Ethambutol tuberculosis

Introdnced in 1961 for the treatment of tuberculosis, ethambutol supplanted para-aminosalicylic acid fiar the initial treatment and retreatment of tuberculosis. 

The initial phase must contain three or more of the following drugp isoniazid, rifampin, and pyrazin-amide, along with either ethambutol or streptomycin. The CDC recommends treatment to begin as soon as possible after the diagnosis of tuberculosis. The treatment recommendation regimen is for the administration of rifampin, isoniazid, and pyrazinamide for a minimum of 2 months (8 weeks), followed by rifampin and isoniazid for 4 months (16 weeks) in areas with a low incidence of tuberculosis. In areas of high incidence of tuberculosis, the CDC recommends the addition of streptomycin or ethambutol for the first 2 months. 

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

The Centers for Disease Control and Prevention recommends a regimen of four drugs for empiric treatment of M. tuberculosis. This regimen should consist of isoniazid, rifampin, pyrazinamide, and ethambutol, 15 to 20 mg/kg/day (maximum 1.6 g/day) for the first 2 months generally followed by isoniazid plus rifampin for the duration of therapy. 

HIV - The initial phase of a 6-month tuberculosis regimen consists of isoniazid, rifabutin, pyrazinamide, and ethambutol for patients receiving therapy with protease inhibitors or nonnucleoside reverse transcriptase inhibitors. These drugs are administered a) daily for at least the first 2 weeks, followed by twice weekly dosing for 6 weeks or b) daily for 8 weeks to complete the 2-month induction phase. The second phase of treatment consists of rifabutin and isoniazid administered twice weekly or daily for 4 months. 

Do not use tuberculosis regimens consisting of isoniazid, ethambutol, and pyrazinamide (ie, 3-drug regimens that do not contain a rifamycin, an aminoglycoside [eg, streptomycin, amikacin, kanamycin], or capreomycin) for the treatment of patients with HIV-related tuberculosis. The minimum duration of therapy is 18 months (or 12 months after documented culture conversion) if these regimens are used for the treatment of 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. 

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis. 

Use of PAS has diminished over the years following the introduction of more effective drugs, such as rifampin and ethambutol. At present, therapy with PAS is limited to the treatment of MDR tuberculosis. Problems with primary resistance, poor compliance due to GI intolerance, and lupuslike reactions have further discouraged its use. 

Quinolones are important recent additions to the therapeutic agents used against M. tuberculosis, especially in MDR strains. Clinical trials of ofloxacin in combination with isoniazid and rifampin have indicated activity comparable to that of ethambutol. In addition, quinolones, particularly ciprofloxacin, are used as part of a combined regimen in HIV-infected patients. 

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... 

Initial therapy in tuberculosis should include 4 drugs isonlazid, rifampin, pyrazina-mide, and ethambutol, until drug susceptibility results available... 

Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 mcg/mL. Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene. 

M kansasii Resembles tuberculosis Ciprofloxacin, clarithromycin, ethambutol, isoniazid, rifampin, trimethoprim-sulfamethoxazole... 

Ethambutol Inhibits mycobacterial arabinosyl transferases, which are involved in the polymerization reaction of arabinoglycan an essential component of the mycobacterial cell wall Bacteriostatic activity against susceptible mycobacteria Given as four-drug initial combination therapy for tuberculosis until drug sensitivities are known also used for atypical mycobacterial infections Oral t mixed clearance (half-life 4 h) dose must be reduced in renal failure Toxicity Retrobulbar neuritis... 

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

Streptomycin (Boxes 20-B, 20-H) was introduced into clinical use against tuberculosis in about 1943. However, resistant mutants always survived until newer drugs were developed. Isonicotinylhydrazide (isoniazid) is especially effective in combinations with suitable antibiotics and other drugs.8 The four-drug combination isoniazid, rifampicin (Box 28-A), pyrazinamide, and ethambutol is often used. Nevertheless, bacteria resistant to all of these have developed. 

The mechanism of ethambutol (Myambutol) is not fully understood. This drug apparently suppresses RNA synthesis in susceptible bacteria, but it is not known how this occurs. Ethambutol is primarily effective against M. tuberculosis infections and is a secondary agent in the treatment of tuberculosis.61 Adverse effects associated with this drug include joint pain, nausea, skin rash and itching, and CNS abnormalities (dizziness, confusion, hallucinations). 

During the initial phase, isoniazid is always used in combination with one other drug — rifampin, streptomycin, or ethambutol. In advanced or cavitary pulmonary tuberculosis, often three drugs are used — isoniazid, rifampin, and streptomycin or ethambutol. The pharmacological properties of the most often used drugs are summarized in Table 39.1. 

Not all mycobacterial infections are caused by M. tuberculosis or M. leprae. These atypical mycobacteria require treatment with secondary medications as well as other chemotherapeutic agents. For example, M. marinum causes skin granulomas, and effective drugs in the treatment of infection are rifampin or minocycline. Mycobacterium fortuitum causes skin ulcers and the medications recommended for treatment are ethambutol, cycloserine, and rifampin in combination with amikacin. 

Because of the dangerous adverse reactions (including the risk of death), individuals should not take methylphenidate if they have taken a class of drugs known as monamine oxidase (MAO) inhibitors within 14 days. Most MAO inhibitors are antidepressants, but some anti-tuberculosis drugs such as Ethambutol also have MAO effects. Since drug users are prone to many infectious diseases, it is not unheard of for drug abusers to come down with tuberculosis (TB). 

Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the five first-line agents for treatment of tuberculosis (Table 47-1). Isoniazid and rifampin are the two most active drugs. An isoniazid-rifampin combination administered for 9 months will cure 95-98% of cases of tuberculosis caused by susceptible strains. The addition of pyrazinamide to an isoniazid-rifampin combination for the first 2 months allows the total duration of therapy to be reduced to 6 months without loss of efficacy (Table 47-2). In practice, therapy is initiated with a four-drug regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin until susceptibility of the clinical isolate has been determined. Neither ethambutol nor streptomycin adds substantially to the overall activity of the regimen (ie, the duration of treatment cannot be further reduced if either drug is used), but they do provide additional coverage should the isolate prove to be resistant to isoniazid, rifampin, or both. Unfortunately, such resistance occurs in up to 10% of cases in the United States. Most patients with tuberculosis can be treated entirely as outpatients, with... 

Rifampin, usually 600 mg/d (10 mg/kg/d) orally, is administered together with isoniazid, ethambutol, or another antituberculous drug in order to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin is given twice weekly. Rifampin 600 mg daily or twice weekly for 6 months also is effective in some atypical mycobacterial infections and in leprosy when used together with a sulfone. Rifampin is an alternative to isoniazid prophylaxis for patients who are unable to take isoniazid or who have had close contact with a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain. 

Susceptible strains of M tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 pgJmL. Ethambutol is an inhibitor of mycobacterial arabinosyl transferases, which are encoded... 

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