IV to oral antibiotic switch noninferior to continuous IV in enterobacterales BSI

Among patients with enterobacterales bloodstream infection (BSI), switching from intravenous (IV) to oral antibiotics is noninferior to continuous IV antibiotic therapy in reducing treatment failure within 90 days, according to a study presented at ECCMID 2023.

Large-scale surveys have shown that most physicians continue to believe that IV antibiotics are necessary for patients with gram-negative bacteraemia in general. However, “we all know that this assumption is not based on robust clinical evidence,” said lead author Dr Ali Omrani from the College of Medicine at Qatar University in Doha, Qatar. 

“The evidence-based to reassure physicians that a switch from IV to oral antibiotics in patients with enterobacterales bacteremia is not necessarily present,” he noted.

The researchers conducted a pragmatic, multicentre, open-label, noninferiority trial involving 174 adults (mean age 56.6 years, 51 percent female) with monomicrobial enterobacterales BSI who were recruited from 11 centres in Qatar, Turkey, Kuwait, and Bahrain. Prior to randomization, all patients received and completed 3–5 days of IV antibiotic therapy. Participants were randomized to continuous IV (n=85) or oral switch (n=89) therapy. [ECCMID 2023, abstract O0328]

The primary endpoint of the study was treatment failure, defined as a composite of death from any cause, need for any additional active antimicrobial therapy before complete resolution of signs and symptoms of infection, microbiological relapse, and infection-related readmission within 90 days.

Omrani highlighted that “the composite endpoint of this study was designed to capture treatment failures, not just traditionally in mortality but other meaningful clinical outcomes as well.”

In the modified intention-to-treat analysis, the incidence of treatment failure did not differ between the IV and oral switch groups at 90 days of follow-up (25.6 percent vs 21.7 percent), and this translated to a risk difference of -3.7 percent.

When assessing individual components of treatment failure, the mortality rates were low and comparable in both the IV and oral groups (3.7 percent vs 3.6 percent; risk difference -0.1 percent).

The need for additional therapy and microbiological relapse occurred more frequently in the IV group than the oral group (12.2 percent vs 4.8 percent; risk difference, -7.1 percent and 12.2 percent vs 7.2 percent; risk difference, -4.8 percent, respectively).

However, a higher incidence of infection-related re-admission was observed in the oral group vs the IV group (18.1 percent vs 11.0 percent), though the oral group had a significantly shorter hospital length of stay (ratio, 0.74; p=0.01).

With regard to adverse events (AEs), both IV and oral groups showed similar rates of grade 3–5 AEs (21.2 percent vs 23.6 percent) and serious AEs (18.8 percent vs 21.3 percent), as well as AEs leading to treatment discontinuation (2.4 vs 1.1 percent), which was very low.