Isoniazid resistance

Rifampin Daily for 4 months For persons who are contacts of patients with isoniazid-resistant rifampin susceptible TB. In HIV-infected patients, protease inhibitors or NNRTIs generally should not be administered concurrently with rifampin rifabutin can be used as an alternative for patients treated with indinavir, nelfinavir, amprenivir, ritonavir, orefavirenz, and possibly with nevirapine or soft-gel saquinavir5 B (II) B (III)... 

Direct InhA inhibitors have also been sought to avoid isoniazid resistance mediated by catalase-peroxidase mutation. Lipophilic analogs of triclosan such as 36 show a nanomolar K on the enzyme with an MIC of 1-2 pg/mL on isoniazid-resistant strains [56]. Structure-based optimization of two separate HTS leads afforded 37 and 38, both submicromolar inhibitors of InhA but devoid of any significant antibacterial activity [57,58],... 

Same as isoniazid sensitive high probability of exposure to isoniazid-resistant tuberculosis... 

Rifampin Daily for 4 months For persons who are contacts of patients with isoniazid-resistant, rifampin-susceptible tuberculosis who cannot tolerate pyrazinamide B (II) B OH)... 

The most common mechanism of isoniazid resistance is the mycobacteria s formation of mutations in catalase-peroxidase KatG, the enzyme that is responsible for activation of isoniazid. Another resistance mechanism is through a missense mutation related to the inhA gene involved in mycolic acid biosynthesis. 

Rifampin and pyrazinamide daily for 2 months is appropriate for isoniazid-resistant tuberculosis. 

The most commonly used regimen for drug-susceptible tuberculosis consists of isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily or two to three times a week for 4 months. If isoniazid resistance is suspected, ethambutol or streptomycin should be added to the regimen until the susceptibility of the mycobacterium is determined. This... 

Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin are given twice weekly. Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tuberculosis only, who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain. 

Mycobacterium tuberculosis Tuberculosis Isoniazid plus pyridoxine rifampin (if isoniazid resistant)... 

Wahab HA, Choong YS, Ibrahim P et al (2009) Elucidating isoniazid resistance using molecular modeling. J Chem Inf Model 49 97-107... 

Ghiladi RA, Medzihradszky KF, Rusnak FM et al (2005) Correlation between isoniazid resistance and superoxide reactivity in Mycobacterium tuberculosis KatG. J Am Chem Soc 127 13428-13442... 

Musser JM, Kapur V, Wilhams DL, Kreiswirth BN, van Soolingen D, van Embden JD. Characterization of the catalase-peroxidase gene (katG) and inhA locus in isoniazid-resistant and -susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing restricted array of mutatins associated with drag re- 45. sistance. J. Infect. Dis. 1996 173 196-202. 

As a rule, a regimen of two, three, or four of the five first-line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) is used in tuberculosis (1). The 6-month short-course regimen consists of isoniazid, rifampicin, and pyrazinamide for 2 months, followed by isoniazid and rifampicin for 4 months (1). It may be advisable to include ethambutol in the initial phase when isoniazid resistance is suspected or if the prevalence of primary resistance to isoniazid is over 4% in new cases. A 9-month regimen consisting of isoniazid and rifampicin is also highly successful (1). Treatment should always include at least two drugs to which the mycobacteria are susceptible. 

Ethambutol is tuberculostatic and acts against Mycobacterium tuberculosis and Mycobacterium kansasii as well as some strains of Mycobacterium avium complex. It has no effect on other bacteria. The sensitivities of non-tuberculous mycobacteria are variable. Ethambutol suppresses the growth of most isoniazid-resistant and streptomycin-resistant tubercle bacilli (1). 

Marin M, Garcia de Viedma D, Ruiz-Serrano MJ, Bouza E. Rapid direct detection of multiple rifampin and isoniazid resistance mutations in Mycobacterium tuberculosis in respiratory samples by real-time PCR. Antimicrob Agents Chemother 2004 48 4293M300. 

Isoniazid-resistant Same as isoniazid-sensitive high probability of exposure to isoniazid-resistant tuberculosis Rifampin 600 mg orally once daily plus pyrazinamide 200 mg/kg orally once daily for 2 mo... 

Isoniazid resistance most commonly results from mutations in catalase-peroxidase that decrease its activity, preventing conversion of the prodrug isoniazid to its active metabolite. Mutations in genes involved in mycolic acid biosynthesis also cause resistance. 

Middlebrook, G., 1954. Isoniazid-resistance and catalase activity of tubercle bacilli a preliminary report. Am. Rev. Tuberc. 69 (3), 471—472. 

Zhang, Y., Heym, B., Allen, B., Young, D., Cole, S., 1992. The catalase-peroxidase gene and isoniazid resistance of mycobacterium tuberculosis. Nature 358 (6387), 591—593. Available from http //dx.doi.org/10.1038/358591a0. 

Peptide Antibiotics. Capreomycin has been evaluated in combination vith PAS, ° with PAS and isoniazid, 1 O and with ethambutol,1° in the treatment and re-treatment of chronic pulmonary tuberculosis as a result the use of capreomycin in multiple drug combinations has been advocated for the treatment of infections due to isoniazid resistant tubercle bacilli. 1... 

Ahmad S, Mokaddas E. Contribution of AGC to ACC and other mutations at Codon 315 of the kat G gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East. Int J Antimicrob Agents 2004 23(5) 473-9. 

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