Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis.
A phase 3, randomized, double-blind trial was conducted in subjects with diabetic foot infections without osteomyelitis (primary study) or with osteomyelitis (substudy) to determine the efficacy and safety of parenteral (intravenous [iv]) tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem ± vancomycin. Among 944 subjects in the primary study who received ≥1 dose of study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.5% of tigecycline- and 82.5% of ertapenem ± vancomycin-treated subjects were cured. Corresponding rates for the clinical modified intent-to-treat population were 71.4% and 77.9%, respectively. Clinical cure rates in the substudy were low (<36%) for a subset of tigecycline-treated subjects with osteomyelitis. Nausea and vomiting occurred significantly more often after tigecycline treatment (P = 0.003 and P < 0.001, respectively), resulting in significantly higher discontinuation rates in the primary study (nausea P = 0.007, vomiting P < 0.001). In the primary study, tigecycline did not meet criteria for noninferiority compared with ertapenem ± vancomycin in the treatment of subjects with diabetic foot infections.
Department of General Surgery, Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Budapest, Hungary. Electronic address: drlauf@freemail.hu.
Laszlo
L
Lauf
Department of Infectology, St. George County Hospital, Szekesfehervar, Hungary.
Zsófia
Z
Ozsvár
Benmed Park Clinic, Benoni, Johannesburg, South Africa.
Ismael
I
Mitha
Third Department of Surgery, Semmelweis University, Budapest, Hungary.
Janos
J
Regöly-Mérei
Section of Infectious Diseases, Department of Medicine, University of Manitoba, Manitoba, Canada.
John M
JM
Embil
Pfizer, Inc, Collegeville, PA, USA.
Angel
A
Cooper
Pfizer, Inc, Collegeville, PA, USA.
Mary Beth
MB
Sabol
Pfizer, Inc, Paris, France.
Nathalie
N
Castaing
Pfizer, Inc, Paris, France.
Nathalie
N
Dartois
Pfizer, Inc, Collegeville, PA, USA.
Jean
J
Yan
Pfizer, Inc, Collegeville, PA, USA.
Gary
G
Dukart
Pfizer, Inc, Collegeville, PA, USA.
Robert
R
Maroko
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017719:Diabetic Foot / Q000150:complications* / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D000077727:Ertapenem; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D010019:Osteomyelitis / Q000188:drug therapy*; D000078304:Tigecycline; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000453:epidemiology; D055815:Young Adult; D047090:beta-Lactams / Q000009:adverse effects / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline; D000077727:Ertapenem
Diabetic foot infections; Ertapenem; Osteomyelitis; Tigecycline; Vancomycin