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

Abstract

Objective To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. Design Open label, randomised controlled non-inferiority study. Setting 17 primary healthcare centres in Sweden between September 2015 and February 2018. Participants Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). Interventions Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). Main outcome measures Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. Results Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval −9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. Conclusions Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. Trial registration EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307 .

Paediatrics: how to manage pharyngitis in an era of increasing antimicrobial resistance

“…A recent study reported that carriage cleared in 156 of 194 children and adults aged 6 years or older randomized to penicillin 800 mg qid for 5 days (80%) versus in 165 of 182 randomized to 1000 mg tid for 10 days (91%; difference −10.2%, 95% CI −17.8 to −2.7%). 74 Symptoms resolved earlier with the higher daily dose but rates of clinical cure at 5–7 days, relapse and complications were equivalent with the two regimens. To sum up, the optimal duration of treatment with oral penicillin to prevent RF is not known but 10 days is slightly more likely than 5 days to clear carriage.…”

A Case of Co-occurrence of COVID-19 and Group A Streptococcal Pharyngitis

“…GAS pharyngitis is a treatable condition. The antibiotic of choice is mainly penicillin, and in patients with penicillin allergy, cephalosporin or macrolides can be used [10][11][12]. The treatment of GAS is paramount to avoid complications.…”

Duration of antibiotic therapy for common infections

“…(30) Another study also showed equivalent clinical cure but slightly less (80% vs 90%) bacterial eradication in the 5 day group compared to 10 days of penicillin. (31) Guidelines from the United Kingdom recommend a 5-10-day course of penicillin (10 days if recurrent infection) whereas the Canadian Pediatric Society recommends 10 days of oral penicillin or amoxicillin. (Top, Sauve et al, In Press) (32)…”