title: Ecological impact of MCB3837 on the normal human microbiota.
abstract: MCB3837 is a novel, water-soluble, injectable prodrug that is rapidly converted to the active substance MCB3681 in vivo following intravenous (i.v.) administration. Both MCB3837 and MCB3681 are oxazolidinone-quinolone hybrid molecules. The purpose of the present study was to investigate the effect of MCB3681 on the human skin, nose, oropharyngeal and intestinal microbiota following administration of MCB3837. Twelve healthy male subjects received i.v. MCB3837 (6 mg/kg body weight) once daily for 5 days. Skin, nose, saliva and faecal samples were collected on Day -1 (pre dose), during administration on Days 2 and 5, and post dose on Days 8, 12 and 19. Micro-organisms were identified to genus level. No measurable concentrations of MCB3681 were found in any saliva samples or in the faecal samples on Day -1. On Day 2, 10 volunteers had faecal MCB3681 concentrations between 16.5 mg/kg faeces and 275.1mg/kg faeces; no MCB3681 in faeces could be detected in two of the volunteers. On Day 5, all volunteers had faecal concentrations of MCB3681 ranging from 98.9 to 226.3 mg/kg. MCB3681 caused no ecological changes in the skin, nasal and oropharyngeal microbiota. The numbers of enterococci, bifidobacteria, lactobacilli and clostridia decreased in the intestinal microbiota during administration of the drug. Numbers of Escherichia coli, other enterobacteria and Candida were not affected during the study. There was no impact on the number of Bacteroides. The faecal microbiota was normalised on Day 19. No new colonising aerobic or anaerobic Gram-positive bacteria with MCB3681 minimum inhibitory concentrations of ≥4 mg/L were found.
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Mamun-Ur
authors.initials: MU
authors.lastname: Rashid
authors.affiliation: University Medical Center Schleswig-Holstein, Institute for Infection Medicine, Brunswiker Str. 4, D-24105 Kiel, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Dalhoff
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäckström
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Björkhem-Bergman
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Georgios
authors.initials: G
authors.lastname: Panagiotidis
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Andrej
authors.initials: A
authors.lastname: Weintraub
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden. Electronic address: carl.erik.nord@ki.se.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001419:Bacteria / Q000145:classification / Q000187:drug effects*; D002175:Candida / Q000145:classification / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000382:microbiology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008828:Microbiological Techniques; D064307:Microbiota / Q000187:drug effects*; D009296:Nasal Cavity / Q000382:microbiology; D009960:Oropharynx / Q000382:microbiology; D023303:Oxazolidinones / Q000008:administration & dosage*; D011355:Prodrugs / Q000008:administration & dosage*; D015363:Quinolones / Q000008:administration & dosage*; D012867:Skin / Q000382:microbiology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D011355:Prodrugs; D015363:Quinolones
keywords: MCB3681; MCB3837; Normal human microbiota