SIMPLIFY (original research)
Trial question
Is structured de-escalation from an antipseudomonal β-lactam to a narrower-spectrum drug noninferior to continued antipseudomonal drugs in patients with Enterobacterales bacteremia?
Study design
Multi-center
Open label
RCT
Population
331 patients.
Inclusion criteria: patients with bacteremia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam.
Key exclusion criteria: life expectancy < 30 days; pregnancy or lactation; severe neutropenia; treatment of infection > 28 days.
Interventions
N=164 de-escalation (de-escalate to a narrower-spectrum drug).
N=167 continued antipseudomonal drugs (to continue with the empiric antipseudomonal β-lactams).
Primary outcome
Rate of clinical cure 3-5 days after end of treatment
90.2%
88.6%
90.2 %
67.7 %
45.1 %
22.6 %
0.0 %
De-escalation
Continued antipseudomonal
drugs
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in the rate of clinical cure 3-5 days after end of treatment (90.2% vs. 88.6%; ARD 1.6, 95% CI -5 to 8.2).
Secondary outcomes
No significant difference in clinical cure at day 60 (92.8% vs. 90%; ARD 2.8, 95% CI -3.4 to 9).
No significant difference in the rate of relapses until day 60 (5.9% vs. 11.3%; ARD 5.54, 95% CI -0.8 to 11.6).
No significant difference in death at day 60 (4.6% vs. 5.6%; ARD 1, 95% CI -3.9 to 5.9).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with bacteremia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam, de-escalation was noninferior to continued antipseudomonal drugs with respect to the rate of clinical cure 3-5 days after end of treatment.
Reference
Luis Eduardo López-Cortés, Mercedes Delgado-Valverde, Elisa Moreno-Mellado et al. Efficacy and safety of a structured de-escalation from antipseudomonal β-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial. Lancet Infect Dis. 2024 Apr;24(4):375-385.
Open reference URL