Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

Autor:	Lang JE; From the Department of Pediatrics.; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Hornik CP; From the Department of Pediatrics.; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Elliott C; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Silverstein A; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Hornik C; From the Department of Pediatrics.; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Al-Uzri A; Oregon Health and Science University, Portland, Oregon., Bosheva M; Medical University, Plovdiv, Bulgaria., Bradley JS; Rady Children's Hospital, the University of California San Diego, San Diego, California., Borja-Tabora CFC; Research Institute for Tropical Medicine, Manila, Philippines., Di John D; Kirk Kerkorian School of Medicine at UNLV, Las Vegas, Nevada., Mendez Echevarria A; Pediatric Infectious and Tropical Diseases Department, Hospital Universitario La Paz, Madrid, Spain., Ericson JE; Penn State College of Medicine, Hershey, Pennsylvania., Friedel D; Virginia Commonwealth University Medical Center, Richmond, Virginia., Gonczi F; University of Debrecen Clinical Center Infectology Clinic, Debrecen, Hungary., Isidro MGD; West Visayas State University Medical Center, Iloilo City, Philippines., James LP; Arkansas Children's Hospital Research Institute, Little Rock, Arkansas., Kalocsai K; Dél-pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary., Koutroulis I; Children's National Hospital, Washington, DC., Laki I; Pulmonary Hospital, Törökbálint, Hungary., Ong-Lim ALT; Philippine General Hospital, University of the Philippines Manila, Philippines., Nad M; Kanizsai Dorottya Hospital, Nagykanizsa, Hungary., Simon G; Fejér County Szent György University Teaching Hospital, Székesfehérvár, Hungary., Syed S; East Carolina University, Brody School of Medicine, Greenville, North Carolina., Szabo E; Csolnoky Ferenc Hospital, Veszprém, Hungary., Benjamin DK Jr; From the Department of Pediatrics.; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina., Cohen-Wolkowiez M; From the Department of Pediatrics.; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Jazyk:	angličtina
Zdroj:	The Pediatric infectious disease journal [Pediatr Infect Dis J] 2022 Jul 01; Vol. 41 (7), pp. 556-562. Date of Electronic Publication: 2022 Jun 07.
DOI:	10.1097/INF.0000000000003559
Abstrakt:	Background: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. Methods: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. Results: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. Conclusions: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP. Competing Interests: J.E.L. receives salary support for research from the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org), the American Lung Association, National Heart Lung and Blood Institute (NHLBI) (HL145415), University of Arkansas for Medical Sciences and Regeneron Pharmaceuticals; C.P.H. receives salary support for research from National Institute for Child Health and Human Development (NICHD) (1K23HD090239), the National Heart Lung and Blood Institute (NHLBI) (R61/R33HL147833), the US Food and Drug Administration (1R01-FD006099, PI Laughon; and 5U18-FD006298, PI: Benjamin), the U.S. government for his work in pediatric clinical pharmacology (Government Contract HHSN275201800003I, PI: Benjamin under the Best Pharmaceuticals for Children Act), the nonprofit Burrhoughs Wellcome Fund, and other sponsors for drug development in adults and children (https://dcri.org/about-us/conflict-of-interest/). M.C.-W. receives support for research from the National Institutes of Health (1R01-HD076676-01A1 and 1K24-AI143971), National Institute of Allergy and Infectious Diseases (HHSN272201500006I and HHSN272201300017I), NICHD (HHSN275201000003I), Federal Drug Administration (5U18-FD006298), and industry for drug development in adults and children. The other authors have no conflicts of interest to disclose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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