Mutation and resistance

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Dutartre H, Bussetta C, Boretto J, Canard B (2006) General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2 -modified nucleotide analogues. Antimicrob Agents Chemother 50 4161 169 Elferink RO, Groen AK (2002) Genetic defects in hepatobiliary transport. Biochim Biophys Acta... 

Melby TE, Despirito M, Demasi RA, HeUek G, Thommes JA, Greenberg ML, Graham N (2007b) Association between specific enfuvirtide resistance mutations and CD4 cell response during enfuvirtide-based therapy. Aids 21 2537-2539... 

Taken together, the genetic barrier cannot be simply defined by the sum of resistance mutations, but also the genetic background of the virus, the variation in the viral population, interaction of mutations, and their impact on viral replication play a role. 

Lu L, Dekhtyar T, Masse S, PithawaUa R, Krishnan P, He W, Ng T, Koev G, Stewart K, Larson D, Bosse T, Wagner R, PUot-Matias T, Mo H, MoUa A (2007) Identification and characterization of mutations conferring resistance to an HCV RNA-dependent RNA polymerase inhibitor in vitro. Antiviral Res 76 93-97... 

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