Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis

Abstract

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.

The Antibiotic Drug Tigecycline: A Focus on its Promising Anticancer Properties

“…Studies have indicated that TIG exhibits broad spectrum anti-bacterial ability against Gram-positive and Gram-negative bacteria, including Staphylococcus aureus (Sader et al, 2016), Acinetobacter baumannii (Rao et al, 2016), Enterobacteriaceae (Thaden et al, 2016), among others. As an expanded-spectrum antibiotic, TIG is clinically available for bacterial eradication with a good safety and tolerability profile, particularly for cancer patients (Lauf et al, 2014). Because of intensive myelosuppressive chemotherapy (Razzouk et al, 2006) and surgical site infections, cancer patients are susceptible to infections (Teillant et al, 2015).…”

Do Diabetic Foot Infections With Methicillin-ResistantStaphylococcus aureusDiffer From Those With Other Pathogens?

“…Likewise, a growing body of literature has highlighted the fact that a high minimal inhibitory concentration (MIC) of MRSA strains for vancomycin adversely affects remission in bacteremia 22 or localized osteoarticular infections. 23 These concerns have spurred the development and more widespread use of newer anti-MRSA molecules, such as linezolid, daptomycin, 24,25 tigecycline, 26 ceftaroline, oritavancin, televancin, and dalbavancin. 27 Over the past 15 years, MRSA infection has become a major concern in patients with DFI.…”

Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs

“…Clinical success rates were significantly lower in patients with HAPs and DFIs. This discrepancy is probably due to inclusion of up-to-date published data (16,19,20,24,26) in our meta-analysis, resulting from an updated search of databases. The inferiority of tigecycline may be explained to some extent by the following aspects.…”