The investigational antibiotic combination ceftolozane/tazobactam did as well as a standard drug in treating complicated urinary tract infections, according to the company developing the drug.
In two, randomized, multicenter clinical trials, the drug combination met both European and U.S. criteria for noninferiority to levofloxacin (Levaquin), Cubist Pharmaceuticals, of Lexington, Mass., said in a release.
Ceftolozane is a novel member of the cephalosporin class of antibiotics, which appears to be more potent in vitro against Pseudomonas aeruginosa than available cephalosporins, the company said.
It’s being combined with tazobactam, a beta-lactamase inhibitor, in order to extend coverage to extended-spectrum beta-lactamase-producing bacteria.
The clinical trials included a total of 1,050 patients and compared the efficacy and safety of ceftolozane/tazobactam (1.5 g given intravenously every 8 hours) with intravenous levofloxacin (at 750 mg once a day).
The primary endpoint of the trial, for the purposes of the FDA, was noninferiority of ceftolozane/tazobactam among patients who reached both microbiological eradication and clinical cure 5 to 9 days after the last dose. The European standard was based on microbiological eradication.
For both standards, the drug combination met the 10% noninferiority margin, the company said. In fact, the 95% confidence interval around the treatment difference ranged from 2.3% to 14.6%, indicating statistical superiority, although the trials were not prospectively designed to demonstrate superiority.
Urinary Tract Infections (UTIs)
Urinary tract infections (UTIs) are a common type of infection caused by bacteria (most often E. coli) that travel up the urethra to the bladder. A bladder infection is called cystitis. If bacterial infection spreads to the kidneys and ureters, the condition is called pyelonephritis. Cystitis is considered a lower urinary tract infection. Pyelonephritis is an upper urinary tract infection and is much more serious.
Women are more susceptible to urinary tract infections than men, and their infections tend to recur. One reason is that the urethra (the tube that carries urine away from the bladder) is shorter in women than in men. Frequent sexual intercourse also increases a woman’s risk of developing UTIs. Contraceptive spermicides and diaphragm use are other risk factors. When women reach menopause, the decrease in estrogen thins the lining of the urinary tract, which increases susceptibility to bacterial infections.
Pregnancy does not increase the risk of getting a urinary tract infection but it can increase the risk of developing a serious infection that could potentially harm the mother and fetus. Pregnant women should report any symptoms of UTIs to their doctors, and should get screened for asymptomatic bacteriuria (presence of significant numbers of bacteria without symptoms).
About a third of patients in each arm of the studies reported treatment emergent adverse events – 34.7% for ceftolozane/tazobactam and 34.4% for levofloxacin. The most commonly reported adverse events for ceftolozane/tazobactam were headache (5.8%), constipation (3.9%), hypertension (3%), nausea (2.8%), and diarrhea (1.9%).
Steven Gilman, PhD, the company’s chief scientific officer, called the results a “significant milestone.”
Cubist is also conducting a phase III trial of ceftolozane/tazobactam, in combination with metronidazole (Flagyl), in patients with complicated intra-abdominal infections. The comparator drug in that trial is meropenem (Merrem) and the company said it expects results in late December.
Results from both the urinary tract infection and intra-abdominal infection trials are expected to form the basis for regulatory submissions.
By Michael Smith, North American Correspondent, MedPage Today