The Efficacy and Safety of Tigecycline in the Treatment of Skin and Skin‐Structure Infections: Results of 2 Double‐Blind Phase 3 Comparison Studies with Vancomycin‐Aztreonam

Abstract

Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%-83.1%) versus 81.9% (95% CI, 78.3%-85.1%) (P = .4183); and clinically evaluable, 86.5% (95% CI, 82.9%-89.6%) versus 88.6% (95% CI, 85.1%-91.5%) (P = .4233). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

“…11 It had efficacy similar to that of vancomycin plus aztreonam in 2 phase 3, doubleblind pivotal studies in 1116 hospitalized adults with cSSSIs. 91 Tigecycline had a safety profile similar to that of vancomycin-aztreonam, but nausea and vomiting were more common (46% and 21%, respectively; P<.001). Recently, the FDA issued a boxed warning for increased all-cause mortality with tigecycline treatment when used in approved indications.…”

Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic Tigecycline

“…TG inhibits translation of bacterial proteins by binding both small and large ribosomal subunits of bacterial ribosomes (39)(40)(41)(42).…”

Validation and Reproducibility Assessment of Tigecycline MIC Determinations by Etest

“…Tigecycline was recently approved worldwide for use in patients with complicated skin and skin structure infections and complicated intra-abdominal infections. The broad spectrum of activity of tigecycline against gram-negative and gram-positive pathogens matched that seen with classical tetracyclines (1,4,9,13). However, in contrast to the classical tetracyclines, tigecycline was not subject to efflux through the tetracycline specific efflux pumps or affected by the ribosomal protection mechanism of tetracycline resistance (11,14,18).…”