Dificid was originally called lipiarmycin—a whimsically phonetic spelling given to honor the leap-year day on which researchers in Italy discovered it nearly four decades ago. It is a naturally occurring 18-membered macrocyle that inhibits a key bacterial RNA polymerase, similar to members of the rifamycin family of macrocyclic antibiotics that also kill cells by interfering with gene transcription and, ultimately, blocking protein synthesis. The antibiotic was abandoned, however, when it was discovered that bacteria quickly develop resistance to it, according to David Rothstein, a Boston area consultant who specializes in antibiotic drug development. “But now people are finding uses for otherwise lousy antibiotics that don't get out of the gastrointestinal (GI) tract,” he says.
C. difficile–associated diarrhea (CDAD), the condition treated by Dificid, was recognized in the 1950s. It was then called antibiotic-associated diarrhea, and was blamed on other types of bacteria, until investigators learned two decades later that C. difficile is the principal culprit, according to David Aronoff of the University of Michigan, Ann Arbor. Typically, CDAD arises after antibiotic treatments, which tend to disrupt the normal gut flora allowing the overgrowth of toxigenic strains of C. difficile and the production of toxins A and B. Reactions to these toxins can produce lesions and severe damage to the epithelial lining of the colon, resulting in diarrhea that can be persistent and, in some cases lethal, particularly among the elderly or other vulnerable patient groups. Although stringent hygiene practices help to prevent CDAD from moving from one patient to others, the prevalence of CDAD appears to be rising in hospital and other institutional settings, and could affect 3 million individuals in the US per year, costing as much as $3 billion in total due to extended hospital stays and treatments.
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