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FDA Grants ‘Fast Track’ Designations for Antibiotic Candidates

Drugs target gram-negative infections and <i>C. difficile</i> diarrhea (Feb. 28)

The FDA has designated the late-stage antibiotic candidate ceftolozane/tazobactam (CXA-201, Cubist Pharmaceuticals) as a Qualified Infectious Disease Product (QIDP) for the indications of hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP) and complicated urinary tract infection (cUTI).

In addition, the FDA has granted “fast track” designations for the antibiotic candidates ceftolozane/tazobactam and surotomycin (CB-315, Cubist) in their previously granted QIDP indications — complicated intra-abdominal infection (cIAI) and Clostridium difficile-associated diarrhea (CDAD), respectively.

Ceftolozane/tazobactam is currently being studied in pivotal phase III trials as a potential first-line intravenous treatment for cIAI and cUTI caused by gram-negative pathogens, including those caused by multidrug-resistant Pseudomonas aeruginosa. A phase III program for ceftolozane/tazobactam in the treatment of VABP is expected to begin by mid-year. Surotomycin, a bactericidal lipopeptide, is currently in phase III development as a potential treatment for patients with severe and potentially life-threatening CDAD.

The diseases caused by gram-negative bacteria include UTIs, intra-abdominal infections, pneumonia, peritonitis, septicemia, neonatal meningitis, and burn and wound infections. In the U.S. in 2003, gram-negative bacteria were associated with many of the most frequent types of hospital-acquired infections, including 71% of UTIs, 65% of pneumonia episodes, 34% of surgical-site infections, and 24% of bloodstream infections. Important gram-negative bacteria include Pseudomonas, Escherichia coli, Klebsiella, and Acinetobacter.

CDAD is a disease caused by an overgrowth of, and toxin production by, C. difficile, a gram-positive bacterium naturally found in the lower gastrointestinal tract. This overgrowth is caused by the use of antibiotics for the treatment of common community- and hospital-acquired infections. Many antibiotics cure the underlying infection but, as a consequence, disrupt the natural balance of intestinal bacteria, which allows C. difficile to overgrow. The overgrown C. difficile bacteria produce enterotoxin and cytotoxin — two proteins that can lead to potentially life-threatening severe diarrhea and sepsis.

According to an article in the October 2008 issue of the New England Journal of Medicine, during the mid and late 1990s, the reported incidence of C. difficile infections in acute-care hospitals in the U.S. remained stable at 30 to 40 cases per 100,000. However, in 2001 this number rose to almost 50, with subsequent increases to the point that the number of cases that were reported in 2005 (84 per 100,000) was nearly three times the 1996 rate (31 per 100,000).

Source: Cubist Pharmaceuticals; February 28, 2013.

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