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
Pragmatic RCT (n=344) found, in those on empiric antipseudomonal β-lactams for Enterobacterales bacteraemia, de-escalation to a susceptible narrow spectrum regimen was non-inferior for clinical cure vs continued empiric therapy (90% vs 89%, diff +1.6%, 95%CI -5.0 to +8.2).
Source:
The Lancet Infectious Diseases
SPS commentary:
De-escalation options were ampicillin, trimethoprim–sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin–clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility. Non-inferiority was declared when the lower bound of the 95% confidence interval of the absolute difference in cure rate was above the –10%.
A related commentary notes the study confirms the safety of de-escalation in a population with Enterobacterales bloodstream infections, and that these results are useful for clinicians pondering whether de-escalation of broad spectrum β-lactams should be used for their patients. It concludes that with the advent of rapid diagnostic testing, it is hoped that the need for empirical antibiotics will soon decrease, and broad-spectrum antibiotics will be reserved for patients with a definitive indication.