Claudine Falconnier

Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

CONTEXT In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs). OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes. DESIGN, SETTING, AND PATIENTS A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008. INTERVENTION Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based. MAIN OUTCOME MEASURES Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics. RESULTS The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%). CONCLUSION In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN95122877.

Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections

IntroductionMeasurement of prohormones representing different pathophysiological pathways could enhance risk stratification in patients with community-acquired pneumonia (CAP) and other lower respiratory tract infections (LRTI).MethodsWe assessed clinical parameters and five biomarkers, the precursor levels of adrenomedullin (ADM), endothelin-1 (ET1), atrial-natriuretic peptide (ANP), anti-diuretic hormone (copeptin), and procalcitonin in patients with LRTI and CAP enrolled in the multicenter ProHOSP study. We compared the prognostic accuracy of these biomarkers with the pneumonia severity index (PSI) and CURB65 (Confusion, Urea, Respiratory rate, Blood pressure, Age 65) score to predict serious complications defined as death, ICU admission and disease-specific complications using receiver operating curves (ROC) and reclassification methods.ResultsDuring the 30 days of follow-up, 134 serious complications occurred in 925 (14.5%) patients with CAP. Both PSI and CURB65 overestimated the observed mortality (X2 goodness of fit test: P = 0.003 and 0.01). ProADM or proET1 alone had stronger discriminatory powers than the PSI or CURB65 score or any of either score components to predict serious complications. Adding proADM alone (or all five biomarkers jointly) to the PSI and CURB65 scores, significantly increased the area under the curve (AUC) for PSI from 0.69 to 0.75, and for CURB65 from 0.66 to 0.73 (P < 0.001, for both scores). Reclassification methods also established highly significant improvement (P < 0.001) for models with biomarkers if clinical covariates were more flexibly adjusted for. The developed prediction models with biomarkers extrapolated well if evaluated in 434 patients with non-CAP LRTIs.ConclusionsFive biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI. Intervention studies are warranted to show whether an improved risk prognostication with biomarkers translates into a better clinical management and superior allocation of health care resources.Trial RegistrationNCT00350987.

Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: Results from the randomized ProHOSP trial

BACKGROUND/OBJECTIVES We sought to determine whether exclusion of infection and antibiotic stewardship with the infection biomarker procalcitonin improves outcomes in congestive heart failure (CHF) patients presenting to emergency departments with respiratory symptoms and suspicion of respiratory infection. METHODS We performed a secondary analysis of patients with a past medical history of CHF formerly included in a Swiss multicenter randomized-controlled trial. The trial compared antibiotic stewardship according to a procalcitonin algorithm or state-of-the-art guidelines (controls). The primary endpoint was a 30-day adverse outcome (death, intensive care unit admission); the secondary endpoints included a 30-day antibiotic exposure. RESULTS In the 110/233 analyzed patients (47.2%) with low initial procalcitonin (<0.25 μg/L), suggesting the absence of systemic bacterial infection, those randomized to procalcitonin guidance (n=50) had a significantly lower adverse outcome rate compared to controls (n=60): 4% vs. 20% (absolute difference -16.0%, 95% confidence interval (CI) -28.4% to -3.6%, P=0.01), and significantly reduced antibiotic exposure [days] (mean 3.7 ± 4.0 vs. 6.5 ± 4.4, difference -2.8 [95% CI, -4.4 to -1.2], P<0.01). When initial procalcitonin was ≥0.25 μg/L, procalcitonin-guided patients had significantly reduced antibiotic exposure due to early stop of therapy without any difference in adverse outcomes (25.8% vs. 24.6%, difference [95% CI] 1.2% [-14.5% to 16.9%, P=0.88]). CONCLUSIONS CHF patients presenting to the emergency department with respiratory symptoms and suspicion for respiratory infection had decreased antibiotic exposure and improved outcomes when procalcitonin measurement was used to exclude bacterial infection and guide antibiotic treatment. These data provide further evidence for the potential harmful effects of antibiotic / fluid treatment when used instead of diuretics and heart failure medication in clinically symptomatic CHF patients without underlying infection.

Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study

Prediction of long‐term outcomes in patients with community‐acquired pneumonia (CAP) is incompletely understood. We investigated the value of clinical risk scores [pneumonia severity index (PSI) and CURB‐65] (Confusion, Urea, Respiratory rate, Blood Pressure, Age >65 years) and blood biomarkers of different physiopathological pathways in predicting long‐term survival in a well‐characterized cohort of patients with CAP enrolled in an antibiotic stewardship trial.

Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type

Abstract Long-term outcome prediction in COPD is challenging. We conducted a prospective 5–7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th–75th percentile] 6.1 [5.6–6.5] years, mortality was 55% (95%CI 50%–59%). Discharge ProADM concentration was strongly associated with 5–7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2–17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701–0.789) versus 0.727 (0.681–0.772), p = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5–7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

Steps to Take to Reduce Length of Hospital Stay in Patients With Lower Respiratory Tract Infections: A Prospective Cohort Study

Background: Identification of medical and nonmedical requirements for outpatient treatment and/or early hospital discharge have potential to decrease health care costs. Method: On admission and before discharge, physicians and nurses, patients, and their relatives were interviewed about requirements over five domains (medical, nursing, organizational, and patients’ and their relatives’ preferences) for outpatient management and/or early discharge. Results: From a total of 550 included patients, 136 (24.7%) potential outpatients and 265 (48.2%) potential patients for early discharge were identified. Specific medical and nursing factors and factors related to patients and relatives were identified as being important for initial outpatient treatment and/or early discharge. Conclusion: This survey shows important requirements from the perspective of different heath care workers, patients, and relatives, which could allow initial outpatient treatment and/or early discharge of a large proportion of lower respiratory tract infection (LRTI) patients.