PHILADELPHIA, PA—Ceftolozane/tazobactam demonstrated superior efficacy compared with levofloxacin in patients with complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens, a study reported at IDWeek 2014.

 Ceftolozane/tazobactam demonstrated significantly higher composite cure rates and per-pathogen microbiological eradication rates for Enterobacteriaceae, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa versus levofloxacin in the microbiological modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations, reported George Sakoulas, MD, from the Department of Pediatrics, University of California San Diego School of Medicine, San Diego, CA, and colleagues from Cubist Pharmaceuticals, Lexington, MA.

The study pooled efficacy data from the Phase 3 randomized controlled double-blind ASPECT (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam)-cUTI trial. Before the availability of susceptibility data, hospitalized patients ≥18 years old who had pyuria and clinical symptoms of cUTI were randomized to receive intravenous ceftolozane/tazobactam (1.5g every 8 hours) or intravenous levofloxacin (750mg daily for 7 days). The primary outcome was the composite microbiological eradication and clinical cure (composite cure) rate at the test-of-cure visit, 5–9 days after the end of therapy in both the mMITT and ME populations. 

Of the1,083 patients enrolled, 800 (74%) were included in the mMITT population. Among these patients, 212 (26.5%) had levofloxacin-resistant uropathogens at baseline (100 in the ceftolozane/tazobactam arm and 112 in the levofloxacin arm), the majority of which were E. coli; 176 (83%) were susceptible to ceftolozane/tazobactam and 93 (43.8%) were also extended-spectrum β-lactamase producers.

Overall composite favorable response rate by baseline diagnosis in patients with levofloxacin-resistant uropathogens was 60% in the ceftolozane/tazobactam arm and 39.3% in the levofloxacin arm.

When compared with the general study population, composite cure rates were lower for both treatment arms, suggesting that “levofloxacin resistance is an independent predictor of microbiological, and thus composite, failure,” Dr. Sakoulas noted. “These data demonstrate that high urine concentrations achieved with high-dose levofloxacin are not sufficient to overcome levofloxacin resistance.”

He concluded, “ceftolozane/tazobactam offers an alternative treatment for cUTI in settings of increasing fluoroquinolone resistance among common uropathogens.”