Resistance rifampin

Other examples include rifampin resistance due to mutations in the ipoB gene encoding the (3-subunit of RNA polymerase, or oxazolidinone resistance due to a G2576T mutation in the gene for the 23 S rRNA as central part of the 50S large ribosomal subunit. Macrolide resistance is based upon the alteration of nucleotide A2058 by a point mutation. 

Zhang W (2006) Microwave-Enhanced High-Speed Fluorous Synthesis. 266 145-166 Zhang X-E, Deng J-Y (2005) Detection of Mutations in Rifampin-Resistant Mycobacterium Tuberculosis by Short Oligonucleotide Ligation Assay on DNA Chips (SOLAC). 261 169-190... 

Troesch A et al. Mycobacterium species identification and rifampin resistance testing with high-density DNA probe arrays. J Clin Microbiol 1999 37 49-55. 

Patients with M. tuberculosis meningitis should be treated for a duration of 9 months or longer with multiple-drug therapy, and patients with rifampin-resistant strains should receive 18 to 24 months of therapy. 

To give the reader an idea of the practical effort of the immobilization strategies discussed, applications of these DNA chips are also included, e.g. with one chapter describing the immobilization step included in a short oligonucleotide ligation assay on DNA chip (SOLAC) to identify mutations in a gene of Mycobacterium tuberculosis in chnic isolates indicating rifampin resistance. 

Mycobacterium tuberculosis Add streptomycin or ethambutol as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. Streptomycin also is indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. 

In addition to M. tuberculosis, rifampin is active against Staphylococcus aureus, Neisseria meningitidis, Haemophilus influenzae, Chlamydiae, and certain viruses. Rifampin resistance results from a point mutation or deletion in rpoB, the gene for the p-subunit of RNA polymerase, thereby preventing the binding of RNA polymerase. 

Rifabutin is derived from rifamycin and is related to rifampin. It has significant activity against M tuberculosis, M avium-intracellulare, and M fortuitum (see below). Its activity is similar to that of rifampin, and cross-resistance with rifampin is virtually complete. Some rifampin-resistant strains may appear susceptible to rifabutin in vitro, but a clinical response is unlikely because the molecular basis of resistance, rpoB mutation, is the same. Rifabutin is both substrate and inducer of cytochrome P450 enzymes. Because it is a less potent inducer, rifabutin is indicated in place of rifampin for treatment of tuberculosis in HIV-infected patients who are receiving concurrent antiretroviral therapy with a protease inhibitor or nonnucleoside reverse transcriptase inhibitor (eg, efavirenz)—drugs that also are cytochrome P450 substrates. 

Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in lepromatous leprosy. Because of the probable risk of emergence of rifampin-resistant M leprae, the drug is given in combination with dapsone or another antileprosy drug. A single monthly dose of 600 mg may be beneficial in combination therapy. 

Xu M, Zhou YN, Goldstein BP et al (2005) Cross-resistance of Escherichia coli RNA polymerases conferring rifampin resistance to different antibiotics. J Bacteriol 187 2783-2792... 

In combination with an alkaline phosphatase reaction-linked assay, these two schemes have been used successfully for the identification of mutations in the rpoB gene of Mycobacterium tuberculosis from clinical isolates that show rifampin resistance (Rifr). The advantages and disadvantages of the new approach are discussed. 

Rifampin resistance Short oligonucleotide ligation on DNA chips (SOLAC) ... 

Detection of Mutations in Rifampin-Resistant Mycobacterium Tuberculosis... 

The 130 bp PCR products from 60 clinical isolates of M. tuberculosis, 55 known as rifampin-resistant and five known as rifampin-sensitive, were scanned for mutations by the SOLAC-GOS assay. Among the 55 rifampin-resistant isolates, 47 were found to have point mutations belonging to seven... 

Number of Strains Rifampin resistance a Mutations b CSOLA assay DNA sequencing... 

The RRDR of the rpoB gene was subsequently sequenced to analyze the mutations associated with rifampin resistance and to verify the detection results of the SOLAC-GOS assay. DNA sequencing analysis of the 55 Rifr isolates showed that 50 strains had point mutations, one strain had a double mutation, and one strain had a one-base deletion in the 81-bp RRDR of the rpoB gene. Three strains were found to have no mutation. A total of 52 mutations of 12 different types including 11 point mutations and one deletion were identified (Table 5). The most frequent mutations were found at codons 531, 526, and 516, with frequencies of 52.7,23.6, and 9.1%, respectively. Similar results have been reported by other investigators [36-38]. 

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