Ceftolozane/Tazobactam May Be New Tx Option for Complicated Pyelonephritis

SAN DIEGO, CA—The combination of ceftolozane and tazobactam showed comparable outcomes to levofloxacin in the treatment of complicated pyelonephritis, according to results from the Phase 3 ASEPCT-cUTI trial presented at IDWeek 2015.

“Clinical cure rates for ceftolozane/tazobactam and levofloxacin were high for patients with complicated pyelonephritis and for those with uncomplicated pyelonephritis,” reported lead study author Daniel Cloutier, PharmD, from Merck & Co., Inc., in Kenilworth, NJ. “Ceftolozane/tazobactam displayed potent activity against CTX-M-14/15-positive E. coli.

Ceftolozane/tazobactam composite cure rates “were similar to those of levofloxacin in the subgroup of patients with complicated pyelonephritis; in patients with uncomplicated pyelonephritis, ceftolozane/tazobactam showed a significantly higher composite cure rate relative to levofloxacin,” Dr. Cloutier noted.

Rates of pathogen eradication were lower in patients with complicated pyelonephritis in both of the study's treatment groups, he noted.

Dr. Cloutier and colleagues performed a post hoc analysis to evaluate the efficacy of ceftolozane/tazobactam vs. levofloxacin in the subset of patients with complicated pyelonephritis in the Phase 3 ASPECT-cUTI program. Patients aged ≥18 years with complicated urinary lower tract infections (UTIs) or pyelonephritis were randomized to intravenous (IV) ceftolozane/tazobactam 1.5g every 8 hours or IV levofloxacin 750mg daily for 7 days. Complicated infections included infection in the presence of an indwelling catheter or structural or functional urinary tract abnormality, Dr. Cloutier noted.

The study's primary outcome was composite cure (microbiological eradiation and clinical cure) at the test-of-cure (TOC) visit 5–9 days post-therapy in the microbiological modified intent-to-treat (mMITT; n=800) and microbiologically evaluable (ME) populations. Of the 800 patients in the mMITT population, 656 (82%) had pyelonephritis of which 115 (17.5%) occurred in the presence of a complicating factor.

Levofloxacin-resistant baseline uropathogens were isolated in 29.3% and 35.1% of patients in the ceftolozane/tazobactam and levofloxacin treatment arms, respectively, Dr. Cloutier reported.

Ceftolozane/tazobactam demonstrated comparable composite cure rates to levofloxacin in the mMITT and ME populations. Composite cure in the mMITT population was 58.6% in the ceftolozane/tazobactam group vs. 57.9% in the levofloxacin group for complicated pyelonephritis (treatment difference 0.7%; 95% CI: -16.8 to 18.19), and 83.3% vs. 76.4% for uncomplicated pyelonephritis (treatment difference 6.9%; 95% CI: 0.18, 13.66). Composite cure in the ME population was 63.8% in the ceftolozane/tazobactam group vs. 65.3% in the levofloxacin group for complicated pyelonephritis (treatment difference -1.5%; 95% CI: -19.99 to 17.09), and 89.7% vs. 84.0%, respectively, for uncomplicated pyelonephritis (treatment difference 5.7; 95% CI: -0.42, 11.84).

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