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Updated: Oct 26, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a
Simon de Lusignan1, Mark Joy2, Julian Sherlock3
1Professor of Primary Care & Clinical Informatics, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK simon.delusignan@phc.ox.ac.uk.
Background:
The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the early primary care management of coronavirus 2019 disease (COVID-19).
Aim:
To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice.
Design & Setting:
Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).
Method:
Negative binomial models were used to compare azithromycin and doxycycline prescribing, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years, and 95% confidence intervals (95% CI).
Results:
Azithromycin prescriptions increased 7% in 2020 compared with 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4%, respectively) while ILI rose slightly (6.4%). The overall percentage of RTI-prescribed azithromycin rose from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214%; 95% CI = 0.211 to 0.217); doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93%; 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22; 95% CI = 1.19 to 1.26; P<0.0001). For every unit rise in confirmed COVID-19 there was an associated 3% rise in prescription (IRR = 1.03; 95% CI = 1.02 to 1.03; P<0.0001); whereas these measures were static for doxycycline.
Conclusion:
PRINCIPLE demonstrates scope for improved antimicrobial stewardship during a pandemic.
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