Antimycobacterial drugs
The most common mycobacterial infections globally are tuberculosis (TB) and leprosy.
Tuberculosis is a bacterial infection caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs, but can also affect other parts of the body. According to the World Health Organization (WHO), there were an estimated 10 million cases of TB worldwide in 2020, with the highest burden of disease in Asia and Africa.
Leprosy (or Hansen's disease) is a chronic bacterial infection caused by Mycobacterium leprae. It primarily affects the skin and peripheral nerves, but can invade other organs and tissues. WHO data from 2020 indicate that the highest burden of disease is in India, Brazil, and Indonesia.
Other less common mycobacterial infections include nontuberculous mycobacterial infections (e.g., M. kansasii, M. marinum, M. ulcerans and M. xenopi), and M. avium complex (MAC) infections that primarily affect people with weakened immune systems.
Several drugs are currently in clinical use for the treatment of these infections. These drugs differ in their mechanisms of action and prescribing information. Summarized details for each medication are provided below.
- Isoniazid is a first-line antituberculosis drug that works by inhibiting mycolic acid synthesis, a critical component of the mycobacterial cell wall. It is administered orally and is generally well-tolerated. However, it can cause hepatotoxicity and peripheral neuropathy, especially in patients with underlying liver disease or diabetes.
- Rifampin is another first-line orally administered antituberculosis drug. It acts to inhibit bacterial DNA-dependent RNA polymerase activity. Rifampin is bactericidal against M. leprae and it is the main constituent of multiple-drug regimens used for treatment of leprosy; other drugs are included in the regimens to prevent emergence of rifampin-resistant M. leprae. Can be used (off-label) for the treatment of MAC pulmonary infections in conjunction with other antimycobacterials. Rifampin can cause a number of side effects, including hepatotoxicity, gastrointestinal disturbance, and hematologic effects that can include thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.
- Pyrazinamide is a first-line antituberculosis drug that works by disrupting the energy metabolism of mycobacteria. It is administered orally and can cause hepatotoxicity and hyperuricemia.
- Ethambutol is a second-line antituberculosis drug that works by inhibiting bacterial cell wall synthesis. It is administered orally and can cause optic neuritis, which can lead to vision loss.
- Streptomycin is an aminoglycoside antibiotic that is used in combination with other antituberculosis drugs to treat multidrug-resistant TB. It inhibits bacterial protein synthesis. It is administered intramuscularly and can cause ototoxicity and nephrotoxicity.
- Dapsone is used to treat leprosy as a component of multidrug therapies (MDT). MDT regimens can quickly clear the infection, reduce the risk of transmission, and delay or prevent emergence of resistant M. leprae. A two-medicine MDT (dapsone and rifampicin) is used to treat paucibacillary (or tuberculoid) leprosy and a three-drug MDT (dapsone, rifampicin and clofazimine) to treat multibacillary (or lepromatous) leprosy.
The World Health Organization (WHO) Essential Medicines List (EML) includes several antimycobacterial drugs that are considered essential for the treatment of tuberculosis (TB) and other mycobacterial infections. These drugs are included in the EML because they are effective, safe, and affordable, and are essential for addressing global health needs.
Links to the online EML lists of TB and leprosy drugs: