Effect of procalcitonin-based guidelines compared with standard guidelines on antibiotic use in lower respiratory tract infections: the randomized-controlled multicenter ProHOSP trial
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ABSTRACT:
SUBMITTER: Schuetz P
PROVIDER: S-EPMC4084272 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundOveruse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns.MethodsThe Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection.DiscussionWe describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation.Trial registrationClinicalTrials.gov NCT02130986 . Registered May 1, 2014.
| S-EPMC5576372 | biostudies-literature
Project description:Background: Distinguishing between bacterial and viral lower respiratory tract infections (LRTI) in hospitalized patients remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods: We performed whole blood transcriptional analysis in a cohort of 118 adult patients (median [IQR] age, 61 [50-76] years) hospitalized with bacterial, viral or viral-bacterial LRTI, and 40 age-matched healthy controls (60 [46-70] years). We applied class comparisons, modular analysis and class prediction algorithms to identify distinct biosignatures for bacterial and viral LRTI, which were validated in an independent group of patients. Results: Patients were classified as bacterial (B, n=22), viral (V, n=71) and bacterial-viral LRTI (BV, n=25) based on comprehensive microbiologic testing. Compared with healthy controls statistical group comparisons (p<0.01; with multiple test corrections) identified 3,376 differentially expressed genes in patients with B-LRTI; 2,391 in V-LRTI, and 2,628 in BV-LRTI. Independent of etiologic pathogen, patients with LRTI demonstrated overexpression of innate immunity and underexpression of adaptive immunity genes. Patients with B-LRTI showed significant overexpression of inflammation (B>BV>V) and neutrophils (B>BV>V) while those with V-LRTI displayed significantly greater overexpression of interferon genes (V>BV>B). The K-Nearest Neighbors (K-NN) algorithm identified 10 classifier genes that discriminated patients with bacterial vs viral LRTI with 97% [95%CI: 84-100] sensitivity and 92% [77-98] specificity. In comparison, procalcitonin classified bacterial vs viral LRTI with 38% [18-62] sensitivity and 91% [76-98] specificity. Conclusions: Transcriptional profiling can be used as a helpful tool for the diagnosis of adults hospitalized with LRTI. 158 samples, no replicates; bacterial LRTI n=22, viral LRTI n=71, bacterial-viral coinfections n=25, and healthy controls n=40
2015-09-14 | E-GEOD-60244 | biostudies-arrayexpress
Project description:Background: Distinguishing between bacterial and viral lower respiratory tract infections (LRTI) in hospitalized patients remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods: We performed whole blood transcriptional analysis in a cohort of 118 adult patients (median [IQR] age, 61 [50-76] years) hospitalized with bacterial, viral or viral-bacterial LRTI, and 40 age-matched healthy controls (60 [46-70] years). We applied class comparisons, modular analysis and class prediction algorithms to identify distinct biosignatures for bacterial and viral LRTI, which were validated in an independent group of patients. Results: Patients were classified as bacterial (B, n=22), viral (V, n=71) and bacterial-viral LRTI (BV, n=25) based on comprehensive microbiologic testing. Compared with healthy controls statistical group comparisons (p<0.01; with multiple test corrections) identified 3,376 differentially expressed genes in patients with B-LRTI; 2,391 in V-LRTI, and 2,628 in BV-LRTI. Independent of etiologic pathogen, patients with LRTI demonstrated overexpression of innate immunity and underexpression of adaptive immunity genes. Patients with B-LRTI showed significant overexpression of inflammation (B>BV>V) and neutrophils (B>BV>V) while those with V-LRTI displayed significantly greater overexpression of interferon genes (V>BV>B). The K-Nearest Neighbors (K-NN) algorithm identified 10 classifier genes that discriminated patients with bacterial vs viral LRTI with 97% [95%CI: 84-100] sensitivity and 92% [77-98] specificity. In comparison, procalcitonin classified bacterial vs viral LRTI with 38% [18-62] sensitivity and 91% [76-98] specificity. Conclusions: Transcriptional profiling can be used as a helpful tool for the diagnosis of adults hospitalized with LRTI.
2015-09-14 | GSE60244 | GEO
Project description:BackgroundEuropean trials using procalcitonin (PCT)-guided antibiotic therapy for patients with lower respiratory tract infections (LRTIs) have demonstrated significant reductions in antibiotic use without increasing adverse outcomes. Few studies have examined PCT for LRTIs in the United States.MethodsIn this study, we evaluated whether a PCT algorithm would reduce antibiotic exposure in patients with LRTI in a US hospital. We conducted a controlled pre-post trial comparing an intervention group of PCT-guided antibiotic therapy to a control group of usual care. Consecutive patients admitted to medicine services and receiving antibiotics for LRTI were enrolled in the intervention. Providers were encouraged to discontinue antibiotics according to a PCT algorithm. Control patients were similar patients admitted before the intervention.ResultsThe primary endpoint was median antibiotic duration. Overall adverse outcomes at 30 days comprised death, transfer to an intensive care unit, antibiotic side effects, Clostridium difficile infection, disease-specific complications, and post-discharge antibiotic prescription for LRTI. One hundred seventy-four intervention patients and 200 controls were enrolled. Providers complied with the PCT algorithm in 75% of encounters. Procalcitonin-guided therapy reduced median antibiotic duration for pneumonia from 7 days to 6 (P = .045) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) from 4 days to 3 (P = .01). There was no difference in the rate of adverse outcomes in the PCT and control groups.ConclusionsA PCT-guided algorithm safely reduced the duration of antibiotics for treating LRTI. Utilization of a PCT algorithm may aid antibiotic stewardship efforts.This clinical trial was a single-center, controlled, pre-post study of PCT-guided antibiotic therapy for LRTI. The intervention (incorporation of PCT-guided algorithms) started on April 1, 2017: the preintervention (control group) comprised patients admitted from November 1, 2016 to April 16, 2017, and the postintervention group comprised patients admitted from April 17, 2017 to November 29, 2017 (Supplementary Figure 1). The study comprised patients admitted to the internal medicine services to a medical ward, the Medical Intensive Care Unit (MICU), the Cardiac Intensive Care Unit (CICU), or the Progressive Care Unit (PCU) "step down unit". The registration data for the trails are in the ClinicalTrials.gov database, number NCT0310910.
| S-EPMC6306569 | biostudies-literature
Project description:BackgroundRandomized controlled trials have shown that procalcitonin-guided algorithms can reduce antibiotic duration for lower respiratory tract infections (LRTIs). The goal of this study was to compare antibiotic duration for LRTIs with and without procalcitonin testing in real-life practice.MethodsThis retrospective cohort study included all acute care hospital admissions for presumed LRTIs between 1/2018 and 12/2021 at 81 Veterans Affairs facilities with on-site procalcitonin testing. The exposure was procalcitonin testing; the primary outcome was antibiotic duration. We used 1:1 nearest-neighbor propensity score matching to estimate the difference in outcome between procalcitonin-tested and nontested patients.ResultsA total of 35 610 patients with LRTIs were included (6015 [16.9%] with procalcitonin testing; 29 595 [83.1%] without testing). In tested patients, the median number of procalcitonin levels checked (interquartile range) was 2 (1-3). The mean antibiotic duration was 10.0 days in the procalcitonin group compared with 8.3 days in nontested patients (unadjusted difference, 1.7 days; P < .0001). After propensity score matching with 3903 pairs, antibiotic duration remained greater in the procalcitonin group (9.6 days vs 9.2 days; P < .0001). In a subgroup analysis of 2241 tested patients with a procalcitonin value at the standard threshold for antibiotic discontinuation, antibiotic duration was shorter in tested vs nontested patients, with a mean difference of 0.1 days (P < .01).ConclusionsIn this retrospective propensity-matched cohort of patients with presumed LRTIs across a geographically diverse group of hospitals, patients who underwent procalcitonin testing did not have a meaningful reduction in antibiotic duration compared with those who were not tested. Poor implementation of procalcitonin testing may have undermined its effectiveness.
| S-EPMC10629903 | biostudies-literature
Project description:These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.
| S-EPMC5754344 | biostudies-literature
Project description:BackgroundThe effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.MethodsIn 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.ResultsA total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval [CI], -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% [96 patients] and 13.1% [109 patients]; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days.ConclusionsThe provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).
| S-EPMC6197800 | biostudies-literature
Project description:BackgroundDistinguishing between bacterial and viral lower respiratory tract infection (LRTI) remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI.MethodsWe performed whole blood transcriptional analysis in 118 patients (median age [interquartile range], 61 [50-76] years) hospitalized with LRTI and 40 age-matched healthy controls (median age, 60 [46-70] years). We applied class comparisons, modular analysis, and class prediction algorithms to identify and validate diagnostic biosignatures for bacterial and viral LRTI.ResultsPatients were classified as having bacterial (n = 22), viral (n = 71), or bacterial-viral LRTI (n = 25) based on comprehensive microbiologic testing. Compared with healthy controls, statistical group comparisons (P < .01; multiple-test corrections) identified 3376 differentially expressed genes in patients with bacterial LRTI, 2391 in viral LRTI, and 2628 in bacterial-viral LRTI. Patients with bacterial LRTI showed significant overexpression of inflammation and neutrophil genes (bacterial > bacterial-viral > viral), and those with viral LRTI displayed significantly greater overexpression of interferon genes (viral > bacterial-viral > bacterial). The K-nearest neighbors algorithm identified 10 classifier genes that discriminated between bacterial and viral LRTI with a 95% sensitivity (95% confidence interval, 77%-100%) and 92% specificity (77%-98%), compared with a sensitivity of 38% (18%-62%) and a specificity of 91% (76%-98%) for procalcitonin.ConclusionsTranscriptional profiling is a helpful tool for diagnosis of LRTI.
| S-EPMC4565998 | biostudies-literature
Project description:BackgroundKnowledge of key drivers for antibiotic prescribing in pediatric lower respiratory tract infection (LRTI) could support rational antibiotic use. Thus, we aimed to determine the impact of clinical and laboratory factors on antibiotic prescribing in children and adolescents with febrile LRTI.MethodsPediatric patients from the standard care control group of a randomized controlled trial (ProPAED) investigating procalcitonin guided antibiotic treatment in febrile LRTI were included in a multivariate logistic regression analysis to evaluate the impact of laboratory and clinical factors on antibiotic prescribing.ResultsThe standard care control group of the ProPAED study comprised 165 LRTI patients (median age: 2.7 years, range: 0.1-16), out of which 88 (55%) received antibiotic treatment. Factors significantly associated with antibiotic prescribing in patients with complete clinical and laboratory documentation (n = 158) were C-reactive protein (OR 5.8 for a 10-fold increase, 95%CI 2.2-14.9), white blood count beyond age-dependent reference range (OR 3.9, 95%CI 1.4-11.4), body temperature (OR 1.7 for an increase by 1°C, 95%CI 1.02-2.68), and pleuritic pain (OR 2.8, 95%CI 1.1-7.6). Dyspnea (OR 0.3, 95%CI 0.1-0.7) and wheezing (OR 0.3, 95%CI 0.13-0.95) were inversely associated with antibiotic prescribing.ConclusionLaboratory markers were strong drivers of antibiotic prescribing in children with febrile lower respiratory tract infections, in spite of their known poor prediction of antibiotic need. Building on current guidelines for antibiotic treatment in children with febrile LRTI, a reliable decision algorithm for safe antibiotic withholding considering the laboratory and clinical factors evaluated in this study has the potential to further reduce antibiotic prescribing.
| S-EPMC5619731 | biostudies-literature
Project description:Viral lower respiratory tract infection (VLRTI) is the most common cause of hospital admission among small children in high-income countries. Guidelines to identify children in need of admission are lacking in the literature. In December 2012, our hospital introduced strict guidelines for admission. This study aims to retrospectively evaluate the safety and efficacy of the guidelines. We performed a single-center retrospective administrative database search and medical record review. ICD-10 codes identified children < 24 months assessed at the emergency department for VLRTI for a 10-year period. To identify adverse events related to admission guidelines implementation, we reviewed patient records for all those discharged on primary contact followed by readmission within 14 days. During the study period, 3227 children younger than 24 months old were assessed in the ED for VLRTI. The proportion of severe adverse events among children who were discharged on their initial emergency department contact was low both before (0.3%) and after the intervention (0.5%) (p=1.0). Admission rates before vs. after the intervention were for previously healthy children > 90 days 65.3% vs. 53.3% (p<0.001); for healthy children ≤ 90 days 85% vs. 68% (p<0.001); and for high-risk comorbidities 74% vs. 71% (p=0.5).Conclusion: After implementation of admission guidelines for VLRTI, there were few adverse events and a significant reduction in admissions to the hospital from the emergency department. Our admission guidelines may be a safe and helpful tool in the assessment of children with VLRTI. What is Known: • Viral lower respiratory tract infection, including bronchiolitis, is the most common cause of hospitalization for young children in the developed world. Treatment is mainly supportive, and hospitalization should be limited to the cases in need of therapeutic intervention. • Many countries have guidelines for the management of the disease, but the decision on whom to admit for inpatient treatment is often subjective and may vary even between physicians in the same hospital. What is New: • Implementation of admission criteria for viral lower respiratory tract infection may reduce the rate of hospital admissions without increasing adverse events.
| S-EPMC8285352 | biostudies-literature