title: Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota.
abstract: Ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on day -1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14, and 21. Escherichia coli numbers decreased during the study and normalized on day 21. An increased number of Klebsiella bacteria appeared on day 14 and normalized on day 21. The number of other enterobacteria decreased during the study, and the number of enterococci decreased from days 2 to 7 and normalized on day 9. Candida numbers increased from days 5 to 9 and normalized after day 14. The number of lactobacilli decreased during the study and recovered on day 14. The number of bifidobacteria decreased on day 2 and normalized on day 21. The number of Bacteroides bacteria was unchanged. Clostridium difficile numbers decreased on days 7 and 9 and increased on days 14 and 21. A toxigenic C. difficile strain was detected in one volunteer on day 21 with no reported adverse events. Plasma samples were collected on days -1, 2, 5, and 7. Ceftaroline and avibactam concentrations were 0 to 34.5 mg/liter and 0 to 61.6 mg/liter, respectively, in plasma and 0 to 35.4 mg/kg and 0 to 98.5 mg/kg, respectively, in feces. (This study is registered in the European Clinical Trials Database [https://eudract.ema.europa.eu/] under number EudraCT 2012 004921-25.).
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mamun-Ur
authors.initials: MU
authors.lastname: Rashid
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Rosenborg
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Georgios
authors.initials: G
authors.lastname: Panagiotidis
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Söderberg-Löfdal
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrej
authors.initials: A
authors.lastname: Weintraub
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden carl.erik.nord@ki.se.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D055815:Young Adult; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology; D047090:beta-Lactams / Q000494:pharmacology; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000097583:Ceftaroline; C543519:avibactam