Jason E Lang1,2, Christoph P Hornik1,2, Carrie Elliott2, Adam Silverstein2, Chi Hornik1,2, Amira Al-Uzri3, Miroslava Bosheva4, John S Bradley5, Charissa Fay Corazon Borja-Tabora6, David Di John7, Ana Mendez Echevarria8, Jessica E Ericson9, David Friedel10, Ferenc Gonczi11, Marie Grace Dawn Isidro12, Laura P James13, Krisztina Kalocsai14, Ioannis Koutroulis15, Istvan Laki16, Anna Lisa T Ong-Lim17, Marta Nad18, Gabor Simon19, Salma Syed20, Eva Szabo21, Daniel K Benjamin1,2, Michael Cohen-Wolkowiez1,2. 1. From the Department of Pediatrics. 2. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. 3. Oregon Health and Science University, Portland, Oregon. 4. Medical University, Plovdiv, Bulgaria. 5. Rady Children's Hospital, the University of California San Diego, San Diego, California. 6. Research Institute for Tropical Medicine, Manila, Philippines. 7. Kirk Kerkorian School of Medicine at UNLV, Las Vegas, Nevada. 8. Pediatric Infectious and Tropical Diseases Department, Hospital Universitario La Paz, Madrid, Spain. 9. Penn State College of Medicine, Hershey, Pennsylvania. 10. Virginia Commonwealth University Medical Center, Richmond, Virginia. 11. University of Debrecen Clinical Center Infectology Clinic, Debrecen, Hungary. 12. West Visayas State University Medical Center, Iloilo City, Philippines. 13. Arkansas Children's Hospital Research Institute, Little Rock, Arkansas. 14. Dél-pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary. 15. Children's National Hospital, Washington, DC. 16. Pulmonary Hospital, Törökbálint, Hungary. 17. Philippine General Hospital, University of the Philippines Manila, Philippines. 18. Kanizsai Dorottya Hospital, Nagykanizsa, Hungary. 19. Fejér County Szent György University Teaching Hospital, Székesfehérvár, Hungary. 20. East Carolina University, Brody School of Medicine, Greenville, North Carolina. 21. Csolnoky Ferenc Hospital, Veszprém, Hungary.
Abstract
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.
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.
Authors: Thomas M File; Barbara Rewerska; Violeta Vucinic-Mihailovic; Joven Roque V Gonong; Anita F Das; Kara Keedy; David Taylor; Amanda Sheets; Prabhavathi Fernandes; David Oldach; Brian D Jamieson Journal: Clin Infect Dis Date: 2016-07-22 Impact factor: 9.079
Authors: T Heiskanen-Kosma; M Korppi; C Jokinen; S Kurki; L Heiskanen; H Juvonen; S Kallinen; M Stén; A Tarkiainen; P R Rönnberg; M Kleemola; P H Mäkelä; M Leinonen Journal: Pediatr Infect Dis J Date: 1998-11 Impact factor: 2.129
Authors: Christopher R Cannavino; Agnes Nemeth; Bartosz Korczowski; John S Bradley; Tanya O'Neal; Alena Jandourek; H David Friedland; Sheldon L Kaplan Journal: Pediatr Infect Dis J Date: 2016-07 Impact factor: 2.129
Authors: Daniel Gonzalez; Laura P James; Amira Al-Uzri; Miroslava Bosheva; Felice C Adler-Shohet; Susan R Mendley; John S Bradley; Claudia Espinosa; Eva Tsonkova; Kathryn Moffett; Lucila Marquez; Kari A Simonsen; Stefan Stoilov; Felix Boakye-Agyeman; Theresa Jasion; Christoph P Hornik; Robert Hernandez; Daniel K Benjamin; Michael Cohen-Wolkowiez Journal: Antimicrob Agents Chemother Date: 2018-07-27 Impact factor: 5.191