Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care.

BACKGROUND: Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology. A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics. We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day. METHODS: Fifty-three primary care physicians recruited 458 patients, each patient with an acute respiratory tract infection and, in the physician's opinion, in need of antibiotics. Patients were centrally randomized to either a procalcitonin-guided approach to antibiotic therapy or to a standard approach. For patients randomized to procalcitonin-guided therapy, the use of antibiotics was more or less strongly discouraged (procalcitonin level, < or =0.1 or < or =0.25 microg/L, respectively) or recommended (procalcitonin level, >0.25 microg/L). Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers. RESULTS: Adjusted for baseline characteristics, the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], -0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]). CONCLUSIONS: As an adjunct to guidelines, procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics.

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.

Patients' expectations about the benefit of antibiotic treatment: lessons from a randomised controlled trial.

BACKGROUND: Patient expectations may be an important component of a placebo effect, and yet few studies assess how patients' pre-existing expectations affect subsequent health outcomes. OBJECTIVES: To estimate the association between patients' expectations and time to cure in patients with clinically diagnosed acute bacterial rhinosinusitis. METHODS: In a randomised controlled trial, expectations about the benefit of an antibiotic therapy were measured prior to treatment with either an antibiotic or placebo. RESULTS: Of the patients asked for consent, 64% refused mostly because they either wanted or did not want to receive antibiotics. Over 25% of the patients who gave consent were ambivalent about the benefit of antibiotic therapy. Predictably there was no evidence of an association between expectations and time to cure in those that gave consent. CONCLUSIONS: Selection bias occurs if patients with strong expectations refuse to participate in a trial and if the success of the intervention depends in part on a patient's expectations. Methods that adjust for selection bias are recommended for trials where placebo effects are either of interest or could be an important component of an intervention.

Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice.

BACKGROUND: Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care. However, it is not clear whether antibiotics improve the outcome for patients with clinically diagnosed acute rhinosinusitis. We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinically diagnosed in a general practice setting. METHODS: We conducted a randomized, placebo-controlled, double-blind trial with 252 adults recruited at 24 general practices and 2 outpatient clinics. Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours. Patients were given amoxicillin, 875 mg, and clavulanic acid, 125 mg, or placebo twice daily for 6 days. Main outcome measures were time to cure (primary outcome), number of days during which rhinosinusitis restricted activities at home or work, and frequency of adverse effects (secondary outcomes). RESULTS: The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 (95% confidence interval [CI], 0.68-1.45) on time to cure and 1.28 (95% CI, 0.80-2.05) in the prespecified subgroup of patients with a positive rhinoscopy result. At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 (95% CI, -0.93 to 0.34) in the number of days with restrictions due to rhinosinusitis and -0.60 (95% CI, -1.41 to 0.21) in patients with a positive rhinoscopy result. At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea (odds ratio, 3.89; 95% CI, 2.09-7.25). CONCLUSIONS: Adult patients in general practice with clinically diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects.

The clinical diagnosis of acute bacterial rhinosinusitis in general practice and its therapeutic consequences.

In a randomized double-blind trial 251 adults with sinusitis-like symptoms were given amoxicillin/clavulanate or placebo for 6 days. Seven diagnostic indicators for acute bacterial rhinosinusitis are compared by their accuracy assuming a latent class model and by the treatment effect that they would have had if used to select a subset of patients for antibiotic treatment. Under a latent class model, radiography is a more efficient indicator then C reactive protein (CRP), which is, in turn, more efficient than other clinical signs and symptoms. However, a history of purulent nasal discharge, and signs of pus in the nasal cavity and throat, are better criteria than radiography or CRP for selecting those patients who will benefit from antibiotic treatment. These contradictory results are a salutary reminder that diagnostic indicators need to be evaluated in terms of therapeutic consequences for the patient.