PMID- 35675525
OWN - NLM
STAT- MEDLINE
DCOM- 20220610
LR  - 20240407
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Print)
IS  - 0891-3668 (Linking)
VI  - 41
IP  - 7
DP  - 2022 Jul 1
TI  - Solithromycin in Children and Adolescents With Community-acquired Bacterial 
      Pneumonia.
PG  - 556-562
LID - 10.1097/INF.0000000000003559 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Lang, Jason E
AU  - Lang JE
AUID- ORCID: 0000-0001-9115-5312
AD  - From the Department of Pediatrics.
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Hornik, Christoph P
AU  - Hornik CP
AUID- ORCID: 0000-0001-7056-8759
AD  - From the Department of Pediatrics.
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Elliott, Carrie
AU  - Elliott C
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Silverstein, Adam
AU  - Silverstein A
AUID- ORCID: 0000-0003-2013-5087
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Hornik, Chi
AU  - Hornik C
AUID- ORCID: 0000-0002-7656-3657
AD  - From the Department of Pediatrics.
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Al-Uzri, Amira
AU  - Al-Uzri A
AUID- ORCID: 0000-0001-6532-7117
AD  - Oregon Health and Science University, Portland, Oregon.
FAU - Bosheva, Miroslava
AU  - Bosheva M
AD  - Medical University, Plovdiv, Bulgaria.
FAU - Bradley, John S
AU  - Bradley JS
AD  - Rady Children's Hospital, the University of California San Diego, San Diego, 
      California.
FAU - Borja-Tabora, Charissa Fay Corazon
AU  - Borja-Tabora CFC
AUID- ORCID: 0000-0002-2056-7763
AD  - Research Institute for Tropical Medicine, Manila, Philippines.
FAU - Di John, David
AU  - Di John D
AUID- ORCID: 0000-0001-7191-0093
AD  - Kirk Kerkorian School of Medicine at UNLV, Las Vegas, Nevada.
FAU - Mendez Echevarria, Ana
AU  - Mendez Echevarria A
AD  - Pediatric Infectious and Tropical Diseases Department, Hospital Universitario La 
      Paz, Madrid, Spain.
FAU - Ericson, Jessica E
AU  - Ericson JE
AUID- ORCID: 0000-0002-8765-2065
AD  - Penn State College of Medicine, Hershey, Pennsylvania.
FAU - Friedel, David
AU  - Friedel D
AUID- ORCID: 0000-0001-6936-9082
AD  - Virginia Commonwealth University Medical Center, Richmond, Virginia.
FAU - Gonczi, Ferenc
AU  - Gonczi F
AD  - University of Debrecen Clinical Center Infectology Clinic, Debrecen, Hungary.
FAU - Isidro, Marie Grace Dawn
AU  - Isidro MGD
AD  - West Visayas State University Medical Center, Iloilo City, Philippines.
FAU - James, Laura P
AU  - James LP
AD  - Arkansas Children's Hospital Research Institute, Little Rock, Arkansas.
FAU - Kalocsai, Krisztina
AU  - Kalocsai K
AD  - Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet, Budapest, 
      Hungary.
FAU - Koutroulis, Ioannis
AU  - Koutroulis I
AUID- ORCID: 0000-0002-8396-9022
AD  - Children's National Hospital, Washington, DC.
FAU - Laki, Istvan
AU  - Laki I
AD  - Pulmonary Hospital, Torokbalint, Hungary.
FAU - Ong-Lim, Anna Lisa T
AU  - Ong-Lim ALT
AUID- ORCID: 0000-0002-3261-0167
AD  - Philippine General Hospital, University of the Philippines Manila, Philippines.
FAU - Nad, Marta
AU  - Nad M
AD  - Kanizsai Dorottya Hospital, Nagykanizsa, Hungary.
FAU - Simon, Gabor
AU  - Simon G
AD  - Fejer County Szent Gyorgy University Teaching Hospital, Szekesfehervar, Hungary.
FAU - Syed, Salma
AU  - Syed S
AUID- ORCID: 0000-0002-3307-8379
AD  - East Carolina University, Brody School of Medicine, Greenville, North Carolina.
FAU - Szabo, Eva
AU  - Szabo E
AUID- ORCID: 0000-0001-9301-9015
AD  - Csolnoky Ferenc Hospital, Veszprem, Hungary.
FAU - Benjamin, Daniel K Jr
AU  - Benjamin DK Jr
AUID- ORCID: 0000-0002-0764-8585
AD  - From the Department of Pediatrics.
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Cohen-Wolkowiez, Michael
AU  - Cohen-Wolkowiez M
AUID- ORCID: 0000-0002-2458-2266
AD  - From the Department of Pediatrics.
AD  - Duke Clinical Research Institute, Duke University Medical Center, Durham, North 
      Carolina.
CN  - SOLI-PEDS Program
LA  - eng
GR  - R61 HL147833/HL/NHLBI NIH HHS/United States
GR  - K23 HD083465/HD/NICHD NIH HHS/United States
GR  - K24 AI143971/AI/NIAID NIH HHS/United States
GR  - R21 HL145415/HL/NHLBI NIH HHS/United States
GR  - R01 FD006099/FD/FDA HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
GR  - R33 HL147833/HL/NHLBI NIH HHS/United States
GR  - K23 HD090239/HD/NICHD NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - HHSN275201000003C/AA/NIAAA NIH HHS/United States
GR  - R01 HD076676/HD/NICHD NIH HHS/United States
GR  - HHSN272201300017C/AI/NIAID NIH HHS/United States
GR  - HHSN272201300017I/AI/NIAID NIH HHS/United States
GR  - HHSN272201500006C/AI/NIAID NIH HHS/United States
GR  - U18 FD006298/FD/FDA HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20220607
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Macrolides)
RN  - 0 (Triazoles)
RN  - 9U1ETH79CK (solithromycin)
SB  - IM
MH  - Adolescent
MH  - Anti-Bacterial Agents/adverse effects
MH  - Child
MH  - *Community-Acquired Infections/drug therapy/microbiology
MH  - Humans
MH  - Macrolides/adverse effects
MH  - *Pneumonia, Bacterial/drug therapy/microbiology
MH  - Triazoles
PMC - PMC9199591
MID - NIHMS1795862
COIS- 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.
EDAT- 2022/06/09 06:00
MHDA- 2022/06/11 06:00
PMCR- 2023/07/01
CRDT- 2022/06/08 15:12
PHST- 2022/06/09 06:00 [pubmed]
PHST- 2022/06/11 06:00 [medline]
PHST- 2022/06/08 15:12 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - 00006454-202207000-00007 [pii]
AID - 10.1097/INF.0000000000003559 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2022 Jul 1;41(7):556-562. doi: 
      10.1097/INF.0000000000003559. Epub 2022 Jun 7.