For patients with pharyngotonsillitis as a result of infection with group A streptococci, treatment with penicillin V four times a day for 5 days was comparable with penicillin V three times a day for 10 days, according to a study published in BJM.

Researchers conducted a randomized, phase 4, parallel study with noninferiority design to assess if the total exposure to penicillin V might be reduced while maintaining clinical efficacy against streptococcal infection (Clinical Trial identifier NCT02712307). Patients who were diagnosed with group A streptococcus infection and met 3 or 4 of the Centor criteria, were randomly assigned to receive penicillin V 800 mg 4 times daily for 5 days, or penicillin V 1000 mg 3 times daily for 10 days. Patients or guardians completed patient diaries throughout the course of treatment and a test of cure was completed at the end of the antibiotic regimen. The primary noninferiority outcome was defined as a clinical cure at the test of cure, and secondary outcomes were bacterial eradication, frequency of relapses or complications, and adverse events.

Of the 433 patients included in this study, 212 completed the 5-day intervention protocol and 210 completed the 10-day intervention protocol. The 5-day intervention cohort comprised 65.1% women and girls, 19.3% patients aged ≤12 years, and 74.1% aged ≥18 years; the 10-day intervention cohort similarly composed. The 5-day intervention cohort had an 89.6% test of cure rate, and the 10-day intervention cohort had a 93.3% test of cure rate, thus demonstrating that the 5-day treatment course was noninferior to the 10-day regimen. Subgroup analysis did not indicate any treatment differences between gender or age.

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In regards to secondary outcomes, 80.4% of the 5-day cohort and 90.7% of the 10-day cohort had bacterial eradication. Conversely, 4.5% of the 5-day cohort and 3.9% of the 10-day cohort had a relapse within 1 month; further, no patients in the 5-day cohort and 2.1% of the 10-day cohort had complications. There were no serious adverse events reported, but the 10-day cohort had increased reports of mild or moderate adverse events reported when compared with the 5-day cohort.

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Limitations of this study included the lack of double-blinding and of nonrecruitment logs, as well as not including bacteriologic outcomes at a follow-up.

The researchers concluded “[5] days of treatment with penicillin V [4] times daily was non-inferior in clinical outcome for patients with pharyngotonsillitis caused by group A streptococci and might be an alternative to the currently recommended 10 day regimen.”


Skoog Ståhlgren G, Tyrstrup M, Edlund C, et al. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. BMJ. 2019;367:l5337.