Tuberculosis pyrazinamide

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

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. 

Ms. Burns has received a diagnosis of tuberculosis. She is concerned because her primary health care provider has informed her that the treatment regimen consists of three drugs, isoniazid, rifampin, and pyrazinamide, taken for the next 2 months, followed by a 4-month treatment regimen with two of the drugs. 

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

Centers for Disease Control and Prevention. Update Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in the American Thoracic Society/CDC recommendations. Morb Mortal Wkly Rep MMWR 2001 50(34) 733-735. 

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. 

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)... 

M. A. Miller, L. Thibert, F. Desjardins, H. Siddiqi, A. Dascal, Testing the Susceptibility of Mycobacterium tuberculosis to Pyrazinamide Comparision of Bactec Method with Pyrazinamidase Assay , J. Clin. Microbiol. 1995, 33, 2468-2470. 

Tuberculosis (TB) - The standard regimen for the treatment of drug-susceptible TB has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of... 

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. 

Oral - Oral treatment is for all forms of tuberculosis. A 3-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of short-course therapy that is usually continued for 2 months. 

The 4-month regimen According to the MMWR, rifampin given daily for 3 months has resulted in better protection than placebo in treatment of LTBI in non-HIV patients with silicosis in a randomized prospective trial. However, because the patients receiving rifampin had a high rate of active tuberculosis (4%), experts have concluded that a 4-month regimen would be more prudent when using rifampin alone. This option may be useful for patients who cannot tolerate isoniazid or pyrazinamide. 

The current CDC recommendation for drug-susceptible initial treatment of active tuberculosis disease is a 6-month regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Treatment failure After treatment failure with other primary drugs in any form of active tuberculosis. 

Pharmacology Pyrazinamide, the pyrazine analog of nicotinamide, may be bacteriostatic or bactericidal against Mycobacterium tuberculosis depending on the concentration of the drug attained at the site of infection. The mechanism of action is unknown. 

Primary resistance of M. tuberculosis Primary resistance of M. tuberculosis to pyrazinamide is uncommon. In cases with known or suspected drug resistance, perform in vitro susceptibility tests with recent cultures of M. tuberculosis against pyrazinamide and the usual primary drugs. 

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. 

Tuberculosis The standard regimen for the treatment of drug-susceptible tuberculosis has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of INH and rifampin (patients with concomitant infection with tuberculosis and HIV may require treatment for a longer period). When streptomycin is added to this regimen because of suspected or proven drug resistance, the recommended dosing for streptomycin is as follows ... 

Pyrazinamide is a nicotinamide derivative. It has mycobactericidal activity with a high specificity for Mycobacterium tuberculosis. Its mechanism of action is not well understood. 

Treatment of latent tuberculosis infection (LTBI) with isoniazid (INH) is very effective in preventing persons infected with M. tuberculosis from developing tuberculosis, regardless of HIV-1 serostatus. Several recent studies have shown that rifampicin and pyrazinamide taken for 2 months is as effective as 6-12 months of INH for the prevention of active TBC in HIV-1 seropositive persons although more hepatotoxicity is seen. 

Pyrazinamide is an essential component of the multidrug short-term therapy of tuberculosis. In combination with isoniazid and rifampin, it is active against the intracellular organisms that may cause relapse. 

Streptomycin is indicated as a fourth drug in combination with isoniazid, rifampin, and pyrazinamide in patients at high risk for drug resistance. It is also used in the treatment of streptomycin-susceptible MDR tuberculosis. 

Rifabutin appears as effective as rifampin in the treatment of drug-susceptible tuberculosis and is used in the treatment of latent tuberculosis infection either alone or in combination with pyrazinamide. Clinical use of rifabutin has increased in recent years, especially in the treatment of HIV infection. It is a less potent inducer of cytochrome 450 enzymes pathways than rifampin and results in less drug interaction with the protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Rifabutin is therefore commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. Another important use of rifabutin in the HIV-infected population is prevention and treatment of disseminated MAC. 

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

C. Pyrazinamide is known to cause hyperuricemia and precipitate gouty arthritis. Pyrazinamide-induced gouty arthritis does not respond to uricosuric therapy with probenecid but may respond to acetylsalicylic acid. Cycloserine (A) can cause headaches, confusion, tremors, and seizures, possibly secondary to low levels of magnesium in the cerebrospinal fluid cycloserine should be avoided in patients with epilepsy and mental depression. It is not associated with hyperuricemia. Thiacetazone (B) is an antibiotic that is rarely used in tuberculosis. The most common adverse reactions are general rashes and GI intolerance. Its use is not associated with hy-... 

Update fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection. MMWR 2001 50 733-735. 

Rifabutin is effective in prevention and treatment of disseminated atypical mycobacterial infection in AIDS patients with CD4 counts below 50/pL. It is also effective for preventive therapy of tuberculosis, either alone in a 3-4 month regimen or with pyrazinamide in a 2-month regimen. 

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

Tuberculosis Persons with positive tuberculin skin tests and one or more of the following (a) HIV infection, (b) close contacts with newly diagnosed disease, (c) recent skin test conversion, (d) medical conditions that increase the risk of developing tuberculosis, (e) age < 35 Isoniazid, rifampin, or pyrazinamide Excellent... 

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. 

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