Tigecycline Monotherapy vs. Imipenem/Cilastatin in Hospitalized Chinese Patients with cIAIs

Background

The management of complicated intra-abdominal infections (cIAIs) remains a challenge to physicians because of their polymicrobial nature coupled with the high risk of sequelae and mortality in severely ill patients with these infections. Tigecycline, a first-in-class expanded broad-spectrum glycylcycline antibiotic approved for use in patients with cIAIs, overcomes the 2 major mechanisms of resistance to tetracycline.

Aim

To evaluate safety and efficacy of tigecycline monotherapy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs

Patients Profile

• Men and non-pregnant, non-lactating women ≥18 years of age who required a surgical procedure for a complicated intra-abdominal infection (cIAI)
• cIAI defined as the following:

• An intra-abdominal abscess (including liver and spleen) that developed in a postsurgical patient after receiving standard antibacterial therapy (i.e., at least 48 hours, but not more than 5 days of antibiotics)
• Appendicitis complicated by perforation and/or a periappendiceal abscess
• Perforated diverticulitis complicated by abscess formation or fecal contamination
• Complicated cholecystitis with evidence of perforation or empyema
• perforation of a gastric or duodenal ulcer with symptoms exceeding 24 hours
• Purulent peritonitis or peritonitis associated with fecal contamination
• Perforation of the large or small intestine with abscess or fecal contamination, or traumatic bowel perforation with symptoms lasting at least 12 hours before an operation

Methods

Study Design

• Phase 3
• Multicenter
• Open-label study
• Patients (N=199) were randomly (1:1) assigned to receive IV tigecycline (n=97) or imipenem/cilastatin (n=102) for ≤2 weeks

Interventions

• Tigecycline: initial 100-mg dose given by intravenous [IV] infusion

over a 30-minute period, followed by 50 mg IV every 12 hours

• IV imipenem/cilastatin: :500 mg/500 mg every 6 hours or dose-adjusted based on weight and creatinine clearance

Study Endpoints

• Clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat (m-mITT) and microbiologically evaluable (ME) populations

• Microbiological response at the TOC visit by patient and isolate was performed as a secondary analysis

Results

Clinical Efficacy

• Tigecycline-treated patients with polymicrobial infection tended to have lower clinical cure rates compared with patients who had monomicrobial infection

• Tigecycline was effective across the range of clinical diagnoses.
  • Clinical cure rates at the TOC visit for the ME population were 87.0% for tigecycline and 100.0% for imipenem/cilastatin

Microbial Efficacy

• In the ME population, the baseline organisms were eradicated in 86.5% of tigecycline-treated patients and 97.9% of patients treated with imipenem/cilastatin at the TOC visit
• For E. coli, the most commonly isolated bacteria, eradication rates were 88.1% for tigecycline vs. 97.7% for imipenem/ cilastatin
• Overall, MIC values for tigecycline against the most commonly isolated aerobes and anaerobes was ≤2.0 ?g/mL
  • For E.coli , MIC50 and MIC90 values were 0.125 ?g/mL and 0.5 ?g/mL for tigecycline, respectively, and 0.25 ?g/mL and 0.5 ?g/mL for imipenem/cilastatin, respectively

Safety

• Tigecycline monotherapy was generally well tolerated in this study population
• The overall incidence of treatment-emergent AEs was significantly higher after tigecycline therapy (80.4%) compared with imipenem/cilastatin (53.9%; P < 0.001).
  • gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005)

Conclusions

• Tigecycline monotherapy appears to be both effective and safe for the treatment of cIAI in Chinese patients
• Clinical cure rates and safety profile for tigecycline were consistent with those found in global cIAI studies
• Digestive-related adverse events were significantly higher in the tigecycline group, especially nausea and vomiting

Reference

BMC Infectious Diseases 2010 10:217.