Azithromycin: Indication, dosage and administration and side effects

Antimycobacterial Agents

Antimycobacterial Agents

Because many antimicrobial agents have poor activity against slowly dividing bacteria, mycobacteria are prone to develop resistance to antibiotics. As a result, treatment of infections caused by mycobacteria requires multiple antimicrobial agents for extended periods. Different species of mycobacteria cause different diseases, each of which requires its own unique therapeutic regimen.

Tuberculosis is caused by Mycobacterium tuberculosis. Mycobacterium avium complex is a group of mycobacteria that frequently cause disease in immunocompromised hosts, particularly those infected with HIV. The disfi guring disease leprosy is caused by Mycobacterium leprae. A long list of other mycobacteria, often referred to as atypical mycobacteria, also cause various diseases in humans. Agents commonly used to treat mycobacterial infections include isoniazid

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, rifampin, rifabutin, pyrazinamide, ethambutol, clarithromycin, and azithromycin. Other agents occasionally used in the treatment of mycobacterial infections include amikacin, streptomycin, cycloserine, ethionamide, capreomycin p-aminosalicylic acid, clofazimine, dapsone, and the quinolones.

ISONIAZID

Isoniazid has little activity against most bacteria but is capable of killing both intracellular and extracellular M. tuberculosis. It is thought to inhibit an enzyme essential for the synthesis of mycolic acid, an important constituent of the M. tuberculosis cell envelope. This may explain the specifi city of isoniazid for mycobacteria because other bacteria do not make mycolic acid. Resistance occurs with mutations in the gene that encodes catalase-peroxidase, which is required to convert isoniazid to its active form.

Likewise, mutations in the gene encoding the target enzyme essential for mycolic acid synthesis also result in resistance. Isoniazid is associated with rash, fever, hepatotoxicity, and peripheral neuropathy. The prophylactic administration of pyridoxine prevents neuropathy.

RIFAMPIN, RIFABUTIN, AND RIFAPENTINE

Unlike isoniazid, the rifamycins are active against a broad spectrum of bacteria. These agents, which inhibit bacterial RNA polymerase, are discussed in more detail in the “Rifamycins” section. Mycobacteria readily become resistant to rifamycins when they are used as monotherapy. Resistance is the result of mutations in the gene that encodes RNA polymerase.

PYRAZINAMIDE

Like isoniazid, pyrazinamide targets an enzyme essential for the synthesis of mycolic acid. This agent only kills mycobacteria at acidic pH. Fortunately, intracellular M. tuberculosis resides within an acidic phagosome. Consequently, this drug is active against intracellular organisms. Resistance results from mutations in the gene encoding pyrazinamidase, an enzyme essential for converting pyrazinamide into its active form. Adverse effects include hepatotoxicity and elevated serum levels of uric acid, which may lead to gout.

ETHAMBUTOL

Ethambutol targets an enzyme involved in the synthesis of the mycobacterial cell wall. Mutations in the gene encoding this enzyme result in resistance. The major toxicity is optic neuritis, which may lead to decreased visual acuity and red–green discrimination.

CLARITHROMYCIN AND AZITHROMYCIN

Clarithromycin and azithromycin prevent protein translation by targeting the ribosomes of many different bacteria, including some mycobacteria. These agents are discussed in more detail in the “Macrolides” section.

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Several antibiotics are active against mycobacteria. Some of these agents, such as isoniazid, are used specifically to treat mycobacterial infections, whereas other agents, such as rifampin, show activity against a broad range of bacterial genera. Because mycobacteria are prone to develop resistance to antimicrobial compounds and are difficult to eradicate, treatment regimens usually contain multiple agents and continue for months.

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