Effects of an Intervention to Substitute Cefazolin for Nafcillin in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia

Background: Anti-staphylococcal penicillins are considered first-line therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but are costly and are associated with adverse drug events.  Cefazolin is inexpensive and may be associated with fewer adverse events, but has been less well-studied.  We aimed to evaluate the impact of an intervention to use cefazolin in lieu of nafcillin in selected cases of MSSA bacteremia at an academic public safety-net hospital.

Methods: In February 2010, the antibiotic stewardship team implemented an intervention to substitute cefazolin for nafcillin in cases of MSSA bacteremia not associated with endovascular or central nervous system involvement.  We performed a retrospective cohort study of patients with MSSA bacteremia from February 2008 – January 2010 (pre-intervention) and February 2010 – September 2012 (post-intervention).  The primary outcome was the change in cefazolin and nafcillin use.  Secondary outcomes included change in the rate of adverse events (laboratory abnormalities or C. difficile infection), clinical failure (bacteremia >7 days, recurrence, or death), and antibiotic acquisition costs.

Results: 33 cases in the pre-intervention period and 36 in the post-intervention period were included.  Five (15%) and 3 (8%) cases of endovascular infection were diagnosed in each time period, respectively.  Cefazolin use increased from 55% to 75% of cases before and after the intervention, respectively (p = .07).  Duration of cefazolin as a proportion of the total duration of therapy increased from 31% to 52% (p = .04).  Nafcillin use decreased from 58% to 25% of cases, respectively (p = .006).  Duration of nafcillin as a proportion of the total duration decreased from 26% to 16% (p = .03).  Adverse events occurred in 12 (36%) and 15 (42%) cases (p = .65), respectively; clinical failure occurred in 5 (15%) and 6 (17%) cases (p = 0.87).  Total antibiotic acquisition costs decreased by 14% ($31,549 vs. $27,271).

Conclusion: An intervention to substitute cefazolin for nafcillin in selected cases of MSSA bacteremia was associated with increased cefazolin use, decreased nafcillin use, and lower antibiotic costs.  Although rates of adverse events and clinical failure were similar between the periods, larger studies are needed to confirm the safety and efficacy of this approach.