Dataset Information

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.

SUBMITTER: Lang JE

PROVIDER: S-EPMC9199591 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Lang Jason E JE Hornik Christoph P CP Elliott Carrie C Silverstein Adam A Hornik Chi C Al-Uzri Amira A Bosheva Miroslava M Bradley John S JS Borja-Tabora Charissa Fay Corazon CFC Di John David D Mendez Echevarria Ana A Ericson Jessica E JE Friedel David D Gonczi Ferenc F Isidro Marie Grace Dawn MGD James Laura P LP Kalocsai Krisztina K Koutroulis Ioannis I Laki Istvan I Ong-Lim Anna Lisa T ALT Nad Marta M Simon Gabor G Syed Salma S Szabo Eva E Benjamin Daniel K DK Cohen-Wolkowiez Michael M

The Pediatric infectious disease journal 20220607 7

<h4>Background</h4>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.<h4>Methods</h4>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 1 ...[more]

PMID: 35675525

Similar Datasets

Project description:BackgroundPneumonia is the leading cause of mortality in pediatric population. The etiology of pneumonia in this population is variable and changes according to age and disease severity and where the study is conducted. Our aim was to determine the etiology of community-acquired pneumonia (CAP) in children aged 1 month to 17 years admitted to 13 Colombian hospitals.MethodsProspective cohort study. Hospitalized children with radiologically confirmed CAP and ≤ 15 days of symptoms were included and followed together with a control group. Induced sputum (IS) was submitted for stains and cultures for pyogenic bacteria and Mycobacterium tuberculosis, and multiplex PCR (mPCR) for bacteria and viruses; urinary antigens for pneumococcus and Legionella pneumophila; nasopharyngeal swabs for viruses, and paired serology for atypical bacteria and viruses. Additional cultures were taken at the discretion of primary care pediatricians.ResultsAmong 525 children with CAP, 71.6% had non-severe pneumonia; 24.8% severe and 3.6% very severe pneumonia, and no fatal cases. At least one microorganism was identified in 84% of children and 61% were of mixed etiology; 72% had at least one respiratory virus, 28% pyogenic bacteria and 21% atypical bacteria. Respiratory syncytial virus, Parainfluenza, Rhinovirus, Influenza, Mycoplasma pneumoniae, Adenovirus and Streptococcus pneumoniae were the most common etiologies of CAP. Respiratory syncytial virus was more frequent in children under 2 years and in severe pneumonia. Tuberculosis was diagnosed in 2.3% of children. IS was the most useful specimen to identify the etiology (33.6%), and blood cultures were positive in 3.6%. The concordance between all available diagnostic tests was low. A high percentage of healthy children were colonized by S. pneumoniae and Haemophilus influenzae, or were infected by Parainfluenza, Rhinovirus, Influenza and Adenovirus.ConclusionsRespiratory viruses are the most frequent etiology of CAP in children and adolescents, in particular in those under 5 years. This study shows the challenges in making an etiologic diagnosis of CAP in pediatric population because of the poor concordance between tests and the high percentage of multiple microorganisms in healthy children. IS is useful for CAP diagnosis in pediatric population.

Project description:BackgroundIncidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.MethodsWe conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists.ResultsFrom January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%).ConclusionsThe burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

Project description:BackgroundVirus, particularly respiratory tract virus infection is likely to co-occur in children with community-acquired pneumonia (CAP). Study focusing on the association between common viruses coinfection and children with CAP is rare. We aimed to study the association between seven common viruses coinfection and clinical/laboratory indexes in children with CAP.MethodsSix hundred and eighty-four CAP cases from our hospital were enrolled retrospectively. Seven common viruses, including influenza A (FluA), influenza B (FluB), human parainfluenza virus (HPIV), Esptein-Barr virus (EBV), coxsackie virus (CoxsV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were investigated for their associations with CAP. We analyzed the differences of hospitalization days, white blood cell (WBC), c-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), urine red blood cell (uRBC), blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CKMB) among different viruses coinfection groups by using one-way ANOVA analysis. The differences of clinical/laboratory indexes between ordinary and severe pneumonia groups, as well as non-virus vs multi co-infection viruses groups, and single vs multi co-infection viruses groups by using independent samples T test. Receiver operating characteristic (ROC) curve analyses were applied to test the the predictive value of the clinical/laboratory parameters for the risk of viruses coinfections among CAP. Binary logistic analysis was performed to test the association between various indexes and viruses co-infection.ResultsEighty-four multiple viruses coinfections yielded different prognosis compared with that in 220 single virus coinfection. CMV coinfection was associated with longest hospitalization days, highest ALT, AST and CKMB level. HSV coinfection was associated with highest WBC count, CRP, ESR, and BUN. EBV coinfection was associated with highest PLT and PCT level. FluB coinfection was associated with highest Scr level. CoxsV coinfection was associated with highest uRBC, LDH and CK level. ROC curve analyses showed that CK had the largest area under the curve (AUC: 0.672, p < 10-4) for the risk of viruses coinfections risk in CAP. Significant association between PLT, uRBC, BUN, CK, and CKMB and virus coinfection risk in CAP was observed.ConclusionsMultiple viruses coinfections indicated different prognosis. Different viruses coinfection yielded varying degrees of effects on the cardiac, liver, kidney and inflamatory injury in CAP. The alterations of clinical/laboratory parameters, particularly CK may be associated with the risk of viruses coinfections in CAP.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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