Isoniazid Mycobacterium tuberculosis

Mycobacterium tuberculosis Rifampicin + isoniazid + ethambutol + pyrazinamide ... 

Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycoUc acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drag with respect to these microorganisms. 

Pharmacology Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels, isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

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. 

Intended for use concomitantly with other antituberculosis agents in pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, when the primary agents (eg, isoniazid, rifampin) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli. Administration and Dosage... 

Mycobacterium tuberculosis Isoniazid + rifampin + ethambutol + pyrazinamide Streptomycin, moxifloxacin, amikacin, ethionamide, cycloserine, PAS, linezolid... 

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

A Banerjee, E Dubnau, A Quemard, V Balasubramanian, KS Um, T Wilson, D Collins, G de Lisle, WR Jacobs Jr. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263 227-230, 1994. 

K Mdluli, RA Slayden, Y Zhu, S Ramaswamy, X Pan, D Mead, DD Crane, JM Musser, CE Barry III. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid. Science 280 1607-1610, 1998. 

Cooksey RC, Holloway BP, Oldenburg MC, Listenbee S, Miller CW. Evaluation of the invader assay, a linear signal amplification method, for identification of mutations associated with resistance to rifampin and isoniazid in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2000 44(5) 1296-1301. 

Unissa AN, Sudha S, Selvakumar N, Hassan S (2011) Binding of activated isoniazid with acetyl-CoA carboxylase from Mycobacterium tuberculosis. Bioinformation 7 107-111... 

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... 

Based on the patient s history and lab information, he was started on a regimen of isoniazid, rifampin, pyrazinamide, and ethambutol while waiting for definitive cultures. (Six weeks later, definitive culture results demonstrated growth of Mycobacterium tuberculosis.) The patient returned to the clinic complaining of blurred vision and an inability to differentiate between green and red colors. 

Jacobs WR Jr, Blanchard JS. Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 1995 34 8235-8241. 41. 

Quemard A, Dessen A, Sugantino M, Jacobs MR Jr, Sacchettini JC, Blanchard JS. Binding of catalase-peroxidase-activated isoniazid to wild-type and mutant Mycobacterium tuberculosis enoyl-ACP reductases. J. Am. Chem. Soc. 1996 118 1561-1562. 

Rozwarski DA, Grant GA, Barton DHR, Jacobs WR Jr, Sacchettini 44. JC. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 1998 279 98-102. 

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. 

Treatment problems that can arise are mainly of two types adverse reactions (collateral, toxic, or hypersusceptibility reactions), and initial or acquired resistance of Mycobacterium tuberculosis, Mycobacterium bovis, or non-tuberculous mycobacteria to one or more of the antituberculosis drugs. The latter probably only occurs when the patient has not taken the full combination or the full doses of the drugs all the time. Combination formulations are thus particularly useful. Multidrug-resistant tuberculosis, defined as resistance against at least isoniazid and rifampicin, is the most clinically relevant form of resistance to treatment worldwide. 

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). 

Dickinson JM, Aber VR, Mitchison DA. Bactericidal activity of streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide alone and in combination against Mycobacterium tuberculosis. Am Rev Respir Dis 1977 116(4) 627-35. 

Reactivation of latent tuberculosis is a major concern with infliximab (SEDA-26, 402), and accounts for about one-third of infections in these patients. According to data from the manufacturers, 130 cases of active tuberculosis were notified up to October 2001. Many of the cases were disseminated or extrapulmonary tuberculosis, and several patients died. Several case reports have provided detailed information in at least seven other patients, including three who developed miliary tuberculosis and one who developed Mycobacterium tuberculosis enteritis (44-48). A detailed analysis of 70 cases of tuberculosis reported to the FDA has been published (49). Two-thirds of the cases were noted after three or fewer infusions and 57% of the patients had extrapulmonary disease. There were 64 cases from countries with a low incidence of tuberculosis. From these reports and the number of patients treated with infliximab, the estimated rate of tuberculosis in patients with rheumatoid arthritis treated with infliximab was four times higher than the background rate. Patients with evidence of active infection should not receive infliximab until the infection is under control all should be screened for tuberculosis before starting infliximab (50). From these and other data it has been estimated that the risk of tuberculosis in the first year of infliximab treatment is 0.035 in US citizens and 0.2% in non-US citizens. Further investigations, such as a chest X-ray and a Mantoux test, and prophylactic treatment with isoniazid, will show whether the incidence can be reduced in patients taking anti-TNF treatment (51). 

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