Mycobacterial infections treatment

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... 

Heginbotham, M. L. Magee, J. T. Pyrolysis mass spectrometry A predictor of clinical response to treatment in pulmonary oppurtunist mycobacterial infection preliminary work with M. malmoense. Zbl. Bakt. 1996, 285, 291-298. 

Mycobacterial infections - Recommended as the primary agent for the treatment of disseminated MAC. Use in combination with other antimycobacterial drugs that have shown in vitro activity against MAC. 

The aminoglycoside (see Section II.c) streptomycin was the first antimycobacterial antibiotic. It has activity against extracellular mycobacteria with a high growth rate. The macrolide antibiotics azithromycin and clarithromycin (see Section Il.d.l) were approved for the treatment of disseminated mycobacterial infections due to Mycobacterium avium complex. 

Unlabeled Uses Treatment of atypical mycobacterial infections... 

Uniabeled Uses Treatment of atypical mycobacterial infections, gonorrhea, malaria, rheumatoid arthritis prevention of Lyme disease prevention or treatment of traveler s diarrhea. 

Unlabeled Uses Treatment of atypical mycobacterial infections such as Mycobacterium avium complex (MAC)... 

Unlabeled Uses Prophylaxis of Haemophilus influenzae type b infection treatment of atypical mycobacterial infection and serious infections caused by Staphybcoccus spe-... 

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. 

A combination of trimethoprim-sulfamethoxazole is effective treatment for a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. It is active against most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, and against respiratory tract pathogens such as the pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae (but not Mycoplasma pneumoniae). However, the increasing prevalence of strains of E coli (up to 30% or more) and pneumococci that are resistant to trimethoprim-sulfamethoxazole must be considered before using this combination for empirical therapy of upper urinary tract infections or pneumonia. 

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. 

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. 

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 (t 36 h) has similar activity and adverse reactions, and is used for prophylaxis of Mycobacterium avium infection in patients with AIDS, and for treatment of tuberculous and nontuberculous mycobacterial infection in combination with other drugs. 

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. 

Risk of opportunistic infections associated with decreased T-cell function for several months after treatment (PCP, mycobacterial infections) prophylactic antibiotics for PCP and HSV should be considered, particularly when fludarabine is used in combination with corticosteroids Rapid cell kill tumor lysis syndrome precautions needed reduce dose with impaired renal function... 

Clarithromycin is an H. pylori agent/macrolide, which inhibits microbial protein synthesis. Clarithromycin is indicated in the treatment of infections of the respiratory tract, skin and skin structure treatment of disseminated atypical mycobacterial infections caused by susceptible strains of specific microorganisms and prevention of disseminated Mycobacterium avium complex disease in patients with advanced HIV infection. Clarithromycin in combination with omeprazole is indicated in the treatment of patients with an active duodenal ulcer associated with H. pylori infection. In children it is used in acute otitis media. Macrolides are erythromycin, clarithromycin, and azithromycin. 

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. 

Tartaglione, T. (1997). Treatment of nontuberculous mycobacterial infections Role of clarithromycin and azithromycin. Clin. Then 19, 626-638 discussion 603. 

The use of these drugs in the treatment and prevention of mycobacterial infections is described in... 

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