Oral switch vs. continued intravenous antibiotic therapy in patients with bacteraemia and sepsis: a systematic review and meta-analysis

Abstract

Background: Bacteraemia and sepsis have traditionally required continued intravenous (IV) antibiotics.

Objectives: This study aims to evaluate if early transition to oral antibiotics is non-inferior to continued IV antibiotic therapy in treating patients with bacteraemia and sepsis.

Data sources: Data sources include MEDLINE, Embase, Web of Science, the Cochrane Library, and Wanfang databases from inception to 13 July 2024, along with clinical trial registries and Google.com.

Study eligibility criteria: Study eligibility criteria include randomized controlled trials (RCTs) and cohort studies.

Participants: Participants include patients with bacteraemia and sepsis.

Interventions: Interventions include early transition to oral antibiotics vs. continued IV antibiotics. Early oral switch was defined as 5-9 days for uncomplicated Staphylococcus aureus bacteraemia, <4 weeks for complicated S. aureus bacteraemia, 3-7 days for uncomplicated Streptococcus bacteraemia, and 3-5 days for uncomplicated Enterobacterales bacteraemia.

Assessment of risk of bias: Assessment of risk of bias includes Cochrane risk of bias tool and Newcastle-Ottawa Scale.

Methods of data synthesis: Random-effect models were used to pool the data. The primary outcome was treatment failure. The non-inferiority margin for treatment failure was 10%. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to rate the certainty of the evidence.

Results: In total, 38 studies (6 RCTs, 10 adjusted cohorts, and 22 unadjusted cohorts) involving 11 566 patients were included. A primary analysis of 6 RCTs and 10 adjusted cohorts comprised 7102 patients. High-certainty evidence from six RCTs showed that early transition to oral antibiotics was non-inferior to continued IV therapy for treatment failure (n = 529; OR 0.89; 95% CI: 0.54-1.48). Low-certainty evidence from five adjusted cohorts also found no significant difference in treatment failure between the two groups (n = 929; OR 0.60; 95% CI: 0.29-1.72). Moderate-certainty evidence showed that oral switch therapy significantly reduced hospital stay (n = 2041; mean difference: -5.19 days; 95% CI: -8.16 to -2.22).

Conclusions: Early transition to oral antibiotics was non-inferior to continued IV antibiotic treatment for bacteraemia and sepsis.

Keywords: Antibiotic; Bacteraemia; Meta-analysis; Oral therapy; Sepsis; Switch.