title: Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections.
abstract: Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece; Department of Internal Medicine - Infectious Diseases, Mitera Hospital, Hygeia Group, Athens, Greece; Tufts University School of Medicine, Boston, MA, USA. Electronic address: m.falagas@aibs.gr.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Falagas
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece; Department of Internal Medicine - Infectious Diseases, Mitera Hospital, Hygeia Group, Athens, Greece.
authors.forename: Konstantinos Z
authors.initials: KZ
authors.lastname: Vardakas
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Tsiveriotis
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece; Department of Internal Medicine - Infectious Diseases, Mitera Hospital, Hygeia Group, Athens, Greece.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Triarides
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.
authors.forename: Giannoula S
authors.initials: GS
authors.lastname: Tansarli
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016638:Critical Illness; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D000078304:Tigecycline; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline
keywords: Acinetobacter; Enterobacteriaceae; Intensive care unit; MDR; PDR; XDR