Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock--a systematic review and meta-analysis.
ABSTRACT: Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.
Project description:BACKGROUND:The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS:In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS:The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6-10 days vs. 14 days; IQR, 12-21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION:PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02202941.
Project description:<h4>Background</h4>Procalcitonin is a biomarker that supports clinical decision-making on when to initiate and discontinue antibiotic therapy. Several cost (-effectiveness) analyses have been conducted on Procalcitonin-guided antibiotic stewardship, but none mainly based on US originated data.<h4>Objective</h4>To compare effectiveness and costs of a Procalcitonin-algorithm versus standard care to guide antibiotic prescription for patients hospitalized with a diagnosis of suspected sepsis or lower respiratory tract infection in the US.<h4>Methods</h4>A previously published health economic decision model was used to compare the costs and effects of Procalcitonin-guided care. The analysis considered the societal and hospital perspective with a time horizon covering the length of hospital stay. The main outcomes were total costs per patient, including treatment costs and productivity losses, the number of patients with antibiotic resistance or C.difficile infections, and costs per antibiotic day avoided.<h4>Results</h4>Procalcitonin -guided care for hospitalized patients with suspected sepsis and lower respiratory tract infection is associated with a reduction in antibiotic days, a shorter length of stay on the regular ward and the intensive care unit, shorter duration of mechanical ventilation, and fewer patients at risk for antibiotic resistant or C.difficile infection. Total costs in the Procalcitonin-group compared to standard care were reduced by 26.0% in sepsis and 17.7% in lower respiratory tract infection (total incremental costs of -$11,311 per patient and -$2,867 per patient respectively).<h4>Conclusions</h4>Using a Procalcitonin-algorithm to guide antibiotic use in sepsis and hospitalised lower respiratory tract infection patients is expected to generate cost-savings to the hospital and lower rates of antibiotic resistance and C.difficile infections.
Project description:Background: Procalcitonin (PCT) is a biomarker specific for bacterial infections versus viral or noninfectious causes. Utilizing PCT as a guide for antibiotic duration could have benefit in limiting antimicrobial overuse. Objective: The objective of this study was to analyze the effect of PCT monitoring on inpatient antibiotic duration for pneumonia and sepsis at a community hospital. Methods: This study utilized a prospective cohort design with a historical control group prior to the availability of PCT testing and a prospective intervention group after the availability of PCT testing at a community hospital. Results: A total of 102 patients (51 retrospective and 51 prospective) were included in the analysis. There was no difference in mean duration of inpatient antibiotics (6.1 ± 3.9 vs 5.4 ± 2.9 days, P = .50). Additionally, there was no difference in the average time to antibiotic de-escalation, average hospital length of stay, or intensive care unit length of stay. PCT monitoring resulted in a 41% reduction in discharge antibiotics (63% vs 37%, P = .0090) and a 2.2-day reduction in duration of overall inpatient and post-discharge antibiotics (9.5 ± 4.5 vs 7.3 ± 4.1 days, P = .013). There was no difference in mortality, relapse of infection, or 30-day readmission. Conclusion: PCT monitoring in patients with suspected pneumonia and/or sepsis in the community setting failed to show a reduction in duration of inpatient antibiotics after the introduction of PCT monitoring. However, PCT resulted in significantly fewer discharge antibiotics and overall inpatient plus post-discharge antibiotic duration, with no detrimental effect on mortality or readmission.
Project description:BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSION:Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
Project description:<h4>Introduction</h4>Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate.<h4>Methods and analysis</h4>In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission.<h4>Ethics and dissemination</h4>This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD.<h4>Trial registration number</h4>ClinicalTrials.gov: NCT04682899.
Project description:In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT?<?0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p?=?0.001) and peak PCT levels (p?<?0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p?=?0.002). No differences were seen in terms of other clinical outcomes.In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.
Project description:Unnecessary long-term use of broad-spectrum antibiotics is linked to the emergence and selection of resistant bacteria, prolonged hospitalisation and increased costs. Several clinical trials indicate that the biomarker procalcitonin (PCT) can guide antibiotic therapy. Some of these trials have shown a promising reduction in the number of antibiotic prescriptions, duration of antibiotic therapy and even length of stay in the ICU, although their size and selection criteria limit their external validity. The objectives of the Stop Antibiotics on guidance of Procalcitonin Study (SAPS) are to evaluate whether daily PCT can improve "real-life" antibiotic use in Dutch ICU's by reduction of the duration of antibiotic treatment without an increase of recurrent infections and mortality.Multicenter randomised controlled intervention trial. Powered for superiority of the primary efficacy endpoint and non-inferiority on the primary safety endpoints (non-inferiority margin is set on 8%).(1) ICU-patients aged ?18 years and (2) receiving antibiotics for a presumed or proven infection and (3) signed informed consent.(1) patients who require prolonged antibiotic therapy, (2) suffer from Mycobacterium tuberculosis, (3) cystic fibrosis, (4) viral or parasitic infections and (5) those that are severely immunocompromised or (6) moribund.The intervention consists solely of an advice to discontinue antibiotic treatment in case PCT has decreased by more than 80% of its peak level (relative stopping threshold) or decrease below a value of 0.5 ng/ml (absolute stopping threshold).The study hypothesis is that PCT-guided therapy is non-inferior to standard care based on implemented guidelines and local expertise, whilst reducing antibiotic usage. Computerised 1:1 randomisation will allocate 908 patients per arm. Arm 1: standard of care. Arm 2: procalcitonin-guided therapy. The primary efficacy endpoint is consumption of antibiotics expressed as the defined daily dosage and duration of antibiotic therapy expressed in days of therapy. This trial is designed to shorten antibiotics safely, therefore the primary safety endpoint is mortality measured at 28 day and 1 year.This will be the largest procalcitonin-guided antibiotic intervention trial in ICU setting thus far. Currently 1600 of the planned 1816 patients are randomised (November 2012). The first interim analysis has passed without any safety or futility issues.Trial registration number at www.clinicaltrials.gov: Id. Nr. NCT01139489, at www.trialregister.nl: Id.nr. NTR1861.
Project description:<b>Rationale:</b> Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.<b>Objectives:</b> To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.<b>Methods:</b> In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by <i>Clostridioides difficile</i> or multidrug-resistant organisms, or any death attributed to baseline <i>C. difficile</i> or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.<b>Measurements and Main Results:</b> The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; <i>P</i> = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; <i>P</i> = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days (<i>P</i> < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.<b>Conclusions:</b> In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).
Project description:PURPOSE:To compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU). METHODS:We conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%. RESULTS:A total of 302 patients were randomized into the PCT (n?=?151) and control (n?=?151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI -?0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n?=?119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p?=?0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2?±?6.5 days in the PCT group vs. 5.4?±?4.4 days in the control group, p?=?0.85 and 7.9?±?8 days in the PCT group vs. 7.7?±?5.7 days in the control group, p?=?0.75, respectively). CONCLUSION:The PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.
Project description:BACKGROUND:The benefit of a procalcitonin (PCT)-guided antibiotic strategy in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains uncertain. OBJECTIVES:This updated meta-analysis was performed to reevaluate the therapeutic potential of PCT-guided antibiotic therapy in AECOPD. DATA SOURCES:We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov up to February 2019 to identify randomized controlled trials (RCTs) investigating the role of PCT-guided antibiotic strategies in treating adult patients with AECOPD. Relative risk (RR) or mean differences (MD) with accompanying 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS:Eight RCTs with a total of 1376 participants were included. The results suggested that a PCT-guided antibiotic strategy reduced antibiotic prescriptions (RR: 0.55; 95% CI: 0.39-0.76; P = .0003). However, antibiotic exposure duration (MD: -1.34; 95% CI: -2.83-0.16; P = .08), antibiotic use after discharge (RR: 1.61; 95% CI: 0.61-4.23; P = .34), clinical success (RR: 1.02; 95% CI: 0.96-1.08; P = .47), all-cause mortality (RR: 1.05; 95% CI: 0.72-1.55; P = .79), exacerbation at follow-up (RR: 0.97; 95% CI: 0.80-1.18; P = .78), readmission at follow-up (RR: 1.12; 95% CI: 0.82-1.53; P = .49), length of hospital stay (MD: -0.36; 95% CI: -1.36-0.64; P = .48), and adverse events (RR: 1.33; 95% CI: 0.79-2.23; P = .28) were similar in both groups. IMPLICATIONS OF KEY FINDINGS:A PCT-guided antibiotic strategy is associated with fewer antibiotic prescriptions, and has similar efficacy and safety compared with standard antibiotic therapy in AECOPD patients.