A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae

Abstract

To evaluate the efficacy and safety of tigecycline in patients with selected serious infections caused by resistant Gram-negative bacteria, or failures who had received prior antimicrobial therapy or were unable to tolerate other appropriate antimicrobials. Secondary objectives included an evaluation of the microbiological efficacy of tigecycline and in vitro activity of tigecycline for resistant Gram-negative bacteria. This open-label, Phase 3, non-comparative, multicentre study assessed the efficacy and safety of intravenous tigecycline (100 mg initially, then 50 mg 12 hourly for 7-28 days) in hospitalized patients with serious infections including complicated intra-abdominal infection; complicated skin and skin structure infection (cSSSI); community-acquired pneumonia (CAP); hospital-acquired pneumonia, including ventilator-associated pneumonia; or bacteraemia, including catheter-related bacteraemia. All patients had infections due to resistant Gram-negative organisms, including extended-spectrum beta-lactamase-producing strains, or had failed on prior therapy or could not receive (allergy or intolerance) one or more agents from three classes of commonly used antibiotics. The primary efficacy endpoint was clinical response in the microbiologically evaluable (ME) population at test of cure (TOC). Safety data included vital signs, laboratory tests and adverse events (AEs). In the ME population at TOC, the clinical cure rate was 72.2% [95% confidence interval (CI): 54.8-85.8], and the microbiological eradication rate was 66.7% (95% CI: 13.7-78.8). The most commonly isolated resistant Gram-negative pathogens were Acinetobacter baumannii (47%), Escherichia coli (25%), Klebsiella pneumoniae (16.7%) and Enterobacter spp. (11.0%); the most commonly diagnosed serious infection was cSSSI (67%). The most common treatment-emergent AEs were nausea (29.5%), diarrhoea (16%) and vomiting (16%), which were mild or moderate in severity. In this non-comparative study, tigecycline appeared safe and efficacious in patients with difficult-to-treat serious infections caused by resistant Gram-negative organisms.