Mycobacterial infections tuberculosis

The advent of multidrug resistant strains of Mycobacterium tuberculosis (MDR-TB) has led to increased fears of untreatable infections by serious pathogens. Rifampicin, streptomycin and, occasionally, the quinolones are drugs used in the treatment of mycobacterial infections and resistance to those agents is as described previously. There... 

Tuberculosis is on the increase in developed countries such as the USA and UK furthermore, MAI may be associated with AIDS sufferers. Hospital-acquired opportunistic mycobacteria may cause disseminated infection and also lung infections, endocarditis and pericarditis. Transmission of mycobacterial infection by endoscopy is rare, despite a marked increase in the use of flexible fibreoptic endoscopes, but bronchoscopy is probably the greatest hazard for the transmission ofM tuberculosis and other mycobacteria. Thus, biocides used for bronchoscope disinfection must be ehosen carefully to ensure that such transmission does not occur. 

Heifets LB. Drug susceptibility tests in the management of chemotherapy of tuberculosis. In Heifets LB, ed. Drug Susceptibility in the Chemotherapy of Mycobacterial Infections. Boca Raton, FL CRC Press 1991 89-122. 

Immune reconstitution syndrome A syndrome characterized by fever and worsening of clinical symptoms of opportunistic infections or new symptoms occurring within weeks after starting antiretroviral therapy. This has been described for mycobacterial infections (Mycobacterium avium complex and Mycobacterium tuberculosis), Pneumocystis proved pneumonia, toxoplasmosis,... 

Streptomycin is mainly used as a second-line agent for treatment of tuberculosis. The dosage is 0.5-1 g/d (7.5-15 mg/kg/d for children), which is given intramuscularly or intravenously. It should be used only in combination with other agents to prevent emergence of resistance. See Chapter 47 for additional information regarding the use of streptomycin in mycobacterial infections. 

Ciprofloxacin and levofloxacin are no longer recommended for the treatment of gonococcal infection in the USA as resistance is now common. However, both drugs are effective in treating chlamydial urethritis or cervicitis. Ciprofloxacin, levofloxacin, or moxifloxacin is occasionally used for treatment of tuberculosis and atypical mycobacterial infections. These agents may be suitable for eradication of meningococci from carriers or for prophylaxis of infection in neutropenic patients. 

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. 

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. 

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... 

Note The treatment of mycobacterial infections has become an even more important and challenging problem because of the emergence of multiple-drug-resistant organisms and because of the acquired immunodeficiency syndrome (AIDS) pandemic, which has been associated with a marked increase in tuberculosis and infection caused by the M. avium complex. Because the microorganisms grow slowly and the diseases often are chronic, patient compliance, drug toxicity, and the development of microbial resistance present special therapeutic problems. 

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. 

Rifabutin may be used in the prophylaxis of M. avium complex infections in immunocompromised patients and in the treatment, with other drugs, of pulmonary tuberculosis and non-tuberculous mycobacterial infections. 

Mycobacterium tuberculosis LX are negative regulators of the THl response to mycobacterial infection Transgenic animals deficient in producing lipoxins have elevated levels of interleukin-12, interferon-y and nitric oxide synthase 2 mRNA, as weU as decreased bacterial burden in lung tissue Bafica et al. 2005... 

Dendritic cells (DC) and macrophages exposed to live microfilariae in vitro show rednced matnration after M. tuberculosis infection, indicating a compromised activation of the immune system by mycobacteria upon co-infection with helminths (Talaat et al. 2006), thereby possibly reducing the susceptibility of DC for infection by M. tuberculosis. Thus, in vitro studies indicate that helminths can suppress the immune response to mycobacterial infections. However, the in vivo relevance of in vitro findings has to be more intensively examined. 

Granulomatous forms of meningitis and cerebritis are seen in tuberculosis and other mycobacterial infections fungal, parasitic, or spirochetal infections idiopathic conditions, such as sarcoidosis, systemic lupus erythematosus, Wegener s and lymphomatoid granulomatoses and histiocytosis X. 

Rifamycin B, produced by Amycolatopsis mediterranei, is one of the most notable members of the ansamycin family [36, 37, 64, 65] (Fig. 14). It has been used clinically in a synthetically modified form called rifampicin and it is still one of the first-line therapies effective in the treatment of tuberculosis and other mycobacterial infections. The starter unit for rifamycin polyketide assembly is part of the chromophore and is derived from 3-amino-5-hydroxybenzoic acid. Five polyketide synthases are involved in the formation of rifamycin chromophore and the first polyketide synthase contains at the N terminus the loading domain for 3-amino-5-hydroxybenzoic acid, which consists of an acyl-CoA ligase linked to ACP, and module 1-3. The rifamycin polyketide synthase lacks a TE domain at the C terminus. The release of polyketide chain from polyketide synthase and the formation of amide to generate the macrocyclic lactam will be catalyzed by RifF, which is very similar to arylamine A-acetyltransferase. 

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