Intravenous Doripenem at 500 Milligrams versus Levofloxacin at 250 Milligrams, with an Option To Switch to Oral Therapy, for Treatment of Complicated Lower Urinary Tract Infection and Pyelonephritis

Abstract

The prospective, multicenter, double-blind study presented in this report evaluated whether or not intravenous (IV) administration of doripenem, a carbapenem with bactericidal activity against gram-negative and gram-positive uropathogens, is inferior to IV administration of levofloxacin in the treatment of complicated urinary tract infection (cUTI). Patients (n ‫؍‬ 753) with complicated lower UTI or pyelonephritis were randomly assigned to receive IV doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients in both treatment arms were eligible to switch to oral levofloxacin after 3 days of IV therapy to complete a 10-day treatment course if they demonstrated significant clinical and microbiological improvements. The microbiological cure rate (primary end point) was determined at the test-of-cure (TOC) visit occurring 5 to 11 days after the last dose of antibiotic. For the microbiologically evaluable patients (n ‫؍‬ 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, ؊8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n ‫؍‬ 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were generally well tolerated. Doripenem was found not to be inferior to levofloxacin in terms of therapeutics and is now approved for use in the United States and Europe for the treatment of adults with cUTI, including pyelonephritis. As fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs, including treatment of pyelonephritis.

Worldwide Experience with the Use of Doripenem against Extended-Spectrum-β-Lactamase-Producing and Ciprofloxacin-Resistant Enterobacteriaceae : Analysis of Six Phase 3 Clinical Studies

“…For treatment of cUTI, doripenem and levofloxacin were very effective against Enterobacteriaceae overall. However, cure rates were higher for doripenem for ESBL and CIPRE, suggesting that as fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs (7).…”

A Review of Doripenem for the Treatment of Serious Bacterial Infections

“…113,114 The total duration of therapy was 10 days and could be extended to 14 days in patients with bacteremia. After 3 days of IV study drug, patients in either treatment group had the option to switch to oral levofloxacin (250 mg q24h) if no fever was present for at least 24 hours, signs and symptoms of cUTI were absent or improved from baseline, and at least 1 urine culture showed no growth or a colony count of ,10 4 CFU/mL and no subsequent cultures grew a uropathogen at $10 4 CFU/mL.…”

“…113,114 In the first study, a prospective, randomized, double-blind design was implemented to determine the effect of IV doripenem (500 mg q8h by 1-hour infusion) compared with IV levofloxacin (250 mg q24h by 1-hour infusion). 113 The second study was a noncomparative study that tested doripenem (500 mg q8h by 1-hour infusion) with the levofloxacin comparator arm of the first study.…”

The Clinical Guidelines for Acute Uncomplicated Cystitis and Acute Uncomplicated Pyelonephritis

“…Urinalysis or urine culture for follow-up in asymptomatic 0.5 g tid Naber et al [47] Bid: twice a day, qd: once a day, tid: three times a day, Co-amoxiclav: amoxicillin-clavulanic acid. a) Lower dose studied, but higher dose recommended by experts, b) not studied as monotherapy in acute uncomplicated pyelonephritis, c) mainly for Gram-positive pathogens, d) same protocol for acute uncomplicated pyelonephritis and complicated urinary tract infection.…”