When once is not enough--further evidence of procalcitonin-guided antibiotic stewardship.
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ABSTRACT:
SUBMITTER: Harbarth S
PROVIDER: S-EPMC2750139 | biostudies-other | 2009
REPOSITORIES: biostudies-other
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When once is not enough--further evidence of procalcitonin-guided antibiotic stewardship.
Harbarth Stephan S Albrich Werner C WC Müller Beat B
Critical care (London, England) 20090713 4
Every day, critical care physicians around the world face the same challenge of the optimal timing of antimicrobial administration: when to start and when to stop antibiotics. Duration of antibiotic therapy for sepsis is mostly based on expert opinion, but its reduction is arguably the most promising approach to decrease emergence and selection of antibiotic resistance. The study by Hochreiter and colleagues presents another piece of evidence suggesting that procalcitonin may indeed be a valuabl ...[more]
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Project description:Several controlled clinical studies have evaluated the potential of the infection biomarker procalcitonin (PCT) to improve the diagnostic work-up of patients with bacterial infections and its influence on decisions regarding antibiotic therapy. Most research has focused on lower respiratory tract infections and critically ill sepsis patients. A clinical utility for PCT has also been found for patients with urinary tract infections, postoperative infections, meningitis, and patients with acute heart failure with possible superinfection (i.e., pneumonia). In these indications, PCT levels measured on hospital admission were found to substantially reduce the initiation of antibiotic treatment in low-risk situations (i.e., bronchitis, chronic obstructive pulmonary disease exacerbation). For more severe infections (i.e., pneumonia, sepsis), antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapy. Importantly, these strategies appear to be safe without increasing the risk for mortality, recurrent infections, or treatment failures. PCT kinetics also proved to have prognostic value correlating with disease severity (i.e., pancreatitis, abdominal infection) and resolution of illness (i.e., sepsis). Although promising findings have been published in these different types of infections, there are a number of limitations regarding PCT, including suboptimal sensitivity and/or specificity, which makes a careful interpretation of PCT in the clinical context mandatory. This narrative review aims to update clinicians on the strengths and limitations of PCT for patient management, focusing on research conducted within the last 4 years.
| S-EPMC5259962 | biostudies-literature
Project description:Delayed pathogen identification and nonspecific clinical findings make definitive decisions regarding antibiotics challenging. The stimuli of bacterial toxins and inflammation make procalcitonin (PCT) unique in its ability to differentiate bacterial infection from other causes of inflammation, and thus it is useful for antibiotic management. The objective of our study was to evaluate the impact of a PCT algorithm (PCT-A) on current practice.A single-center, retrospective cohort study was conducted to evaluate the impact of adding PCT-A to stewardship practices. Data from 4 years prior to and after PCT-A implementation were compared in critical and acute care patients of all ages receiving parenteral antibiotics for a DRG coded for infection. A baseline PCT was obtained on admission in patients with suspected bacterial infection. Serial PCT measurements were repeated daily to evaluate effectiveness of therapy. Outcomes of interest were antibiotic exposure, hospital mortality, 30-day readmission, Clostridium difficile infection (CDI), and adverse drug events during hospitalization.A total of 985 patients (pre-PCT-A group) were compared with 1167 patients (post-PCT-A group). Antimicrobial stewardship alone (pre-PCT-A) resulted in a median days of therapy (DOT) of 17 (interquartile range [IQR], 8.5-22.5) vs 9.0 (IQR, 6.5-12) in the post-PCT-A group (P < .0001). Secondary outcomes were also significantly reduced in the post-PCT-A group.The addition of PCT in a facility with an established stewardship program resulted in a significant reduction in antibiotic exposure and adverse outcomes. PCT may improve antibiotic management when diagnostic clarity and resolution of infection are lacking.
| S-EPMC5695623 | biostudies-literature
Project description:BackgroundProcalcitonin is a biomarker that may be able to identify patients with COVID-19 pneumonia who do not require antimicrobials for bacterial respiratory tract co-infections.ObjectivesTo evaluate the safety and effectiveness of a procalcitonin-guided algorithm in rationalizing empirical antimicrobial prescriptions in non-critically ill patients with COVID-19 pneumonia.MethodsRetrospective, single-site, cohort study in adults hospitalized with confirmed or suspected COVID-19 pneumonia and receiving empirical antimicrobials for potential bacterial respiratory tract co-infection. Regression models were used to compare the following outcomes in patients with and without procalcitonin testing within 72 h of starting antimicrobials: antimicrobial consumption (DDD); antimicrobial duration; a composite safety outcome of death, admission to HDU/ICU or readmission to hospital within 30 days; and length of admission. Procalcitonin levels of ≤0.25 ng/L were interpreted as negatively predictive of bacterial co-infection. Effects were expressed as ratios of means (ROM) or prevalence ratios (PR) accordingly.Results259 patients were included in the final analysis. Antimicrobial use was lower in patients who had procalcitonin measured within 72 h of starting antimicrobials: mean antimicrobial duration 4.4 versus 5.4 days, adjusted ROM 0.7 (95% CI 0.6-0.9); mean antimicrobial consumption 6.8 versus 8.4 DDD, adjusted ROM 0.7 (95% CI 0.6-0.8). Both groups had similar composite safety outcomes (adjusted PR 0.9; 95% CI 0.6-1.3) and lengths of admission (adjusted ROM 1.3; 95% CI 0.9-1.6).ConclusionsA procalcitonin-guided algorithm may allow for the safe reduction of antimicrobial usage in hospitalized non-critically ill patients with COVID-19 pneumonia.
| S-EPMC8378277 | biostudies-literature
Project description:BackgroundAs 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.MethodsA 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.ResultsFifteen 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.ConclusionsPCT-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.
| S-EPMC5525369 | 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:Serum 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.We 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).We 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.Our 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-other
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.
| S-EPMC5986690 | biostudies-other
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: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:Procalcitonin levels rise in response to systemic inflammation, especially of bacterial origin. Multiple randomized controlled trials have demonstrated that procalcitonin-based algorithms can safely reduce antibiotic use in 2 clinical scenarios. First, in stable, low-risk patients with respiratory infections, procalcitonin levels of <0.25 µg/L can guide the decision to withhold antibiotics or stop therapy early. Second, in critically ill patients with suspected sepsis, clinicians should not initially withhold antibiotics, but procalcitonin levels of <0.5 µg/L or levels that decrease by ?80% from peak can guide discontinuation once patients stabilize. The recent stop antibiotics on procalcitonin guidance study (SAPS), the largest procalcitonin trial to date, demonstrated reduction in both antibiotic exposure and mortality in critically ill patients. Although procalcitonin is ready for routine use, future research should examine optimal strategies for implementation in hospitals, its real-world impact on clinical outcomes and costs, its applicability to immunocompromised patients, and the generalizability of trials to the US population.
| S-EPMC5414114 | biostudies-other