Tuberculosis rifampin

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. 

Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapul-monary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis. 

Mycobacterium tuberculosis Rifampin + isoniazid Gram-negative aerobic bacteria Streptomycin... 

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... 

The discovery of rifampicin in 1967 is considered one of the greatest achievements in the history of chemotherapy against tuberculosis. Rifampin was developed in the Lepetit Research Laboratories (Italy) as part of an extensive program of chemical modification of the rifamycins, the natural metabolites of Nocardia mediterranei. All of the studies leading to highly active derivatives were performed on a molecule (rifamycin B) that was itself practically inactive. Systematic structural modifications of most of the functional groups of the rifamycin molecule were... 

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

Most aiititubercular drag s are bacteriostatic (slow or retard the growth of bacteria) against the M. tuberculosis bacillus. These dm usually act to inhibit bacterial cell wall synthesis, which slows the multiplication rate of the bacteria. Only isoniazid is bactericidal, with rifampin and streptomycin having some bactericidal 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. 

Isoniazid and rifampin are the two most important tuberculosis drugs organisms resistant to both these drugs [multidrug-resistant tuberculosis (MDR-TB)] are much more difficult to treat. 

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. 

Multidrug resistant tuberculosis (TB) The presence of at least 1% of Mycobacterium strains in a bacterial population or culture that are resistant to at least isoniazid and rifampin. 

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... 

Three studies have addressed the possibility of inducing cross-resistance to Mycobacterium tuberculosis during the use of rifaximin. In an experimental guinea pig model of M. tuberculosis, rifaximin was administered in an effort to induce resistance among M. tuberculosis strains of human origin. Not only did no resistance develop, crossresistance to rifampin also did not occur [17, 18]. In another approach, M. tuberculosis strains were subjected to subinhibitory concentrations of rifaximin. No induction of resistance or cross-resistance to rifampin occurred... 

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. 

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. 

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 long-term (more than several weeks) use of levofloxacin in children and adolescents has not been approved because of concerns about effects on bone and cartilage growth. However, most experts agree that the drug should be considered for children with tuberculosis caused by organisms resistant to both isoniazid and rifampin. The optimal dose is not known. 

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. 

Rifampin inhibits the bacterial enzyme that catalyzes DNA template-directed RNA transcription, i.e DNA-de-pendent RNA polymerase. Rifampin acts bactericidally against mycobacteria (M. tuberculosis, M. leprae), as well as many gram-positive and gram-negative bacteria It is well absorbed after oral ingestion. Because resistance may develop with frequent usage, it is restricted to the treatment of tuberculosis and leprosy (p. 280). 

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... 

Because the MMWRs most recent recommendations for the use of antiretroviral therapy strongly advise against interruptions of therapy, and because alternative tuberculosis treatments that do not contain rifampin are available, previous antituberculosis therapy options that involved stopping protease inhibitor therapy to allow the use of rifampin are no longer recommended. 

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. 

Pharmacology Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase, but does not inhibit the mammalian enzyme. Cross-resistance has only been shown with other rifamycins. Rifampin at therapeutic levels has demonstrated bactericidal activity against intracellular and extracellular Mycobacterium tuberculosis organisms. Pharmacokinetics ... 

Metabolism Rifampin is metabolized in the liver by deacetylation the metabolite is still active against Mycobacterium tuberculosis. About 40% is excreted in bile and undergoes enterohepatic circulation however, the deacetylated metabolite is poorly absorbed. The half-life is approximately 3 hours after a 600 mg oral dose, up to 5.1 after a 900 mg oral dose. With repeated administration, the half-life decreases and averages approximately 2 to 3 hours. 

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. 

Tuberculosis Treatment of tuberculosis in combination with other active agents. It is most commonly used in patients with multi-drug resistant tuberculosis (MDR-TB) or in situations when therapy with isoniazid and rifampin is not possible because of a combination of resistance and intolerance. 

Recommended for any form of active tuberculosis when treatment with first-line drugs (isoniazid, rifampin) has failed. Use only with other effective antituberculosis... 

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 ... 

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... 

Other major untoward reactions are the result of rifampin s ability to induce hepatic cytochrome P-450 enzymes, leading to an increased metabolism of many drugs this action has especially complicated the treatment of tuberculosis in HIV-infected patients whose regimen includes protease inhibitors and nonnucleoside reverse transcriptase. Since rifabutin has relatively little of these effects, it is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. 

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. 

---