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

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.