Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin–clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial
| Autor: | Fleur M Keij, René F Kornelisse, Nico G Hartwig, Jacqueline van der Sluijs-Bens, Ron H T van Beek, Arianne van Driel, Linda G M van Rooij, Ilka van Dalen-Vink, Gertjan J A Driessen, Sandra Kenter, Jeannette S von Lindern, Marianne Eijkemans, Gerda M Stam-Stigter, Hongchao Qi, Maartje M van den Berg, Martin G A Baartmans, Laura H van der Meer-Kappelle, Clemens B Meijssen, Obbe F Norbruis, Jojanneke Heidema, Maaike C van Rossem, Paul C P den Butter, Karel Allegaert, Irwin K M Reiss, Gerdien A Tramper-Stranders |
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| Přispěvatelé: | Pediatrics, Epidemiology, Pharmacy |
| Rok vydání: | 2022 |
| Předmět: |
Adult
Adolescent Research Infant Newborn Amoxicillin Infant Bacterial Infections Amoxicillin-Potassium Clavulanate Combination Anti-Bacterial Agents Young Adult Treatment Outcome Child Preschool Reinfection Pediatrics Perinatology and Child Health Developmental and Educational Psychology Humans Child Clavulanic Acid |
| Zdroj: | The Lancet Child and Adolescent Health, 6(11), 799-809. Elsevier |
| ISSN: | 2352-4642 |
| Popis: | Background: Switching from intravenous antibiotic therapy to oral antibiotic therapy among neonates is not yet practised in high-income settings due to uncertainties about exposure and safety. We aimed to assess the efficacy and safety of early intravenous-to-oral antibiotic switch therapy compared with a full course of intravenous antibiotics among neonates with probable bacterial infection. Methods: In this multicentre, randomised, open-label, non-inferiority trial, patients were recruited at 17 hospitals in the Netherlands. Neonates (postmenstrual age ≥35 weeks, postnatal age 0–28 days, bodyweight ≥2 kg) in whom prolonged antibiotic treatment was indicated because of a probable bacterial infection, were randomly assigned (1:1) to switch to an oral suspension of amoxicillin 75 mg/kg plus clavulanic acid 18·75 mg/kg (in a 4:1 dosing ratio, given daily in three doses) or continue on intravenous antibiotics (according to the local protocol). Both groups were treated for 7 days. The primary outcome was cumulative bacterial reinfection rate 28 days after treatment completion. A margin of 3% was deemed to indicate non-inferiority, thus if the reinfection rate in the oral amoxicillin–clavulanic acid group was less than 3% higher than that in the intravenous antibiotic group the null hypothesis would be rejected. The primary outcome was assessed in the intention-to-treat population (ie, all patients who were randomly assigned and completed the final follow-up visit on day 35) and the per protocol population. Safety was analysed in all patients who received at least one administration of the allocated treatment and who completed at least one follow-up visit. Secondary outcomes included clinical deterioration and duration of hospitalisation. This trial was registered with ClinicalTrials.gov, NCT03247920, and EudraCT, 2016-004447-36. Findings: Between Feb 8, 2018 and May 12, 2021, 510 neonates were randomly assigned (n=255 oral amoxicillin–clavulanic group; n=255 intravenous antibiotic group). After excluding those who withdrew consent (n=4), did not fulfil inclusion criteria (n=1), and lost to follow-up (n=1), 252 neonates in each group were included in the intention-to-treat population. The cumulative reinfection rate at day 28 was similar between groups (one [non-inferiority |
| Databáze: | OpenAIRE |
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