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

Abstract

d Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P ‫؍‬ 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study. Staphylococcus aureus is a leading cause of both communityonset and hospital-acquired bloodstream infection (BSI) (1, 2). S. aureus BSI (SABSI) has a considerable disease burden throughout the world, with an estimated incidence of 19.7 to 50 per 100,000 person-years (3, 4) and a contemporary 30-day mortality rate of 20%, although this estimate varies considerably by study (20 to 36%) (4, 5).While methicillin-resistant S. aureus (MRSA) is often the focus of S. aureus surveillance (6-8), methicillin-sensitive S. aureus (MSSA) BSI still accounts for the majority of SABSI in many regions (9, 10). Some recent data suggest that, adjusting for host factors and other confounders, mortality outcomes in MSSA BSI are equivalent to those in MRSA BSI, although this is controversial (4, 11).The preferred antimicrobial agents for MSSA BSI are generally either the antistaphylococcal penicillins (nafcillin, flucoxacillin, cloxacillin, or oxacillin, depending on local antibiotic availability) or cefazolin, a first-generation cephalosporin (12, 13). While both options are widely used in clinical practice and toxicities exist with each of these antimicrobials, cefazolin has possible advantages over antistaphylococcal penicillins for the treatment of MSSA BSI, including less frequent dosing and dialysis dosing regimens for those on hemodialysis with limited venous access (12, 13).A concern with cefazolin is that some strains exh...

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

“…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.…”

Ability of Bicarbonate Supplementation to Sensitize Selected Methicillin-ResistantStaphylococcus aureus(MRSA) Strains to β-Lactam Antibiotics in anEx VivoSimulated Endocardial Vegetation Model

“…The treatment of MRSA infections poses several daunting challenges. Current treatment options for MRSA infections are relatively limited, and include antibiotics that are not only costly, but also substantially less effective, and often more toxic when compared to standard antibiotic treatments for MSSA (25-27). This is in large part due to the perceived inability to use traditional β-lactam antibiotics for MRSA infections (6).…”

“…There remains a current debate over the most appropriate β-lactam to treat serious MSSA infections, with CFZ or OXA as the primary candidates (25, 39); most recent MSSA bacteremia studies appear to favor CFZ (16, 26, 27). Further, on balancing adverse events vs efficacy metrics, CFZ is generally regarded as a safer option, due to its decreased renal toxicity risk as compared to the antistaphylococcal penicillins (16, 27). However, there remains concern about CFZ efficacy in “high-inoculum” S. aureus infections (e.g., endocarditis) due to the potential for the undetected presence and induction of genes for Types A or C cephalosporinases that hydrolyze CFZ (39, 40).…”

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible <b><i>Staphylococcus aureus</i></b> Bloodstream Infections

“…The overall rates of adverse drug effects were 7.8% in the cefazolin arm and 3.5% in the oxacillin arm ( p = 0.33). Pollett et al [8] reported a retrospective, single-center cohort study of 30 patients receiving nafcillin and 70 patients receiving cefazolin for treatment of MSSA BSI in which mortality rates at 90 days were 16.7% in the nafcillin group and 7.1% in the cefazolin group. The unadjusted odds ratio for 90-day mortality in patients receiving cefazolin was 0.38 (95% confidence interval 0.10–1.44; p = 0.16).…”