The Safety of Delayed Versus Immediate Antibiotic Prescribing for Upper Respiratory Tract Infections

Abstract

Background: This study aimed to evaluate the clinical safety of delayed antibiotic prescribing for upper respiratory tract infections (URTIs), which is recommended in treatment guidelines for less severe cases.

Methods: Two population-based cohort studies used the English Clinical Practice Research Databank and Welsh Secure Anonymized Information Linkage, containing electronic health records from primary care linked to hospital admission records. Patients with URTI and prescriptions of amoxicillin, clarithromycin, doxycycline, erythromycin, or phenoxymethylpenicillin were identified. Patients were stratified according to delayed and immediate prescribing relative to URTI diagnosis. Outcome of interest was infection-related hospital admission after 30 days.

Results: The population included 1.82 million patients with an URTI and antibiotic prescription; 91.7% had an antibiotic at URTI diagnosis date (immediate) and 8.3% had URTI diagnosis in 1-30 days before (delayed). Delayed antibiotic prescribing was associated with a 52% increased risk of infection-related hospital admissions (adjusted hazard ratio, 1.52; 95% confidence interval, 1.43-1.62). The probability of delayed antibiotic prescribing was unrelated to predicted risks of hospital admission. Analyses of the number needed to harm showed considerable variability across different patient groups (median with delayed antibiotic prescribing, 1357; 2.5% percentile, 295; 97.5% percentile, 3366).

Conclusions: This is the first large population-based study examining the safety of delayed antibiotic prescribing. Waiting to treat URTI was associated with increased risk of hospital admission, although delayed antibiotic prescribing was used similarly between high- and low-risk patients. There is a need to better target delayed antibiotic prescribing to URTI patients with lower risks of complications.

Keywords: antibiotics; effectiveness; epidemiology; primary care; upper respiratory tract infections.

Figure 1.

Diagrammatic representation of the main inclusion criteria in this study. Abbreviation: URTI, upper respiratory tract infection.

Figure 2.

HRs of infection-related hospital admission in patients with delayed compared with immediate antibiotic prescribing overall and stratified by age, sex, Charlson comorbidity, type of infection, and calendar time period. x axis: fully adjusted HR over follow-up (95% CI). Models included delayed prescribing, calendar year, and month of the date of antibiotic prescription, Charlson comorbidity index, BMI categories, smoking history, IMD quintiles, flu vaccination, outpatient referral, and hospitalization in the previous year. Abbreviations: BMI, body mass index; CI, confidence interval; CPRD, Clinical Practice Research Datalink; HR, hazard ratio; IMD, Index of Multiple Deprivation; IRR, incidence rate ratio; SAIL, Secure Anonymized Information Linkage.

Figure 3.

IRRs of infection-related hospital admissions at each day of follow-up in patients with delayed or immediate antibiotic prescribing (age- and sex-matched cohorts). x axis: days after an antibiotic prescription; y axis: age- and sex-adjusted IRR. *Immediate antibiotic prescribing; □, delayed antibiotic prescribing; reference is days 24–30 after antibiotic prescribing in patients with immediate antibiotic prescribing. Abbreviation: IRR, incidence rate ratio. Panel A = CPRD (Clinical Practice Research Datalink); panel B = SAIL (Secure Anonymized Information Linkage).

Figure 4.

Percentage of patients with URTI who received a delayed antibiotic prescription in patient subgroups with different predicted risks of infection-related hospital admission (stratified by calendar time). y axis: percentage of delayed antibiotic prescribing; x axis: deciles of predicted risk of infection-related hospital admission (%) (in CPRD based on the risk prediction model developed in patients with immediate antibiotic prescribing; details on the prediction model are found in the Supplementary Material). *black, 2000–2004; □ red, 2005–2009; ∆ blue, 2010+. Abbreviations: CPRD, Clinical Practice Research Datalink; URTI, upper respiratory tract infection.