Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines.

OBJECTIVE
To evaluate the duration of prescriptions for antibiotic treatment for common infections in English primary care and to compare this with guideline recommendations.


DESIGN
Cross sectional study.


SETTING
General practices contributing to The Health Improvement Network database, 2013-15.


PARTICIPANTS
931 015 consultations that resulted in an antibiotic prescription for one of several indications: acute sinusitis, acute sore throat, acute cough and bronchitis, pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD), acute otitis media, acute cystitis, acute prostatitis, pyelonephritis, cellulitis, impetigo, scarlet fever, and gastroenteritis.


MAIN OUTCOME MEASURES
The main outcomes were the percentage of antibiotic prescriptions with a duration exceeding the guideline recommendation and the total number of days beyond the recommended duration for each indication.


RESULTS
The most common reasons for antibiotics being prescribed were acute cough and bronchitis (386 972, 41.6% of the included consultations), acute sore throat (239 231, 25.7%), acute otitis media (83 054, 8.9%), and acute sinusitis (76 683, 8.2%). Antibiotic treatments for upper respiratory tract indications and acute cough and bronchitis accounted for more than two thirds of the total prescriptions considered, and 80% or more of these treatment courses exceeded guideline recommendations. Notable exceptions were acute sinusitis, where only 9.6% (95% confidence interval 9.4% to 9.9%) of prescriptions exceeded seven days and acute sore throat where only 2.1% (2.0% to 2.1%) exceeded 10 days (recent guidance recommends five days). More than half of the antibiotic prescriptions were for longer than guidelines recommend for acute cystitis among females (54.6%, 54.1% to 55.0%). The percentage of antibiotic prescriptions exceeding the recommended duration was lower for most non-respiratory infections. For the 931 015 included consultations resulting in antibiotic prescriptions, about 1.3 million days were beyond the durations recommended by guidelines.


CONCLUSION
For most common infections treated in primary care, a substantial proportion of antibiotic prescriptions have durations exceeding those recommended in guidelines. Substantial reductions in antibiotic exposure can be accomplished by aligning antibiotic prescription durations with guidelines.


Multiple imputation
Although the quantity of antibiotics prescribed was available for virtually all prescriptions (>99%) the daily dose and hence duration was missing between 10-20% of the prescriptions, dependent on the condition. Multiple imputation via chained equations using sequential regression trees were used to impute these missing durations. 38 This non-parametric method can capture potential complex interactions and non-linear relationships in the underlying data and can result in more plausible imputations in complex settings than standard sequential regression imputation techniques. 38 For all indications durations were imputed based on practice identifier, age, antibiotic group (different groups for each condition based on the first 5 characters of the Anatomical Therapeutic Chemical (ATC) code and the number of observations, except for azithromycin, which was used as a separate group given its long half-life) and the quantity of antibiotics being prescribed. Regarding the group of antibiotics, separate categories were used as long as there were at least 100 observations with that antibiotic group. The remaining antibiotics were grouped in the 'other antibiotic' category.
In addition, we evaluated whether one or more of the following potential predictors of antibiotic duration should be included in the imputation models as well using models restricted to complete cases: sex, chronic kidney disease, chronic respiratory disease, asthma, coronary heart disease, immunosuppressive disease, use of immunosuppressive drugs, use of systemic corticosteroids, or use of inhaled corticosteroids. We included these additional variables in imputation models if they had p<0.01 in the multivariable model. In total, 10 datasets were imputed for each condition.
Although there was some variation in the imputed value for individual prescriptions, the summary estimates for each imputed dataset were virtually identical and therefore 10 imputations was judged sufficient.
The resulting imputations were almost solely driven by the combination of the antibiotic groups, age and the total quantity prescribed, e.g. the number of tablets. Occasionally some other variables, such as chronic kidney disease were associated with the treatment duration, however this had a negligible influence on the summary estimates for each imputed dataset.

Supplementary file 3: Additional figures and results of additional analyses.
Fig S1 Durations of antibiotic prescriptions for acute sore throat. The purple portions of the bars are observed data for penicillin V, the blue portions are imputed data for penicillin V, the green portions are observed data for other antibiotics, and the red portions are imputed data for other antibiotics. The dark blue dotted vertical lines represent the main analysis using durations recommended by 2013 PHE guidance. That guidance recommends 10 days for penicillin V and 5 days for clarithromycin.

Table S4
The percentage of antibiotics with a duration exceeding the guideline recommendations when restricting the analysis to data without missing values.