{"entity": "researcher", "timestamp": "2026-08-08T04:15:14.925Z", "family": "Dooley", "given": "Kelly E", "initials": "KE", "orcid": "0000-0001-9013-5256", "affiliations": ["Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c918050f966e4cfcb761ee822918b894.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c918050f966e4cfcb761ee822918b894"}}, "publications": [{"entity": "publication", "iuid": "65b98d5189d04495861c32b42ad11e50", "links": {"self": {"href": "https://publications.scilifelab.se/publication/65b98d5189d04495861c32b42ad11e50.json"}, "display": {"href": "https://publications.scilifelab.se/publication/65b98d5189d04495861c32b42ad11e50"}}, "title": "Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis: The COMRADE Randomized, Phase 2A Clinical Trial.", "authors": [{"family": "De Jager", "given": "Veronique", "initials": "V", "orcid": "0000-0001-6389-5575", "researcher": {"href": "https://publications.scilifelab.se/researcher/e773047b1ab54376a335e2571c44d971.json"}}, {"family": "Gupte", "given": "Nikhil", "initials": "N"}, {"family": "Nunes", "given": "Silvia", "initials": "S"}, {"family": "Barnes", "given": "Grace L", "initials": "GL"}, {"family": "van Wijk", "given": "Rob Christiaan", "initials": "RC", "orcid": "0000-0001-7247-1360", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae6d15792b974a20adf6ad6efcb4d6d2.json"}}, {"family": "Mostert", "given": "Joni", "initials": "J"}, {"family": "Dorman", "given": "Susan E", "initials": "SE"}, {"family": "Abulfathi", "given": "Ahmed A", "initials": "AA"}, {"family": "Upton", "given": "Caryn M", "initials": "CM"}, {"family": "Faraj", "given": "Alan", "initials": "A"}, {"family": "Nuermberger", "given": "Eric L", "initials": "EL"}, {"family": "Lamichhane", "given": "Gyanu", "initials": "G"}, {"family": "Svensson", "given": "Elin M", "initials": "EM", "orcid": "0000-0002-0093-6445", "researcher": {"href": "https://publications.scilifelab.se/researcher/f670a6b6bfe147429830547702a56bb6.json"}}, {"family": "Simonsson", "given": "Ulrika S H", "initials": "USH", "orcid": "0000-0002-3424-9686", "researcher": {"href": "https://publications.scilifelab.se/researcher/653eb745f8e847d0b4bac44bba7dec4d.json"}}, {"family": "Diacon", "given": "Andreas H", "initials": "AH"}, {"family": "Dooley", "given": "Kelly E", "initials": "KE", "orcid": "0000-0001-9013-5256", "researcher": {"href": "https://publications.scilifelab.se/researcher/c918050f966e4cfcb761ee822918b894.json"}}], "type": "clinical trial, phase ii", "published": "2022-05-15", "journal": {"title": "Am. J. Respir. Crit. Care Med.", "issn": "1535-4970", "volume": "205", "issue": "10", "pages": "1228-1235", "issn-l": "1073-449X"}, "abstract": "Rationale: Carbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain. Objectives: To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin. Methods: Individuals with drug-sensitive pulmonary tuberculosis were randomized to one of four intravenous meropenem-based arms: 2 g every 8 hours (TID) (arm C), 2 g TID plus rifampin at 20 mg/kg once daily (arm D), 1 g TID (arm E), or 3 g once daily (arm F). All participants received amoxicillin/clavulanate with each meropenem dose. Serial overnight sputum samples were collected from baseline and throughout treatment. Median daily fall in colony-forming unit (CFU) counts per milliliter of sputum (solid culture) (EBACFU0-14) and increase in time to positive culture (TTP) in liquid media were estimated with mixed-effects modeling. Serial blood samples were collected for pharmacokinetic analysis on Day 13. Measurements and Main Results: Sixty participants enrolled. Median EBACFU0-14 counts (2.5th-97.5th percentiles) were 0.22 (0.12-0.33), 0.12 (0.057-0.21), 0.059 (0.033-0.097), and 0.053 (0.035-0.081); TTP increased by 0.34 (0.21-0.75), 0.11 (0.052-0.37), 0.094 (0.034-0.23), and 0.12 (0.04-0.41) (log10 h), for arms C-F, respectively. Meropenem pharmacokinetics were not affected by rifampin coadministration. Twelve participants withdrew early, many of whom cited gastrointestinal adverse events. Conclusions: Bactericidal activity was greater with the World Health Organization-recommended total daily dose of 6 g daily than with a lower dose of 3 g daily. This difference was only detectable with solid culture. Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens. Clinical trial registered with www.clinicaltrials.gov (NCT03174184).", "doi": "10.1164/rccm.202108-1976OC", "pmid": "35258443", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "ClinicalTrials.gov", "key": "NCT03174184"}], "notes": [], "created": "2022-11-09T15:42:25.879Z", "modified": "2024-01-16T13:48:36.515Z"}]}