METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario).
RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences.
CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.
METHODS: This was an open-label, prospective, multicentre, randomized trial. Three hospitals where the current protocol was to administer prophylactic amoxycillin-clavulanic acid served as the sites of recruitment. Women who delivered vaginally beyond 24+ 0 weeks of gestation with ragged membranes were invited to participate in the trial and randomized into prophylaxis or expectant management with medical advice by blocks of 10, at a 1:1 ratio. A medication adherence diary was provided and patients followed up at 2 weeks and 6 weeks postpartum.
RESULTS: A total of 6569 women gave birth vaginally in three centres during the trial period, of which 10.9% had ragged membranes. The incidence of endometritis was not significantly raised in women with or without prophylaxis (0.90% vs 0.29%; p = 0.60). All cases of endometritis presented within the first 2 weeks and preventive use of antibiotics did not ameliorate the severity of endometritis since rates of ICU admission, surgical evacuation and transfusion were comparable.
CONCLUSION: Preventive use of antibiotics after vaginal delivery in women with ragged placental membranes did not result in a reduction of endometritis. Educating women on the signs and symptoms of endometritis would suffice. Based on the reported incidence of ragged membranes, a change in practice would result in 1500 less prescriptions of antibiotics per annum in these three centres.
TRIAL REGISTRATION: NCT03459599 (Retrospectively registered on 9 March 2018).