Safety and efficacy of intravenous doripenem for the treatment of complicated urinary tract infections and pyelonephritis.

Doripenem was evaluated in adults with complicated urinary tract infections and pyelonephritis in two phase 3 studies. DORI-05, a randomized, double-blind study compared doripenem 500 mg every 8 hours with levofloxacin 250 mg every 24 hours. DORI-06 was a single-arm study designed to confirm the doripenem response in DORI-05. 799 received doripenem, 372 levofloxacin. Microbiological eradication rates in microbiologically evaluable populations were 82.8% for doripenem, 83.4% for levofloxacin (Δ: -0.6%; 95% confidence interval: -6.4, 5.2), and 80.9% and 78.2%, respectively (Δ: 2.7%; 95% confidence interval: -3.0, 8.3) in the co-primary microbiologically modified intent-to-treat populations. Clinical cure rates in the clinically evaluable populations were 94.1% for doripenem, 90.2% for levofloxacin (Δ: 3.9%; 95% confidence interval: -0.5, 8.2). In subjects infected with levofloxacin- resistant Escherichia coli, outcomes were statistically significantly greater with doripenem. Genotyping data indicate persistent E. coli infections were often due to infection with new strains. Doripenem was generally found to be safe and well tolerated.ClinicalTrials.gov registration numbers: DORI-05 = NCT00229021, DORI-06 = NCT00210990.