The UK-wide PRINCIPLE (Platform Randomized trial of Interventions against COVID-19 In older PeopLE) trial has demonstrated that the commonly used antibiotics azithromycin and doxycycline are not generally effective treatments for coronavirus.

This overturns previous clinical guidance in England which suggested both drugs might be prescribed to COVID-19 patients. Doxycycline in particular is prescribed orally for suspected pneumonia if the cause is bacterial or unclear. Current clinical guidance in England also recommends it for pneumonia caused by COVID-19; however, the PRINCIPLE trial has shown that doxycycline should not be used in this way.

The key clinical findings are as follows:

Azithromycin:
– 526 participants were given 500 mg of azithromycin daily for 3 days
– This group was compared with a control group of 862 participants
– Both groups were observed over the first 14 days of COVID-19 infection
– The study failed to find a meaningful difference in outcomes between azithromycin and conventional treatments
– Azithromycin did not reduce hospitalisations or deaths

Doxycycline:
– 798 partcipants were given 200 mg doxycycline on the first day and then 100mg for the next 6 days
– This group was then compared with a control group of 994 participants
– Both groups were observed over 14 days of COVID-19 infection
– Doxycycline has a very small clinical benefit (1 day reduced recovery, 2% less hospitalisation)

Professor Chris Butler from the University of Oxford’s Nuffield Department of Primary Care Health Sciences and Co-Lead of the PRINCIPLE trial, said:”Azithromycin and doxycycline have anti-inflammatory, antibacterial and possibly antiviral effects, and so were considered as potential treatments for COVID-19 in the community.

“While we are completing the analysis of the full range of study outcomes, and in different patient groups, our findings show that a three-day course of azithromycin or a seven-day course of doxycycline has no important clinical benefit in terms of the time taken to feeling recovered, and so will not help most patients with COVID-19 in the early stages their illness.

“These are two important findings, as both azithromycin and doxycycline have been used for treating COVID-19 in the community even in the absence of suspected bacterial pneumonia, so this practice should now be re-considered – particularly because overuse of antibiotics in the community can fuel the emergence of antimicrobial resistance.”