Study Overview
Objective. To determine the efficacy and safety of delayed antibiotic prescribing strategies in acute uncomplicated respiratory infections.
Design. Randomized, multicenter, open-label clinical trial.
Setting and participants . The setting was 23 primary care centers in Spain. The study recruited patients who were 18 years of age or older with an acute uncomplicated respiratory infection (acute pharyngitis, rhinosinusitis, acute bronchitis, exacerbations of chronic bronchitis or mild to moderate chronic obstructive pulmonary disease). Patients with these infections were included by the physicians as long as they were unsure of whether to use antibiotics or not. The study protocol has been published elsewhere [1].
Intervention. Patients were randomized to 1 of 4 potential prescription strategies: (1) a delayed patient-led prescription strategy where patients were given an antibiotic prescription at first consultation but instructed to fill the prescription only if they felt substantially worse or saw no improvement in symptoms in the first few days after initial consultation; (2) a delayed prescription collection strategy requiring patients to collect their prescription from the primary care center reception desk 3 days after the first consultation; (3) an immediate prescription strategy; or (4) no antibiotic strategy. The patient-led and delayed collection strategies were considered delayed prescription strategies.
Main outcome measures . Duration of symptoms and severity of symptoms. Patients filled out a daily questionnaire for a maximum of 30 days, which listed common symptoms such as fever, discomfort or general pain, cough, difficulty sleeping, and changes in everyday life, and specific symptoms according to condition. Patients assessed severity of their symptoms using 6-point Likert scale, with scores of 1-2 considered mild, 3-4 moderate, and 5-6 severe. Secondary outcomes included antibiotic use, patient satisfaction, patients’ beliefs in the effectiveness of antibiotics, and absenteeism (absence from work or doing their daily activities).
Main results . A total of 405 patients were recruited, 398 of whom were included in the analysis. 136 patients (34.2%) were men. The mean (SD) age was 45 (17) years and 265 patients (72%) had at least a secondary education level. The most common infection was pharyngitis ( n = 184; 46.2%), followed by acute bronchitis ( n = 128; 32.2%). The mean severity of symptoms ranged from 1.8 to 3.5 points on the Likert scale, and mean (SD) duration of symptoms described on first visit was 6 (6) days. The mean (SD) general health status on first visit was 54 (20) based on a scale with 0 indicating worst health status and 100 indicating best health status. 314 patients (80.1%) were nonsmokers, and 372 patients (93.5%) did not have a respiratory comorbidity. The presence of symptoms on first visit was similar among the 4 groups.
The duration of the common symptoms of fever, discomfort or general pain, and cough was shorter in the immediate prescription group versus the no prescription group ( P < 0.05 for all). In the immediate prescription group, the duration of patient symptoms after first visit was significantly different from that of the prescription collection and patient-led prescription groups only for discomfort or general pain. The mean (SD) duration of severe symptoms was 3.6 (3.3) days for the immediate prescription group, 4.0 (4.2) days for the prescription collection group, 5.1 (6.3) days for the patient-led prescription group, and 4.7 (3.6) days for the no prescription group. The median (interquartile range [IQR]) of severe symptoms was 3 (1–4) days for the prescription collection group and 3 (2–6) days for the patient-led prescription group. The median (IQR) of the maximum severity for any symptom was 5 (3–5) for the immediate prescription group and the prescription collection group; 5 (4–5) for the patient-led prescription group; and 5 (4–6) for the no prescription group. Patients randomized to the no prescription strategy or to either of the delayed strategies used fewer antibiotics and less frequently believed in antibiotic effectiveness. Among patients in the immediate prescription group, 91.1% used antibiotics; in the delayed patient-led, delayed collection, and no prescription groups, the rates of antibiotic use were 32.6%, 23.0%, and 12.1%, respectively. There were very few adverse events across groups, although the no prescription group had 3 adverse events compared with 0-1 in the other groups. Satisfaction was similar across groups.
Conclusion. Delayed strategies were associated with slightly greater but clinically similar symptom burden and duration and also with substantially reduced antibiotic use when compared with an immediate strategy.
Commentary
Acute respiratory infections are a common reasons for physician visits. These infections tend to be self-limiting and overuse of antibiotics for these infections is widespread. Approximately 60% of patients with a sore throat and ~70% of patients with acute uncomplicated bronchitis receive antibiotic prescriptions despite the literature suggesting no or limited benefit [2,3].Antibiotic resistance is a growing problem and the main cause of this problem is misuse of antibiotics.
Often physicians feel pressured into prescribing anti-biotics due to patient expectation and patient satisfaction metrics. In the face of the critical need to reduce overuse, delayed antibiotic prescribing strategies offers a compromise between immediate and no prescription [4]. Delayed prescribing strategies have been evaluated previously [5–8], with findings suggesting they do reduce antibiotic use. This study strengthens the evidence base supporting the delayed strategy.
This study has a few limitations. The sample size was small, and symptom data was obtained via patient self-report. In addition, the randomization procedure was not described. However, the investigators were able to achieve good patient retention, with very few patients lost to follow-up. The investigators used an intention to treat analysis; thus, the estimate of treatment effect size can be considered conservative.
In terms of baseline characteristics of the study participants, there was a lower overall education level, fewer smokers, and less respiratory comorbidity (defined as only cardiovascular comorbidity [ P = 0.12] and diabetes [ P = 0.19]) in the patient-led group. Otherwise, groups were very well-matched. Most patients in the study had pharyngitis and bronchitis, limiting the inferences for patients with rhinosinusitis or exacerbation of mild-to-moderate COPD.
Applications for Clinical Practice
Delayed antibiotic prescribing for acute uncomplicated respiratory infections appears to be an acceptable strategy for reducing the overuse of antibiotics. As patients may lack knowledge of this prescribing strategy [9], clinicians may need to spend time explaining the concept. Using the term “back-up antibiotics” instead of “delayed prescription” [10] may help to increase patients’ understanding and acceptance.
—Ajay Dharod, MD