Antibiotics - Antimycobacterials: Nursing Pharmacology

Antimycobacterials are medications used to treat infections caused by the mycobacterium species. These include tuberculosis, caused by Mycobacterium tuberculosis; leprosy, also known as Hansen’s disease, caused by Mycobacterium leprae; and non-tuberculous lung infections caused by Mycobacterium avium complex or MAC, which includes Mycobacterium avium, Mycobacterium chimaera, and Mycobacterium intracellulare.

Antimycobacterial drugs can be divided into two broad categories. We have the first-line antimycobacterials, which are the standard initial therapy; and the second-line antimycobacterials, used when the first-line drugs aren’t suited, like when they have contraindications, they have failed to treat the infection, or with multi-drug resistant tuberculosis.

The first-line antimycobacterials include isoniazid or INH for short, which is administered orally or intramuscularly; as well as streptomycin or SM, which is given intravenously or intramuscularly; rifampin or RIF, which is given orally and intravenously; and rifapentine or RPT, ethambutol or EMB, and pyrazinamide or PZA, all of which are given orally.

On the other hand, the second-line antimycobacterials include bedaquiline, cycloserine, ethionamide, rifabutin, and aminosalicylic acid all of which are administered orally; as well as capreomycin which is administered intravenously or intramuscularly; and amikacin which can be administered intravenously, intramuscularly, or by inhalation. These medications are mainly used for treating active mycobacterial infections, except rifabutin, which is preferred as preventive treatment against Mycobacterium Avium complex in clients with advanced HIV infection, who are severely immunocompromised. Finally, antimycobacterials also include leprostatic medications, such as dapsone, which is administered orally to treat leprosy.

Now, antimycobacterials have different mechanisms of action by targeting various mycobacterial structures. Isoniazid, ethambutol, aminosalicylic acid, ethionamide, and cycloserine act mainly by disrupting the synthesis of essential components of the bacterial cell walls, which causes bacteria to burst out of osmotic pressure, and die.

On the other hand, rifampin, rifapentine, and rifabutin work by inhibiting the bacterial DNA-dependent RNA polymerase, which prevents the bacteria from synthesizing RNA, ultimately killing them. Next, streptomycin, amikacin, and capreomycin work by inhibiting bacterial ribosomes, stopping protein synthesis.

There is also bedaquiline, which inhibits the synthesis of bacterial ATP, making them run out of energy needed for their metabolic functions, and then ultimately die. The mechanism of action of some medications like pyrazinamide isn’t fully understood, but it is thought to interfere with bacterial fatty acid synthesis, which is needed for their growth. Finally, dapsone works by inhibiting the pathway of folic acid, ultimately disrupting bacterial proliferation.

Unfortunately, antimycobacterial medications can cause undesired side effects, ranging from mild side effects requiring dose adjustment and careful monitoring, to serious organ damage, which can require immediate discontinuation.

Clients taking antimycobacterials may present with gastrointestinal side effects, which include nausea, vomiting, anorexia, stomach upset, and abdominal pain. Other side effects include hypersensitivity reactions, ranging from skin rashes or hives to life-threatening anaphylaxis. This can occur with any of the antimycobacterial medications, but it is more commonly seen in isoniazid, rifampicin, pyrazinamide, ethionamide, cycloserine, ethambutol, aminosalicylic acid, and streptomycin.

Some of these medications can also cause neurotoxicity, most often associated with isoniazid, which is associated with peripheral neuropathy, optic neuritis, memory impairment, and agitation; ethambutol, which can cause optic neuritis, decreased visual acuity, or color blindness; capreomycin and amikacin, which have a boxed warning for ototoxicity; cycloserine which can cause confusion, depression, psychosis, and seizures; ethionamide, which can cause optic neuritis; as well as streptomycin, which has a boxed warning for neurotoxicity that can manifest as peripheral neuropathy, ototoxicity, and toxicity to the optic nerve. Clients on antimycobacterials can also develop hepatotoxicity, which is a boxed warning for isoniazid.

Next, bedaquiline has a boxed warning for QT prolongation; dapsone can cause hematological problems like hemolytic anemia, aplastic anemia, and agranulocytosis; while rifabutin can cause neutropenia. Nephrotoxicity is a side effect of ethambutol and capreomycin, and a boxed warning for amikacin. Finally, rifampin, rifapentine, and rifabutin can turn certain body fluids like urine, tears, and saliva a reddish-orange color.

As far as interactions with other medications are concerned, rifampin, rifapentine, and rifabutin are notable for their ability to induce a number of cytochrome P450 isoenzymes, meaning that by accelerating the metabolism of other medications, rifampin reduces the effectiveness of medications like warfarin, oral contraceptives, and medications used to treat HIV infection.