SIMPLIFY (post-hoc analysis)
Trial question
What is the effect of early oral switch in patients with bloodstream infections caused by Enterobacterales?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 303
303 patients (124 female, 179 male).
Inclusion criteria: patients with bloodstream infections caused by Enterobacterales who achieved clinical stability by day 5.
Key exclusion criteria: life expectancy < 30 days; pregnancy or lactation; isolation of carbapenemase-producing Enterobacterales; severe neutropenia; planned duration of treatment > 28 days.
Interventions
N=110 early oral switch (switched to oral therapy on day 5).
N=193 continued IV therapy (either switched later or remained on intravenous therapy for full treatment duration).
Primary outcome
Clinical cure at test of cure
95.4%
91.7%
95.4 %
71.6 %
47.7 %
23.9 %
0.0 %
Early oral
switch
Continued IV
therapy
No significant
difference ↔
No significant difference in clinical cure at test of cure (95.4% vs. 91.7%; RR 1.04, 95% CI 0.98 to 1.1).
Secondary outcomes
Significant increase in clinical cure at day 60 (96.3% vs. 84.9%; RR 1.13, 95% CI 1.06 to 1.21).
No significant difference in death at day 60 (2.7% vs. 5.2%; RR 1.02, 95% CI 0.98 to 1.07).
Significant decrease in the rate of recurrence until day 60 (10.9% vs. 24.3%; RR 0.45, 95% CI 0.24 to 0.8).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with bloodstream infections caused by Enterobacterales who achieved clinical stability by day 5, early oral switch was equivalent to continued IV therapy with respect to clinical cure at test of cure.
Reference
Emanuele Rando, Mercedes Delgado-Valverde, Josune Goikoetxea Aguirre et al. Effectiveness of oral step-down therapy and early oral switch for bloodstream infections caused by Enterobacterales: a post hoc emulation trial of the SIMPLIFY trial. Int J Infect Dis. 2025 Apr 29:107917. Online ahead of print.
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