The polymicrobial nature of complicated
intra-abdominal infections makes these
infections particularly challenging to treat. The initial selection of antimicrobial
therapy is therefore extremely important. Inappropriate empiric antimicrobial
therapy has been shown to delay clinical resolution, increase length of
hospital stay, and increase the risk of mortality. In addition, the increasing frequency with which resistant isolates (e.g., extended spectrum
beta-lactamases [ESBLs]) are recovered from patients mandates that empiric antimicrobial
therapy covers these difficult-to-treat organisms. Here, we assessed the efficacy of a new
antimicrobial agent,
tigecycline. This is a combined analysis of data from the European sites that participated in two Phase III, double-blind trials to evaluate the efficacy and safety of
tigecycline, versus that of
imipenem/cilastatin, in adults with complicated
intra-abdominal infections. Patients received either
tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 hours) or
imipenem/cilastatin (500/500 mg intravenously every 6 hours) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-44 days after
therapy) in the co-primary microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations. For the ME group, clinical cure rates at the test-of-cure visit were 92.4% (219/237) for
tigecycline versus 88.8% (198/223) for
imipenem/cilastatin (95% CI = -2.2, 9.4). Clinical cure rates for the mmITT populations were 87.3% (247/283) for
tigecycline versus 83.5% (228/273) for
imipenem/cilastatin (95% CI = -2.5, 10.0) at the test-of-cure visit. Pretherapy in vitro activity against baseline isolates for
tigecycline and
imipenem/cilastatin were also determined. The mean MIC(90) for
tigecycline against the most commonly isolated aerobes and anaerobes was < or =2.0 microg/mL. No pretherapy isolates displayed resistance to
tigecycline based on the breakpoints used. Bacterial susceptibilities to
tigecycline appeared to be consistent with clinical responses. Most commonly reported treatment emergent adverse events for
tigecycline and
imipenem/cilastatin were
nausea (14.7% and 11.8%, respectively, p = 0.267) and
vomiting (10.7% and 7.3%, respectively p = 0.146). This combined analysis demonstrates that
tigecycline is safe and effective for the treatment of complicated
intra-abdominal infections, and reflects the findings of the global population.