The use of procalcitonin-guided antibiotic discontinuation has shown an association with greater rates of survival and reduced antibiotic utilization in critically ill individuals, albeit with a high risk of bias and low-certainty evidence. These results were published in a systematic review in Chest. Studies supporting these findings tended to have suboptimal adherence to protocol, underscoring the need for high-quality studies with a primary outcome of mortality.
Study investigators searched databases (CENTRAL, Web of Science, Scopus, EMBASE, and PubMed) for studies on procalcitonin-guided antibiotic discontinuation and duration, as well as survival in critically ill adults. Randomized controlled trials with patients admitted to intensive care units were included. The final analysis included 5000 individuals from 16 trials. All of these trials examined mortality, 15 examined length of intensive care unit stay, 13 examined exposure and duration of antibiotics, 13 examined duration of hospitalization, and 15 included a control arm. One study designated mortality as an adequately powered primary outcome. Random effects meta-analysis was used to pool data, while study quality was estimated using the Cochrane risk of bias tool. GRADEpro was used to assess the quality of evidence.
An association was found between procalcitonin-guided discontinuation of antibiotics and reduced mortality in all 16 trials (risk ratio [RR] = 0.89 [95% CI, 0.83-0.97]; I2=0%; low certainty). In 10 trials with sepsis as a subset, there was no observable survival benefit (RR=0.94 [95% CI, 0.85-1.03]; I2=0%). Similarly, no survival benefit was observed in 9 trials without industry sponsorship (RR=0.98 [95% CI, 0.87-1.10]; I2=0%), 5 trials with high adherence to procalcitonin-guided algorithms (RR=0.93 [95% CI, 0.71-1.22]), and 8 trials with procalcitonin-guided algorithms and no C-reactive protein (RR=0.96 [95% CI, 0.87-1.06]; I2=0%). Antibiotic duration decreased a mean of 1.31 days (95% CI, -2.27 to -0.35; I2=93%; low certainty) with procalcitonin-guided antibiotic discontinuation. Just one trial showed decreased mortality (19.6% vs 25%) with procalcitonin-guided antibiotic discontinuation.
Limitations to this study included a lack of reporting on whether control groups were assigned antibiotic stewardship programs, reported adverse events in 10 of the 16 trials, a lack of blinding, a limited scope of data, and the risk for attrition, detection, performance, and selection biases.
The researchers noted that “[we] found low-certainty evidence with a high risk of bias to support [procalcitonin]-guided antibiotic discontinuation to increase survival among critically ill adults. The plausibility of this survival benefit is weakened as this occurred primarily in studies with low protocol adherence (i.e. providers frequently overruled [procalcitonin] guidance) and studies with algorithms combining [procalcitonin] with other biomarkers.” The study authors concluded that antibiotic discontinuation in critically ill adults continues to be a challenge for intensivists and administrators, and the routine use of procalcitonin as a marker for completing a therapy regimen requires ongoing evaluation for efficacy.
Pepper D, Sun J, Rhee C, et al. Procalcitonin-guided antibiotic discontinuation and mortality in critically ill adults: a systematic review and meta-analysis [published online February 14, 2019]. Chest. doi: 10.1016/j.chest.2018.12.029