Can patients with S. aureus bacteremia be switched to oral therapy after 5-7 days of IV therapy?
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In a study published in Lancet Infectious Diseases, Kaasch et al. assessed the efficacy and safety of an early switch to oral therapy in patients with low-risk S. aureus bacteremia. They carried out a multicenter, open-label, randomized, noninferiority trial in Europe. Patients with S. aureus bacteremia were enrolled after 5 to 7 days of intravenous therapy and randomized to oral therapy or to continue IV therapy. The researchers excluded patients with endocarditis, pneumonia, infected implants, osteomyelitis, septic shock, bacteremia for > 72 hours, recurrent bacteremia, severe immunodeficiency, prosthetic heart valves or vascular grafts. Oral antibiotics were trimethoprim-sulfamethoxazole (160/800 mg q12h), clindamycin (600 mg q8h) or linezolid (600 mg q12h). IV antibiotics were flucloxacillin, cefazolin, vancomycin or daptomycin.
The composite primary endpoint was the occurrence of any complication related to S. aureus bacteremia (relapsing bloodstream infection, deep-seated infection and mortality attributable to infection) within 90 days, measured in the intention-to-treat population. The calculated sample size was 430 participants. However, due to slow recruitment, the scientific advisory committee stopped the trial after randomizing 215 participants and changed the noninferiority margin from 5% to 10%.
Of 5,063 patients with S. aureus bacteremia assessed for eligibility, 108 were randomly assigned to switch to oral therapy and 105 to continue IV therapy. The mean age was 63.5 years, 65 (31%) patients were female, and 16 (8%) patients had methicillin-resistant S. aureus bacteremia. Seventy-one (66%) patients in the oral switch group and 71 (68%) in the IV group had venous catheter-related bacteremia.
Participants received a median of 6 days of IV therapy in both groups before treatment assignment. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the IV group, with a treatment difference of 0.7 percentage points (95% confidence interval, -7.8 to 9.1; P = .01). The median length of hospital stay after the first positive blood culture was 12 days in the oral switch group versus 16 days in the IV group (median difference, -2 days; 95% confidence interval, -4 to 0; P = .04).
Complications of IV administration were found in 9% and 17% of patients in the oral switch group and IV group, respectively (treatment difference, -7.9 percentage points; 95% CI, -17.6 to 1.9). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the IV group (P = .29). Survival at 90 days was 83.6% in the oral switch group versus 89% in the IV group (difference, -5.4 percentage points; 95% CI, -14.8 to 4). There were two deaths due to S. aureus bacteremia in the oral switch group and none in the IV group.
Although the authors concluded that oral switch antibiotic therapy was noninferior to IV therapy, it is important to consider that oral therapy would not have met noninferiority if the original noninferiority margin had not been changed. Furthermore, the generalization to patients with MRSA bacteremia is limited. It is also concerning that serious adverse events and deaths due to S. aureus bacteremia were more common in the oral switch group compared with the IV group, although these differences were not statistically significant. Overall, this is an important study that opens the possibility of using oral antibiotics in low-risk patients with S. aureus bacteremia, but larger studies are needed to ensure oral therapy is not associated with worse outcomes after 5 to 7 days of IV therapy.
