Comparison of Oral Cephalosporin and Penicillin Step-Down Therapy for the Treatment of Gram-Negative Blood Stream Infections: A Retrospective Observational Study.

Abstract

Background: Oral step-down therapy for the treatment of gram-negative blood stream infections (GNBSIs) has been shown to be noninferior to full courses of intravenous (IV) therapy. Studies comparing oral fluoroquinolones, sulfamethoxazole-trimethoprim (SMX-TMP), and beta-lactams have reported similar treatment outcomes, but beta-lactam groups have been small, and efficacy has been questioned given lower oral bioavailability.

Objective: This study aims to evaluate the safety and efficacy of oral cephalosporins compared with penicillins for step-down therapy for the treatment of GNBSI.

Methods: This was a retrospective study in adult patients admitted for Enterobacterales GNBSI that were transitioned from IV antibiotics to an oral beta-lactam. The primary outcome was treatment failure. Secondary outcomes included components of the primary outcome, microbiological failure, antibiotic-associated adverse drug events (ADEs), and Clostridioides difficile infection (CDI).

Results: Overall, 280 patients with GNBSI with step-down to an oral penicillin (n = 140) or cephalosporin (n = 140) were included. More patients in the cephalosporin group had a urinary source of infection (87.9% vs 62.1%, P < 0.001) and urinary abnormalities (40% vs 28.6%, P = 0.044). Treatment failure with oral cephalosporins was noninferior to penicillins (7.1% vs 7.1%; 95% confidence interval [-6.4, 6.4], P = 0.002). No significant differences were found for microbiological failure, antibiotic-associated ADEs, or CDI.

Conclusion and relevance: Oral cephalosporins were noninferior to oral penicillins as step-down therapy for Enterobacterales GNBSI. This represents the first comparison of oral beta-lactams for the treatment of GNBSI.