Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice

On the Diagnosis and Management of Viral Respiratory Infections

Acute respiratory tract infections (ARTIs), are the most common infections in man, and represent a major global health burden. Viruses, most often causing a mild and self-limiting disease, yet with substantial morbidity and high costs for society, mainly cause upper respiratory tract infections. 70% of all infections in primary care in Sweden are due to ARTIs. Lower respiratory infections on the other hand constitute the third leading cause of death worldwide, mainly in children <5 years of age in resource poor settings. Distinguishing virus from bacteria can be difficult, and often lead to an over-prescription of antibiotics. Modern molecular based diagnostic methods have increased the possibility of an etiologic diagnosis of ARTIs significantly. This thesis aims to evaluate the use of a multiplex real time PCR assay targeting 13 respiratory viruses and two bacteria, from a clinical perspective. In paper I, a retrospective study of 954 nasopharyngeal samples, the PCR assay, which is based on automated specimen extraction and multiplex amplification, is described. Detection rate was 48%. Streamlined testing and cost limitation (€ 33 per sample) along with high accuracy and prompt result delivery, is key to successful implementation of broad molecular testing. Paper II evaluates in a prospective study of 209 adults with ARTI in primary care, and 100 asymptomatic controls, the impact duration of symptoms have on detection rate. Overall positive yield was 43% in patients and 2% in controls, with a significantly higher detection rate in patients with < 6 days duration of symptoms (51%) compared to ≥ 7 days (30%, p<0.01). Having access to the PCR assay reduced antibiotic prescription rates by 50%, in a prospective study (paper III) of 426 adults with ARTI. Patients receiving a result within 48 hours were prescribed antibiotics in 6,8% (n=14) compared to 15.1% (n=33, p<0.01) in the delayed result group. The diagnostic yield in paper IV, a retrospective study of 8753 patients of all ages during 36 consecutive months, was significantly higher during winter (54.7%) than in summer (31.1%, p<0.001), and in children (61.5%) compared with adults (30.5%, p<0.001). Rhinovirus was the most frequently found virus (32.5%), independent of season, and displayed a high genetic variability across seasons. The findings of this thesis support the implementation of similar methods in routine clinical care