Should Cefazolin be Preferred Treatment for Methicillin-susceptible S. aureus Bacteremia Instead of Nafcillin?
By Richard R. Watkins, MD, MS, FACP, Division of Infectious Diseases, Akron General Medical Center, Akron, OH
Assistant Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
Synopsis: In a retrospective, propensity-score-matched, case-control study, investigators compared clinical outcomes and drug tolerabilities between nafcillin and cefazolin in the treatment of MSSA bacteremia. The authors found that cefazolin was as efficacious as nafcillin in the treatment of MSSA bacteremia while causing fewer adverse drug events
Source: Lee S, et al. Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia? Antimicrob Agents Chemother 2011;55:5122-6.
Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is a commonly encountered infection in hospitalized patients that can have serious complications if not adequately treated. In a retrospective, propensity-score-matched, case-control study, investigators compared clinical outcomes and drug tolerabilities between nafcillin and cefazolin in the treatment of MSSA bacteremia. The study was conducted between 2004 and 2009 at a tertiary care center in Seoul, South Korea. From August 2004 to August 2006 nafcillin was not available at the hospital because of supply issues. Patients with MSSA bacteremia were mainly treated with cefazolin during that period.
The authors examined the medical records of all patients with MSSA-positive blood cultures between January 2004 and June 2009 who received either nafcillin or cefazolin and placed them in two groups based on the antibiotic used. Logistic regression was used to create a propensity score based on risk factors for each patient. These risk factors included age, McCabe classification, high-burden disease, site of infection, and focus eradication. Patients in the cefazolin group were matched with patients in the nafcillin treatment group who had the closest propensity scores. The treatment failure rates were compared between the propensity-score-matched-groups 4 and 12 weeks after the start of nafcillin or cefazolin treatment.
Out of 174 patients during the study period with MSSA bacteremia, 84 were treated with nafcillin and 90 were treated with cefazolin. Forty-one patients in the cefazolin group were matched with the 41 patients in the nafcillin group with the highest propensity scores. Times to defervescence were 4.4 ± 4.9 days in the matched cefazolin group and 5.4 ± 9.3 days in the matched nafcillin group (p=0.63). The treatment failure rates at 12 weeks were 15% (6/41) in the cefazolin group and 15% (6/41) in the nafcillin group (p >0.99). The rates of MSSA bacteremia-related mortality were 2% (1/41) in the cefazolin group and 12% (5/41) in the nafcillin group (p =0.22). There was no significant difference between the two groups in 4 week mortality (4% vs. 4%). In four patients in the cefazolin group, the antibiotic was changed due to treatment failure (3 to vancomycin, 1 to nafcillin). Pneumonia and infective endocarditis have been previously shown to be predictors of treatment failure for MSSA bacteremia. After adjusting for these risk factors, cefazolin use was found to not be a risk factor for treatment failure for MSSA bacteremia.
None of the patients in the cefazolin group had their treatment interrupted due to adverse drug events. In contrast, 7 patients discontinued nafcillin because of adverse events including fever (n=4), cytopenia (n=2), and phlebitis (n=1). The median time to the discontinuation of nafcillin was 19 days (range, 7 to 24 days).
Commentary
The authors of this study found that cefazolin was as efficacious as nafcillin in the treatment of MSSA bacteremia while causing fewer adverse drug events. One limitation is the retrospective design which could predispose to selection bias, although the authors attempted to compensate for this by using propensity scores and included patients in the cefazolin group when nafcillin was unavailable at the institution. Another limitation was that few endocarditis cases were treated with cefazolin (n =1). The number of patients in both treatment groups was small (n =41) which could limit the ability to detect differences in outcomes between nafcillin and cefazolin.
While a randomized, prospective clinical trial comparing nafcillin to cefazolin for treatment of MSSA bacteremia would be welcomed, it seems unlikely such a study will be conducted in the near future. Therefore clinicians must decide how to treat patients with MSSA bacteremia based on the best available evidence. Using cefazolin in this scenario seems to be a reasonable approach. In addition to fewer adverse drug events than nafcillin, cefazolin has a more convenient dosing schedule (every 8 hours compared to every 4 hours) and can be given at the end of a dialysis session in patients with renal failure. One caveat is that nafcillin should probably remain the first line therapy for MSSA endocarditis with brain emboli. Cefazolin poorly penetrates the blood-brain barrier, so metastatic infection of the brain from endocarditis might not be adequately treated with this drug. However, it is controversial and further studies on this are warranted.
Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is a commonly encountered infection in hospitalized patients that can have serious complications if not adequately treated.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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