cephalosporins were used as a first-line therapy showed that patients infected with MSSA isolates exhibiting the CzIE were significantly more likely to have higher 30-day all-cause mortality (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.10 to 6.42; P ϭ 0.03) than those without the effect (15). A study in Korea supported these observations, as patients with CzIE-positive isolates treated with cefazolin were noted to have increased rates of treatment failure (61.5% versus 28.9%, P ϭ 0.049) or increased all-cause mortality at 1 month (15.4% versus none, P ϭ 0.047) compared to those with CzIE-negative isolates (14). This effect was not seen in those patients who received nafcillin, suggesting that the CzIE itself, and not the increased virulence of these strains, drives treatment failure.…”

“…In a previously described experimental model of endocarditis in rats, an MSSA isolate positive for the CzIE was associated with significantly higher bacterial counts in vegetations when treated with cefazolin compared to those with nafcillin, ceftaroline, or daptomycin (12,13). Furthermore, prospective observational data on the use of cefazolin in patients with MSSA bacteremia where the presence of the CzIE was assessed demonstrated that CzIE-positive isolates were associated with a significant increase in therapeutic failure and mortality (14,15). Thus, strategies to preserve the usefulness of cefazolin in the setting of the CzIE are needed.…”