title: Ecological Effect of Solithromycin on Normal Human Oropharyngeal and Intestinal Microbiota.
abstract: Solithromycin is a new fluoroketolide. The purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. Thirteen healthy volunteers (median age, 27.3 years) received oral solithromycin at 800 mg on day 1 followed by 400 mg daily on days 2 to 7. Fecal and saliva samples were collected at baseline and on days 2, 5, 7, 9, 14, and 21 for pharmacokinetic and microbiological analyses. Plasma samples were collected predose on days 2, 5, and 7 as proof of exposure, and solithromycin concentration ranges were 21.9 to 258 ng/ml, 18.0 to 386 ng/ml, and 16.9 to 417 ng/ml, respectively. The solithromycin concentrations in feces were 15.8 to 65.4 mg/kg, 24.5 to 82.7 mg/kg, 21.4 to 82.7 mg/kg, 12.1 to 72.4 mg/kg, 0.2 to 25.6 mg/kg, and 0 to 0.5 mg/kg on days 2, 5, 7, 9, 14, and 21, respectively. The numbers of enterobacteria and enterococci decreased and were normalized on day 14. The numbers of lactobacilli and bifidobacteria decreased from day 2 to day 14 and were normalized on day 21. The clostridia decreased on days 2, 7, and 14 and were normalized on day 21. No Clostridium difficile strains or toxins were detected during the study period. The number of Bacteroides strains was not significantly changed. The solithromycin concentrations in saliva were 0 to 1.2 mg/liter, 0 to 0.5 mg/liter, 0 to 0.5 mg/liter, and 0 to 0.1 mg/liter on days 2, 5, 7, and 9, respectively. The numbers of streptococci decreased on day 2 and were normalized on day 5. The numbers of lactobacilli, prevotellae, fusobacteria, and leptotrichiae decreased from day 2 and were normalized on day 21.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mamun-Ur
authors.initials: MU
authors.lastname: Rashid
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Rosenborg
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Georgios
authors.initials: G
authors.lastname: Panagiotidis
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Holm
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Söderberg Löfdal
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden andrej.weintraub@ki.se.
authors.forename: Andrej
authors.initials: A
authors.lastname: Weintraub
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001644:Bifidobacterium / Q000187:drug effects; D016360:Clostridioides difficile / Q000187:drug effects; D016983:Enterococcus / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D005260:Female; D045182:Fusobacteria / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D045183:Leptotrichia / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D064307:Microbiota / Q000187:drug effects*; D009960:Oropharynx / Q000382:microbiology*; D018720:Prevotella / Q000187:drug effects; D012463:Saliva / Q000382:microbiology; D013291:Streptococcus / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin