ansamycin

Ansamycin is a class of antibiotics characterized by an ansa bridge that connects a macrocyclic ring to a naphthoquinone nucleus, forming a distinctive ansamycin structure. The best-known members are the rifamycins, a group produced by actinomycete bacteria.

Most rifamycins are produced by Amycolatopsis mediterranei (formerly Streptomyces mediterranei). The core scaffold is rifamycin B; derivatives include rifampicin (rifampin), rifabutin, rifapentine, and rifaximin, among others. Substitutions on this scaffold alter spectrum, potency, and pharmacokinetics.

Mechanism of action: Rifamycins bind to the beta-subunit of bacterial DNA-dependent RNA polymerase (RpoB), inhibiting RNA synthesis and producing bactericidal activity, particularly against Mycobacteria and intracellular pathogens. Activity varies by species, and some Gram-negative bacteria are less susceptible.

Clinical use and pharmacology: These drugs are most important as components of combination regimens for tuberculosis and other mycobacterial infections. They are also used for selected prophylactic indications. Rifamycins are potent enzyme inducers, leading to numerous drug interactions; common adverse effects include hepatotoxicity, hypersensitivity, and flu-like symptoms. A characteristic feature is the reddish-orange discoloration of bodily fluids.

Resistance: Resistance develops rapidly through mutations in rpoB, leading to cross-resistance among rifamycins. Because of this, monotherapy is avoided and rifamycins are used in combination with other agents.