Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

Abstract

e Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P ‫؍‬ 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P ‫؍‬ 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P ‫؍‬ 0.05) and to have an osteoarticular source (57% versus 33%; P ‫؍‬ 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P ‫؍‬ 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P ‫؍‬ 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P ‫؍‬ 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.

Treatment Outcomes with Cefazolin versus Oxacillin for Deep-Seated Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

“…Our results are consistent with those from other related recently published studies (12,16,17,27). However, in comparison to previous studies, we observed higher rates of endocarditis, in which 16.5% (17/103) of patients carrying the diagnosis of infectious endocarditis were treated with cefazolin, and 20.7% (n ϭ 12/58) were treated with oxacillin.…”

“…We did not detect differences in efficacy according to study center, and the inclusion of the study center in our multivariate models failed to significantly improve predictions of failure. Recent studies have observed higher discontinuation rates with semisynthetic penicillins than with cefazolin (17,27), which may partially explain the findings in our composite endpoint of slightly higher failure rates with oxacillin than with cefazolin. However, we did not detect significant differences in the adverse drug events between these agents.…”

“…Furthermore, current practice guidelines, such as those for infective endocarditis, suggest reserving the use of cefazolin for patients with nonanaphylactoid-type penicillin allergies (7). As a result, clinician preference for either nafcillin or oxacillin for more severe or deep-seated MSSA infection has evolved in practice, while the use of cefazolin in this setting remains controversial (12,16,17). The purpose of this study was to evaluate and compare treatment outcomes using cefazolin or oxacillin for MSSA BSI, including deep-seated sources of infection.…”

Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center

“…The adjusted estimate was in the opposite direction (aOR, 1.2; 95% CI 0.3 to 4.5; P ϭ 0.76) but again with very wide uncertainty. A study by Li et al (15) found a statistically significant difference in the comparison of the raw proportions of failures in cefazolin and oxacillin groups, 24% versus 47% (P ϭ 0.04), but did not present a multivariate-adjusted effect size estimate or confidence interval, although choice of antimicrobial was not statistically significantly associated with treatment failure in a multivariate model (P ϭ 0.36). Paul et al also examined the association between receipt of cefazolin (compared to oxacillin) and death at 90 days (as measured by a national death registry) in MSSA BSI cases and found a reduction in the odds of death (aOR, 0.81) but a wide confidence interval (95% CI, 0.18 to 3.62) (17).…”

“…However, several observation studies suggest treatment failure is not more common with cefazolin than with antistaphylococcal penicillins (15)(16)(17), and a recent large Canadian observational study found a substantial mortality reduction in those receiving cefazolin compared to those receiving cloxacillin (18), although this hazard reduction was not statistically significant (18). Thus, further data on the comparative outcomes for MSSA BSI treated by cefazolin or antistaphylococcal penicillins are needed to clarify whether either of these treatment options is superior.…”