دورية أكاديمية

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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Keij FM; Department of Paediatrics, Division of Neonatology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, Netherlands; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands. Electronic address: f.keij@erasmusmc.nl., Kornelisse RF; Department of Paediatrics, Division of Neonatology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, Netherlands., Hartwig NG; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands., van der Sluijs-Bens J; Department of Paediatrics, Division of Neonatology, Maxima Medical Centre, Veldhoven, Netherlands., van Beek RHT; Department of Paediatrics, Amphia Hospital, Breda, Netherlands., van Driel A; Department of Paediatrics, IJsselland Hospital, Capelle aan den IJssel, Netherlands., van Rooij LGM; Department of Paediatrics, Medisch Spectrum Twente, Enschede, Netherlands., van Dalen-Vink I; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands., Driessen GJA; Department of Paediatrics, Juliana Children's Hospital, Haga Teaching Hospital, the Hague, Netherlands., Kenter S; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands., von Lindern JS; Department of Paediatrics, Groene Hart Hospital, Gouda, Netherlands., Eijkemans M; Department of Paediatrics, Catharina Hospital, Eindhoven, Netherlands., Stam-Stigter GM; Department of Paediatrics, St Antonius Hospital, Nieuwegein, Netherlands., Qi H; Department of Biostatistics, Erasmus University Medical Centre, Rotterdam, Netherlands., van den Berg MM; Department of Paediatrics, Haaglanden Medical Centre, the Hague, Netherlands., Baartmans MGA; Department of Paediatrics, Maasstad Hospital, Rotterdam, Netherlands., van der Meer-Kappelle LH; Department of Paediatrics, Reinier de Graaf Hospital, Delft, Netherlands., Meijssen CB; Department of Paediatrics, Meander Medical Centre, Amersfoort, Netherlands., Norbruis OF; Department of Paediatrics, Isala Hospital, Zwolle, Netherlands., Heidema J; Department of Paediatrics, St Antonius Hospital, Nieuwegein, Netherlands., van Rossem MC; Department of Paediatrics, Rijnstate Hospital, Arnhem, Netherlands., den Butter PCP; Department of Paediatrics, Ikazia Hospital, Rotterdam, Netherlands., Allegaert K; Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, Netherlands; Department of Development and Regeneration and Department of Pharmaceutical and Pharmacological Sciences, Catholic University of Leuven, Leuven, Belgium., Reiss IKM; Department of Paediatrics, Division of Neonatology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, Netherlands., Tramper-Stranders GA; Department of Paediatrics, Division of Neonatology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, Netherlands; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands. Electronic address: g.tramper@franciscus.nl.
المصدر: The Lancet. Child & adolescent health [Lancet Child Adolesc Health] 2022 Nov; Vol. 6 (11), pp. 799-809. Date of Electronic Publication: 2022 Sep 09.
نوع المنشور: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101712925 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-4650 (Electronic) Linking ISSN: 23524642 NLM ISO Abbreviation: Lancet Child Adolesc Health Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, UK] : Elsevier Ltd., [2017]-
مواضيع طبية MeSH: Amoxicillin-Potassium Clavulanate Combination*/adverse effects , Bacterial Infections*/drug therapy, Adolescent ; Adult ; Amoxicillin/adverse effects ; Anti-Bacterial Agents/adverse effects ; Child ; Child, Preschool ; Clavulanic Acid/adverse effects ; Humans ; Infant ; Infant, Newborn ; Reinfection ; Research ; Treatment Outcome ; Young Adult
مستخلص: 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 [<1%] of 252 neonates in the amoxicillin-clavulanic acid group vs one [<1%] of 252 neonates in the intravenous antibiotics group; between-group difference 0 [95% CI -1·9 to 1·9]; p non-inferiority <0·0001). No statistically significant differences were observed in reported adverse events (127 [50%] vs 113 [45%]; p=0·247). In the intention-to-treat population, median duration of hospitalisation was significantly shorter in the amoxicillin-clavulanic acid group than the intravenous antibiotics group (3·4 days [95% CI 3·0-4·1] vs 6·8 days [6·5-7·0]; p<0·0001).
Interpretation: An early intravenous-to-oral antibiotic switch with amoxicillin-clavulanic acid is non-inferior to a full course of intravenous antibiotics in neonates with probable bacterial infection and is not associated with an increased incidence of adverse events.
Funding: The Netherlands Organization for Health Research and Development, Innovatiefonds Zorgverzekeraars, and the Sophia Foundation for Scientific Research.
Competing Interests: Declaration of interests We declare no competing interests.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
التعليقات: Comment in: Acta Paediatr. 2023 Apr;112(4):883-884. (PMID: 36578094)
سلسلة جزيئية: ClinicalTrials.gov NCT03247920
EudraCT 2016-004447-36
المشرفين على المادة: 0 (Anti-Bacterial Agents)
23521W1S24 (Clavulanic Acid)
74469-00-4 (Amoxicillin-Potassium Clavulanate Combination)
804826J2HU (Amoxicillin)
تواريخ الأحداث: Date Created: 20220911 Date Completed: 20221018 Latest Revision: 20230314
رمز التحديث: 20231215
DOI: 10.1016/S2352-4642(22)00245-0
PMID: 36088952
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-4650
DOI:10.1016/S2352-4642(22)00245-0