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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1097/inf.0000000000003559

Publication Info

Lang, Jason E, Christoph P Hornik, Carrie Elliott, Adam Silverstein, Chi Hornik, Amira Al-Uzri, Miroslava Bosheva, John S Bradley, et al. (2022). Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia. The Pediatric infectious disease journal, 41(7). pp. 556–562. 10.1097/inf.0000000000003559 Retrieved from https://hdl.handle.net/10161/31129.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Lang

Jason Lang

Associate Professor of Pediatrics

Jason E. Lang

Hornik

Christoph Paul Vincent Hornik

Samuel L. Katz Distinguished Professor of Pediatrics
Hornik

Chi Hornik

Associate Professor of Pediatrics

Chi Hornik is the Director of Heart Center Research and the Director of Critical Care Medicine Research in the Department of Pediatrics.  She is an Associate Professor in the Duke School of Medicine and the Duke Clinical Research Institute (DCRI).  She serves as Principal Investigator (PI) of Duke as a site for numerous studies and as clinical coordinating center PI of multi-center trials through the DCRI.   As a clinical specialist in neonatal and pediatric critical care, she is committed to ensuring that the research conducted has representation of children from all races/ethnic backgrounds and socio-economic status, in order to continue to move the needle forward to improve health for all children.

Benjamin

Daniel Kelly Benjamin

Kiser-Arena Distinguished Professor

Dr. Danny Benjamin is the Principal Investigator and Chair of the National Institute of Child Health and Human Development’s Pediatric Trials Network. The Network is responsible for designing and leading clinical trials of off-patent medicines in children of all ages across all therapeutic areas. The team has established, or is actively studying, the correct dosing and safety of more than 70 of the most commonly used medicines in children. Each of these trials is conducted under an Investigational New Drug (IND) application with guidance from the Food and Drug Administration for labeling.

The Pediatric Trials Network has directly impacted the healthcare of over 90% of American children.

Signature programs of the Network include clinical trials in premature, term infants, breast feeding mothers, and obese children. Over the past 10 years, Danny’s group has enrolled more premature infants, at more sites, in more clinical trials of off-patent anti-infectives under an IND than all other academic medical centers, pharmaceutical companies, and government agencies in the world, combined.

Danny is recognized by the National Institutes of Health as a premiere mentor and educator. His research program serves as a platform to train students and early career investigators. Danny’s group has a clinical research summer program for high school and college students that has a focus on trainees under-represented in medicine, and he is the primary mentor for medical students, residents, subspecialty fellows, and multiple junior faculty. He has been the primary or secondary mentor for 10 faculty who have received career development awards and who have then gone on to secure their own funding.

Danny's service to the community is expressed through his passion for coaching baseball. He has coached over 500 recreation league, travel league, and scholastic baseball games and he is the head coach of Smith Middle School, the 5-year reigning southern conference champions. Danny and his wife own a charitable non-profit that provides athletic and fitness opportunities for disadvantaged school-aged boys and girls.

Cohen-Wolkowiez

Michael Cohen-Wolkowiez

Kiser-Arena Distinguished Professor

Pediatric and adult clinical pharmacology and clinical trials.


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