Cost-effectiveness analysis of procalcitonin and lung ultrasonography guided antibiotic prescriptions in primary care.

Antimicrobial resistance comes with high morbidity and mortality burden, and ultimately high impact on healthcare and social costs. Efficient strategies are needed to limit antibiotic overuse. This paper investigates the cost-effectiveness of testing patients with lower respiratory tract infection with procalcitonin, either at the point-of-care only or combined with lung ultrasonography. These diagnostic tools help detect the presence of bacterial pneumonia, guiding prescription decisions. The clinical responses of these strategies were studied in the primary care setting. Evidence is needed on their cost-effectiveness. We used data from a cluster-randomized bi-centric clinical trial conducted in Switzerland and estimated patient-level costs using data on resource use to which we applied Swiss tariffs. Combining the incremental costs of the two strategies and the reduction in the 28-days antibiotic prescription rate (APR) compared to usual care, we calculated Incremental Cost-Effectiveness Ratios (ICER). We also used the Cost-Effectiveness Acceptability Curve as an analytical decision-making tool. The robustness of the findings is ensured by Probabilistic Sensitivity Analysis and scenario analysis. In the base case scenario, the ICER compared to usual care is $2.3 per percentage point (pp) reduction in APR for the procalcitonin group, and $4.4 for procalcitonin-ultrasound combined. Furthermore, we found that for a willingness to pay per patient of more than $2 per pp reduction in the APR, procalcitonin is the strategy with the highest probability to be cost-effective. Our findings suggest that testing patients with respiratory symptoms with procalcitonin to guide antibiotic prescription in the primary care setting represents good value for money.

Patient Stratification for Antibiotic Prescriptions Based on the Bound-Free Phase Detection Immunoassay of C-Reactive Protein in Serum Samples.

C-reactive protein is a well-studied host response biomarker, whose diagnostic performance depends on its accurate classification into concentration zones defined by clinical scenario-specific cutoff values. We validated a newly developed, bead-based, bound-free phase detection immunoassay (BFPD-IA) versus a commercial CE-IVD enzyme-linked immunosorbent assay (ELISA) kit and a commercial CE-IVD immunoturbidimetric assay (ITA) kit. The latter was performed on a fully automated DPC Konelab 60i clinical analyzer used in routine diagnosis. We classified 53 samples into concentration zones derived from four different sets of cutoff values that are related to antibiotic prescription scenarios in the case of respiratory tract infections. The agreements between the methods were ELISA/ITA at 87.7%, ELISA/BFPD-IA at 87.3%, and ITA/-BFPD-IA at 93.9%, reaching 98-99% in all cases when considering the calculated relative combined uncertainty of the single measurement of each sample. In a subgroup of 37 samples, which were analyzed for absolute concentration quantification, the scatter plot slopes' correlations were as follows: ELISA/ITA 1.15, R2 = 0.97; BFPD-IA/ELISA 1.12, R2 = 0.95; BFPD-IA/ITA 0.95, R2 = 0.93. These very good performances and the agreement between BFPD-IA and ITA (routine diagnostic), combined with BFPD-IA's functional advantages over ITA (and ELISA)-such as quick time to result (~20 min), reduced consumed reagents (only one assay buffer and no washing), few and easy steps, and compatibility with nucleic-acid-amplification instruments-render it a potential approach for a reliable, cost-efficient, evidence-based point-of-care diagnostic test for guiding antibiotic prescriptions.

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs.

Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

BACKGROUND: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. AIM: To explore the factors associated with the overruling of initial procalcitonin guidance. DESIGN AND SETTING: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. METHOD: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. RESULTS: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03-3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32-9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34-23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18-4.37); and the GP's number of years of experience (aOR per year 1.05, 1.01-1.09). CONCLUSIONS: Overruling of procalcitonin guidance was associated with GPs' socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.