Procalcitonin-guided antibiotic therapy in critically ill adults: a meta-analysis.
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ABSTRACT: Background
As a novel biomarker of inflammation, procalcitonin (PCT) has proven useful to guide antibiotic therapy in intensive care unit (ICU). However, there are controversial on mortality. The aim of this study was to evaluate the utility of PCT-guided antibiotic therapy in critically ill adults and determine whether studies are sufficient.Methods
A systematic search in PubMed, Embase and Cochrane was performed. We included only randomized controlled trials which compared the safety and efficacy between PCT-guided or standard antibiotic therapy groups in ICU adults. Trial sequential analysis and GARDE approach were performed.Results
Fifteen studies met our criteria for inclusion finally, with a cumulative number of 5486 ICU patients. There was no difference in 28-day mortality between two compared groups (P = 0.626), but significant decreases were observed in the duration of antibiotic therapy for the first episode of infection (P < 0.001) and length of hospitalization (P = 0.049). No significant deference was found in secondary endpoints except total duration of antibiotic therapy (P < 0.001). TSA revealed that the pooled sample sizes of 28-day mortality and the duration of antibiotic therapy for the first episode of infection exceeded the estimated required information size, but not the length of hospitalization.Conclusions
PCT-guided therapy is a better and safer algorithm to be applied into ICU patients, which appears no effect on 28-day mortality while performing preferable utility in reducing the duration of antibiotic therapy for the first episode of infection. More studies on these endpoints were not recommended.
SUBMITTER: Zhang T
PROVIDER: S-EPMC5525369 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Procalcitonin-guided antibiotic therapy in critically ill adults: a meta-analysis.
Zhang Tao T Wang Yan Y Yang Qianting Q Dong Yalin Y
BMC infectious diseases 20170724 1
<h4>Background</h4>As a novel biomarker of inflammation, procalcitonin (PCT) has proven useful to guide antibiotic therapy in intensive care unit (ICU). However, there are controversial on mortality. The aim of this study was to evaluate the utility of PCT-guided antibiotic therapy in critically ill adults and determine whether studies are sufficient.<h4>Methods</h4>A systematic search in PubMed, Embase and Cochrane was performed. We included only randomized controlled trials which compared the ...[more]
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Project description:BackgroundProcalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain.MethodsWe searched PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials (RCTs) of PCT-guided antibiotic discontinuation in critically ill adults reporting survival or antibiotic duration. Searches were conducted without language restrictions from inception to July 23, 2018. Two reviewers independently conducted all review stages; another adjudicated differences. Data were pooled using random-effects meta-analysis. Study quality was assessed with the Cochrane risk of bias tool, and evidence was graded using GRADEpro.ResultsAmong critically ill adults (5,158 randomized; 5,000 analyzed), PCT-guided antibiotic discontinuation was associated with decreased mortality (16 RCTs; risk ratio [RR], 0.89; 95% CI, 0.83-0.97; I2 = 0%; low certainty). Death was the primary outcome in only one study and a survival benefit was not observed in the subset specified as sepsis (10 RCTs; RR, 0.94; 95% CI, 0.85-1.03; I2 = 0%), those without industry sponsorship (nine RCTs; RR, 0.98; 95% CI, 0.87-1.10; I2 = 0%), high PCT-guided algorithm adherence (five RCTs; RR, 0.93; 95% CI, 0.71-1.22; I2 = 0%), and PCT-guided algorithms without C-reactive protein (eight RCTs; RR, 0.96; 95% CI, 0.87-1.06; I2 = 0%). PCT-guided antibiotic discontinuation decreased antibiotic duration (mean difference, 1.31 days; 95% CI, -2.27 to -0.35; I2 = 93%) (low certainty).ConclusionsOur findings of increased survival and decreased antibiotic utilization associated with PCT-guided antibiotic discontinuation represent low-certainty evidence with a high risk of bias. This relationship was primarily observed in studies without high protocol adherence and in studies with algorithms combining PCT and C-reactive protein. Properly designed studies with mortality as the primary outcome are needed to address this question.Trial registryInternational Prospective Register of Systematic Reviews (PROSPERO); No.: CRD42016049715; URL: http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016049715.
| S-EPMC6607427 | biostudies-literature
Project description:BackgroundSerum procalcitonin (PCT) concentration is used to guide antibiotic decisions in choice, timing, and duration of anti-infection therapy to avoid antibiotic overuse. Thus, we performed a systematic review and meta-analysis to seek evidence of different PCT-guided antimicrobial strategies for critically ill patients in terms of predefined clinical outcomes.MethodsWe searched for relevant studies in PubMed, Embase, Web of Knowledge, and the Cochrane Library up to 25 February 2017. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in adult ICU patients managed with a PCT-guided algorithm or according to standard care. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI).Data synthesisWe included 13 trials enrolling 5136 patients. These studies used PCT in three clinical strategies: initiation, discontinuation, or combination of antibiotic initiation and discontinuation strategies. Pooled analysis showed a PCT-guided antibiotic discontinuation strategy had fewer total days with antibiotics (MD - 1.66 days; 95% CI - 2.36 to - 0.96 days), longer antibiotic-free days (MD 2.26 days; 95% CI 1.40-3.12 days), and lower short-term mortality (RR 0.87; 95% CI 0.76-0.98), without adversely affecting other outcomes. Only few studies reported data on other PCT-guided strategies for antibiotic therapies, and the pooled results showed no benefit in the predefined outcomes.ConclusionsOur meta-analysis produced evidence that among all the PCT-based strategies, only using PCT for antibiotic discontinuation can reduce both antibiotic exposure and short-term mortality in a critical care setting.
| S-EPMC5700008 | biostudies-literature
Project description:BackgroundThe benefit of a procalcitonin (PCT)-guided antibiotic strategy in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains uncertain.ObjectivesThis updated meta-analysis was performed to reevaluate the therapeutic potential of PCT-guided antibiotic therapy in AECOPD.Data sourcesWe 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.ResultsEight 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 findingsA PCT-guided antibiotic strategy is associated with fewer antibiotic prescriptions, and has similar efficacy and safety compared with standard antibiotic therapy in AECOPD patients.
| S-EPMC6708820 | biostudies-literature
Project description:Unnecessary antibiotic regimens in the intensive care unit (ICU) are associated with adverse patient outcomes and antimicrobial resistance. Bacterial infections (BI) are both common and deadly in ICUs, and as a result, patients with a suspected BI are routinely started on broad-spectrum antibiotics prior to having confirmatory microbiologic culture results or when an occult BI is suspected, a practice known as empiric antibiotic therapy (EAT). However, EAT guidelines lack consensus and existing methods to quantify patient-level BI risk rely largely on clinical judgement and inaccurate biomarkers or expensive diagnostic tests. As a consequence, patients with low risk of BI often are continued on EAT, exposing them to unnecessary side effects. Augmenting current intuition-based practices with data-driven predictions of BI risk could help inform clinical decisions to shorten the duration of unnecessary EAT and improve patient outcomes. We propose a novel framework to identify ICU patients with low risk of BI as candidates for earlier EAT discontinuation. For this study, patients suspected of having a community-acquired BI were identified in the Medical Information Mart for Intensive Care III (MIMIC-III) dataset and categorized based on microbiologic culture results and EAT duration. Using structured longitudinal data collected up to 24-, 48-, and 72-hours after starting EAT, our best models identified patients at low risk of BI with AUROCs up to 0.8 and negative predictive values >93%. Overall, these results demonstrate the feasibility of forecasting BI risk in a critical care setting using patient features found in the electronic health record and call for more extensive research in this promising, yet relatively understudied, area.
| S-EPMC7530142 | biostudies-literature
Project description:BackgroundAppropriate antibiotic (AB) therapy remains a challenge in the intensive care unit (ICU). Procalcitonin (PCT)-guided AB stewardship could help optimize AB treatment and decrease AB-related adverse effects, but firm evidence is still lacking. Our aim was to compare the effects of PCT-guided AB therapy with standard of care (SOC) in critically ill patients.MethodsWe searched databases CENTRAL, Embase and Medline. We included randomized controlled trials (RCTs) comparing PCT-guided AB therapy (PCT group) with SOC reporting on length of AB therapy, mortality, recurrent and secondary infection, ICU length of stay (LOS), hospital LOS or healthcare costs. Due to recent changes in sepsis definitions, subgroup analyses were performed in studies applying the Sepsis-3 definition. In the statistical analysis, a random-effects model was used to pool effect sizes.ResultsWe included 26 RCTs (n = 9048 patients) in the quantitative analysis. In comparison with SOC, length of AB therapy was significantly shorter in the PCT group (MD - 1.79 days, 95% CI: -2.65, - 0.92) and was associated with a significantly lower 28-day mortality (OR 0.84, 95% CI: 0.74, 0.95). In Sepsis-3 patients, mortality benefit was more pronounced (OR 0.46 95% CI: 0.27, 0.79). Odds of recurrent infection were significantly higher in the PCT group (OR 1.36, 95% CI: 1.10, 1.68), but there was no significant difference in the odds of secondary infection (OR 0.81, 95% CI: 0.54, 1.21), ICU and hospital length of stay (MD - 0.67 days 95% CI: - 1.76, 0.41 and MD - 1.23 days, 95% CI: - 3.13, 0.67, respectively).ConclusionsPCT-guided AB therapy may be associated with reduced AB use, lower 28-day mortality but higher infection recurrence, with similar ICU and hospital length of stay. Our results render the need for better designed studies investigating the role of PCT-guided AB stewardship in critically ill patients.
| S-EPMC10576288 | biostudies-literature
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator
2015-10-24 | E-GEOD-74224 | biostudies-arrayexpress
Project description:Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying causative microorganisms, and the high prevalence of antibiotic-resistant strains. In this review, we briefly discuss the importance of early infection diagnosis, before considering in more detail some of the key issues related to antibiotic management in these patients, including controversies surrounding use of combination or monotherapy, duration of therapy, and de-escalation. Antibiotic pharmacodynamics and pharmacokinetics, notably volumes of distribution and clearance, can be altered by critical illness and can influence dosing regimens. Dosing decisions in different subgroups of patients, e.g., the obese, are also covered. We also briefly consider ventilator-associated pneumonia and the role of inhaled antibiotics. Finally, we mention antibiotics that are currently being developed and show promise for the future.
| S-EPMC4869332 | biostudies-literature
Project description:To examine the impact before and after adoption of a procalcitonin-based protocol to guide sepsis management has on antibiotic use, care costs, and outcomes of critically ill patients.DesignBefore-after study.SettingICU of an academic tertiary care center.PatientsAdults over 18 years old admitted to the ICU from January 1, 2017, to January 31, 2020.InterventionsIn this before-after study, we compared the use of medications, outcomes, and overall cost before and after the introduction of a procalcitonin-based protocol for evaluation and treatment of sepsis.Measurements and main resultsThe final study cohort consisted of 1,793 patients admitted to the ICU, 776 patients pre-procalcitonin and 1,017 patients in the post-procalcitonin period. Patients were not different in the pre-procalcitonin adoption period compared with post-procalcitonin adoption with regard to gender, age (62.0 vs 62.6), race, or comorbidities. Patients admitted during the post-procalcitonin adoption period were less likely to receive the examined broad-spectrum antibiotics (odds ratio, -0.58; CI, -0.99 to -0.17; p < 0.01) than patients during the pre-procalcitonin adoption period. The odds of inhospital death did not differ after procalcitonin adoption when compared with before (0.87; CI, 0.70-1.09; p = 0.234). Total charges for each admission were significantly less in the post-procalcitonin adoption period $3,834.99 compared with pre-procalcitonin adoption $4,429.47 (p < 0.05). Patients post-procalcitonin adoption incurred $1,127.18 per patient less in total charges (-1,127.18; CI, -2,014.74 to -239.62; p = 0.013) after controlling for relevant factors.ConclusionsIn critically ill patients in a large U.S. tertiary care hospital, the adoption of a procalcitonin-based protocol for evaluation and treatment of sepsis may be associated with decreased antibiotic use and significant cost savings, with no change in mortality.
| S-EPMC8580196 | biostudies-literature
Project description:BackgroundPneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment.AimsThis trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.MethodsIn this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549).ResultsIn the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001).ConclusionPCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.
| S-EPMC5402305 | biostudies-literature
Project description:BackgroundPneumonia is the most common hospital-acquired infection affecting patients in the intensive care unit (ICU). However, current national guidelines for the treatment of hospital-acquired pneumonia (HAP) are several years old and the diagnosis of pneumonia in mechanically ventilated patients (VAP) has been subject to considerable recent attention. The optimal duration of antibiotic therapy for HAP in the critically ill is uncertain.ObjectivesTo assess the effectiveness of short versus prolonged-course antibiotics for HAP in critically ill adults, including patients with VAP.Search methodsWe searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June 2015), MEDLINE in-process and other non-indexed citations (5 June 2015), EMBASE (2010 to June 2015), LILACS (1982 to June 2015) and Web of Science (1955 to June 2015).Selection criteriaWe considered all randomised controlled trials (RCTs) comparing a fixed 'short' duration of antibiotic therapy with a 'prolonged' course for HAP (including patients with VAP) in critically ill adults.Data collection and analysisTwo review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information.Main resultsWe identified six relevant studies involving 1088 participants. This included two new studies published after the date of our previous review (2011). There was substantial variation in participants, in the diagnostic criteria used to define an episode of pneumonia, in the interventions and in the reported outcomes. We found no evidence relating to patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, overall a short seven- or eight-day course of antibiotics compared with a prolonged 10- to 15-day course increased 28-day antibiotic-free days (two studies; N = 431; mean difference (MD) 4.02 days; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (one study; N = 110; odds ratio (OR) 0.44; 95% CI 0.21 to 0.95), without adversely affecting mortality and other recurrence outcomes. However, for cases of VAP specifically due to non-fermenting Gram-negative bacilli (NF-GNB), recurrence was greater after short-course therapy (two studies, N = 176; OR 2.18; 95% CI 1.14 to 4.16), though mortality outcomes were not significantly different. One study found that a three-day course of antibiotic therapy for patients with suspected HAP but a low Clinical Pulmonary Infection Score (CPIS) was associated with a significantly lower risk of superinfection or emergence of antimicrobial resistance, compared with standard (prolonged) course therapy.Authors' conclusionsOn the basis of a small number of studies and appreciating the lack of uniform definition of pneumonia, we conclude that for patients with VAP not due to NF-GNB a short, fixed course (seven or eight days) of antibiotic therapy appears not to increase the risk of adverse clinical outcomes, and may reduce the emergence of resistant organisms, compared with a prolonged course (10 to 15 days). However, for patients with VAP due to NF-GNB, there appears to be a higher risk of recurrence following short-course therapy. These findings do not differ from those of our previous review and are broadly consistent with current guidelines. There are few data from RCTs comparing durations of therapy in non-ventilated patients with HAP, but on the basis of a single study, short-course (three-day) therapy for HAP appears not to be associated with worse clinical outcome, and may reduce the risk of subsequent infection or the emergence of resistant organisms when there is low probability of pneumonia according to the CPIS.
| S-EPMC7025798 | biostudies-literature