Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials

Abstract

BackgroundThe clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.MethodsFor this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the “procalcitonin-guided” group) or the current standard of care (the “controls”). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.ResultsMortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient −1.19 days, 95% CI −1.73 to −0.66; p < 0.001).ConclusionProcalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2125-7) contains supplementary material, which is available to authorized users.

Biomarkers of Infection: Are They Useful in the ICU?

“…Interestingly, the mortality rate in PCT-guided patients was also significantly lower compared with the control group (21.1 vs. 23.7%, p ¼ 0.03). 54 Similar effects were also noted in subgroup analyses stratified by Sepsis-3 definition, severity of sepsis, presence of renal shock, renal failure and type of infection. These positive effects may be explained by a lower risk for antibiotic side effects with PCT-guided care.…”

Sepsis 2019: What Surgeons Need to Know

“…Procalcitonin is demonstrating promise in individualizing antibiotic use. Evidence shows that this proinflammatory biomarker safely shortens antibiotic duration in critically ill patients in the ICU [36,37], and has been demonstrated to reduce mortality [38] in these and other patients. In a recent Cochrane Review, the use of procalcitonin to guide initiation and duration of antibiotic treatment resulted in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects [39].…”

Biomarkers of Sepsis: Time for a Reappraisal

“…Changes in serum CRP levels during the first 48 h after antibiotic initiation can help evaluate the response to initial antimicrobial therapy [27]. Likewise, a PCT-based algorithm may help reduce antibiotic exposure in septic patients without compromising clinical outcomes [28,29]. However, not all studies have shown the same positive effect [30], suggesting that the effectiveness of PCT-based algorithms may depend on the physician's experience and the clinical setting.…”