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

Abstract

Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Ability of Bicarbonate Supplementation To Sensitize Selected Methicillin-Resistant Staphylococcus aureus Strains to β-Lactam Antibiotics in an Ex Vivo Simulated 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 compared to standard antibiotic treatments for MSSA (21)(22)(23). This is in large part due to the perceived inability to use traditional ␤-lactam antibiotics for MRSA infections (2).…”

Retrospective Analysis of Adverse Drug Events Between Nafcillin Versus Cefazolin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections

“…18 Another recent retrospective study evaluating 130 patients with MSSA bacteremia at a tertiary academic medical center reported a higher incidence of nephrotoxicity with nafcillin compared with cefazolin (25% vs 2%, respectively; relative risk = 1.31), utilizing an increase in SCr ≥1.5 times or by 0.5 mg/dL from baseline levels as nephrotoxicity criteria. 19 Burrelli et al 20 reported a higher incidence of AKI with nafcillin compared with cefazolin (29.1% vs 15.4%, respectively), utilizing a definition during hospital stay with an increase in SCr ≥0.5 mg/dL or 50% increase from baseline. In contrast, Youngster et al 11 reported nafcillin AKI rates of 11.4% when used for MSSA infections in the outpatient setting.…”

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

“…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).…”