The 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. For 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. Mortality 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). Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.

Procalcitonin (PCT) testing can help in safely reducing antibiotic treatment duration in intensive care patients with sepsis. However, the cost-effectiveness of such PCT guidance is not yet known. A trial-based analysis was performed to estimate the cost-effectiveness of PCT guidance compared with standard of care (without PCT guidance). Patient-level data were used from the SAPS trial in which 1546 patients were randomised. This trial was performed in the Netherlands, which is a country with, on average, low antibiotic use and a short duration of hospital stay. As quality of life among sepsis survivors was not measured during the SAPS, this was derived from a Dutch follow-up study. Outcome measures were (1) incremental direct hospital cost and (2) incremental cost per quality-adjusted life year (QALY) gained from a healthcare perspective over a one-year time horizon. Uncertainty in outcomes was assessed with bootstrapping. Mean in-hospital costs were €46,081/patient in the PCT group compared with €46,146/patient with standard of care (i.e. − €65 (95% CI − €6314 to €6107); − 0.1%). The duration of the first course of antibiotic treatment was lower in the PCT group with 6.9 vs. 8.2 days (i.e. − 1.2 days (95% CI − 1.9 to − 0.4), − 14.8%). This was accompanied by lower in-hospital mortality of 21.8% vs. 29.8% (absolute decrease 7.9% (95% CI − 13.9% to − 1.8%), relative decrease 26.6%), resulting in an increase in mean QALYs/patient from 0.47 to 0.52 (i.e. + 0.05 (95% CI 0.00 to 0.10); + 10.1%). However, owing to high costs among sepsis survivors, healthcare costs over a one-year time horizon were €73,665/patient in the PCT group compared with €70,961/patient with standard of care (i.e. + €2704 (95% CI − €4495 to €10,005), + 3.8%), resulting in an incremental cost-effectiveness ratio of €57,402/QALY gained. Within this time frame, the probability of PCT guidance being cost-effective was 64% at a willingness-to-pay threshold of €80,000/QALY. Although the impact of PCT guidance on total healthcare-related costs during the initial hospitalisation episode is likely negligible, the lower in-hospital mortality may lead to a non-significant increase in costs over a one-year time horizon. However, since uncertainty remains, it is recommended to investigate the long-term cost-effectiveness of PCT guidance, from a societal perspective, in different countries and settings.

Background: New Sepsis-3 definitions facilitate early recognition of patients with sepsis. In this study we investigated whether a single initial determination of procalcitonin (PCT) or C-reactive protein (CRP) in plasma can predict proven sepsis in Sepsis-3 criteria-positive critically ill patients. We also investigated whether a decline in serial PCT or CRP can predict outcome in 28-day mortality. Methods: Patients, ≥18 years of age, at the intensive care unit with a suspected infection, a Sequential Organ Failure Assessment (SOFA) score of ≥2 points, and an index test PCT and CRP at admission were selected from a prospectively collected cohort. PCT and CRP were studied retrospectively with the Mann–Whitney U-test and ROC analysis. Results: In total, 157 patients were selected; 63 of the 157 had proven sepsis, and sepsis could not be detected in 94 of the 157. Neither a single PCT nor CRP at admission was able to discriminate proven sepsis from nonproven sepsis (PCT, 1.8 μg/L and 1.5 μg/L, respectively, P = 0.25; CRP, 198 mg/L and 186 mg/L, respectively, P = 0.53). Area under the curve for both PCT and CRP for detecting proven sepsis was low (0.55 and 0.53). Furthermore, neither a decline from baseline to day 5 PCT nor CRP could predict 28-day mortality (PCT, 50% vs 46%, P = 0.83; CRP, 30% vs 40%, P = 0.51). Conclusion: PCT and CRP at admission were not able to discern patients with proven sepsis in Sepsis-3 criteria-positive critically ill patients. A decline of PCT and CRP in 5 days was not able to predict 28-day mortality.

Background and Objectives: The aim of this study was to investigate the association between obesity and 28-day mortality, duration of invasive mechanical ventilation and length of stay at the Intensive Care Unit (ICU) and hospital in patients admitted to the ICU for SARS-CoV-2 pneumonia. Materials and Methods: This was a retrospective observational cohort study in patients admitted to the ICU for SARS-CoV-2 pneumonia, in a single Dutch center. The association between obesity (body mass index > 30 kg/m²) and 28-day mortality, duration of invasive mechanical ventilation and length of ICU and hospital stay was investigated. Results: In 121 critically ill patients, pneumonia due to SARS-CoV-2 was confirmed by RT-PCR. Forty-eight patients had obesity (33.5%). The 28-day all-cause mortality was 28.1%. Patients with obesity had no significant difference in 28-day survival in Kaplan–Meier curves (log rank p 0.545) compared with patients without obesity. Obesity made no significant contribution in a multivariate Cox regression model for prediction of 28-day mortality (p = 0.124), but age and the Sequential Organ Failure Assessment (SOFA) score were significant independent factors (p < 0.001 and 0.002, respectively). No statistically significant correlation was observed between obesity and duration of invasive mechanical ventilation and length of ICU and hospital stay. Conclusion: One-third of the patients admitted to the ICU for SARS-CoV-2 pneumonia had obesity. The present study showed no relationship between obesity and 28-day mortality, duration of invasive mechanical ventilation, ICU and hospital length of stay. Further studies are needed to substantiate these findings.