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Comparative Effectiveness of Third-Generation Cephalosporins Versus Penicillinase-Stable Penicillins for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study

Year: 2015

Type: article

Abstract: Background. Third-generation cephalosporins (e.g. ceftriaxone) could be a convenient therapy for MSSA infections complicated by bacteremia, due to its once daily dosing. This study compared definitive therapy with the third generation cephalosporins ceftriaxone and cefotaxime (3GC) with penicillinase-stable penicillins (PSP) (e.g. nafcillin or oxacillin) among patients with MSSA infections complicated by bacteremia. Methods. This retrospective cohort study included patients admitted to 121 Veterans Health Administration hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with ceftriaxone, cefotaxime, nafcillin, or oxacillin. Definitive therapy was defined as the receipt of an antimicrobial between 4 to 14 days after the first positive blood culture was collected. Cox proportional hazard regression and ordinal logistic regression (categories: no recurrence, recurrence, death) were used to examine the association between treatment and recurrence or death. Recurrent MSSA infections were defined as a MSSA positive blood culture between 45 to 365 days after the first MSSA positive blood culture. Results. Of 2642 patients, 609 (23%) patients received therapy with a 3GC. Both 30-day mortality (hazards ratio (HR): 1.06; 95% confidence interval (CI): 0.83-1.37) and 90-day mortality (HR: 1.16; 95% CI: 0.95-1.40) were similar between patients who received 3GC compared with patients who received PSP after controlling for severity of illness, comorbidity score, age, skin and soft tissue infections, endocarditis, osteomyelitis, hepatitis C, and diabetes. Additionally, the odds of having a recurrent infection were similar for patients who received 3GC compared with patients who received PSP after controlling for those factors (odds ratio: 1.01; 95% CI: 0.80-1.29). Conclusion. In this large, multi-center study, a significant difference was not observed among patients receiving therapy with 3GC compared with patients receiving PSP for MSSA infections complicated by bacteremia. If validated in an individually randomized trial, 3GC might be an appropriate definitive therapy for treating patients with MSSA infections complicated by bacteremia. Disclosures. E. Perencevich, Cubist Pharmaceuticals, inc: Grant Investigator, Research grant

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofv133.557