title: Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials.
abstract: An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies).
authors.affiliation: Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy. Electronic address: mattba@tin.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.affiliation: Clinical Affairs, Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: McGovern
authors.affiliation: Medical Department of Infection and Tropical Medicine, Kaiser Franz Josef Hospital, Kundratstraße 3, 1100 Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wenisch
authors.affiliation: Biostatistics, Pfizer Inc., 558 Eastern Point Road, Groton, CT 06340, USA.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Meyer
authors.affiliation: Biostatistics, Pfizer Inc., 558 Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Jean Li
authors.initials: JL
authors.lastname: Yan
authors.affiliation: Biostatistics, Pfizer Inc., 558 Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Wible
authors.affiliation: Clinical Affairs, Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Rottinghaus
authors.affiliation: Medicines Development Group, Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Quintana
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D017327:Clinical Trials, Phase IV as Topic; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000453:epidemiology / Q000401:mortality; D017192:Skin Diseases, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018461:Soft Tissue Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D000078304:Tigecycline; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline
keywords: All-cause; Glycylcycline; Mortality; Risk factor; Tigecycline