A patient with latent TB will give a positive TB skin test (mantoux test) but show no clinical signs of the disease.  Their TB can be treated with Isoniazid given for 9 months.  Remember that TB treatments are long because the bacteria is slow-growing.

While isoniazid is the drug of choice for latent TB, remember that the alternative drug is rifampin (in cases of INH resistance or contraindication)

For someone with active tuberculosis, there are 2 phases of treatment: the Initial phase and the Continuous phase.

Initial treatment is with 4 drugs: "ripe"  Rifampin, Isoniazid, Pyrazinamide, and Ethambutol

This treatment is given for 2 months before administering the continuous phase of treatment

Isoniazid is only effective against M. tuberculosis and some atypical mycobacteria.

it is NOT effective against MAC or M. leprae

Isoniazid is converted by acetylation to acetylisoniazid.  This is then metabolized to further intermediates, one of them (acetylhydrazine) being hepatotoxic!

Recall the importance of fast and slow acetylators.  Some people are naturally fast acetylators and will reduce the plasma levels of isoniazid faster, as well as increase the accumulation of the hepatotoxic metabolite!

Isoniazid is also neurotoxic, and slow acetylators will have increased risk of this because the isoniazid stays in the plasma for longer with them.  (treat/prevent with vitamin B6)

Isoniazid can also cause anemia & thrombocytopenia

Rifampin is a broad spectrum antibiotic that inhibits the beta subunit of bacterial RNA polymerase (Recall: isoniazid, because it targets mycolic acid synthesis, acts only against mycobacteria).

Rifampin acts against gram positive, gram negative, and acid fast bacteria!

Specifically, rifampin acts on M. tuberculosis and M. leprae.  It is also added to combination therapy for the treatment of staphylococcal endocarditis.

Rifampin can turn the patient's urine, sweat, and tears an orange-red. 

Other adverse effects include flu-like symptoma and hepatitis.

(all RIPES except streptomycin can cause hepatitis)

Rifampin induces liver microsomal enzymes, thereby decreasing the potency of other drugs metabolized by this system. 
For example, rifampin decreases the effect of oral contraceptives, which can lead to unwanted pregnancies.  It also decreases the potency of antiepileptic drugs, which can lead to seizures.  NNRTI treatment in HIV patients is also negatively impacted.

ALso remember the other classic examples such as theophylline, warfarin, and phenytoin.

Because these have a narrow therapeutic index, a decrease in their plasma concentration can more easily lead to therapeutic failure (just as an increase can more easily lead to toxicity)

Bacteria acquire resistance to rifampin by decreasing the affinity of their RNA polymerase for the drug.

This occurs mainly through methylation of the RNA polymerase.

Pyrazinamide is an effective drug against M. tuberculosis. It is converted by the bacteria to pyrazinoic acid, which lowers the pH to a level that inhibits bacterial growth.

It is considered a bactericidal drug.

Ethambutol inhibits the enzyme arabinosyl transferase, thereby stopping the production of arabinogalactan, a component of the bacterial cell wall.

Ethambutol is the one first line drug that is considered bacteriostatic.  It can be used in the treatment of MAC!

Remember: ethambutol is one of the RIPES drugs, and a first line agent against TB.
It disrupts arabinogalactan synthesis, leading to cell wall permeability.

Ethambutol may cause hepatitis, hyperuricemia, optic neuritis, and thrombocytopenia.

optic neuritis is inflammation of the optic nerve, which leads to a decrease in visual accuity or even total blindness!

Cycloserine is a cell wall inhibitor.  It acts as an analog to D-ala and inhibits the incorporation of D-ala into the pentapeptide during PG synthesis.

Side effects include psychosis and peripheral neuropathy.

Disseminated MAC (M. avium-intracellulare complex) infections are seen most commonly in patients with AIDS or a depressed immune system.

Recall that Rifabutin is used instead of Rifampin to treat MAC infections.  This is because this infection is more common in AIDS patients.  Rifampin induces CYP450 enzymes thereby reducing the efficacy of other co-administered drugs.  Of particular importance here would be decreased efficacy of protease inhibitors and NNRTIs, crucial components of anti-retroviral therapy.  Rifabutin does not have the same effect on the CYP450 system as Rifampin, which is why it is used instead.

To prevent the development of MAC infection, "CAR" is administered to the HIV+ patient.  Clarithromycin, Azithromycin, Rifabutin.

"a MAC truck is a type of CAR"

Dapsone, like sulfonamides, can cause hemolytic anemia in G6PDH deficient patients.

It can also cause GI disturbance, neuropathy, nephrotic syndrome, and lupus-like reactions.

clofazimine is a bactericidal drug against M. leprae. It is also effective against the other mycobacteria M. tuberculosis and MAC!!

Additionally, clofazimine has anti-inflammatory effects and is used to treat Erythema Nodosum Leprosum ( a side effect of antileprosy therapy produced by the lysis of leprae bacteria)

ENL is managed by the drug clofazimine.  Thalidomide can also be used to manage ENL.

Clofazimine is used in the multi-drug treatment of leprosy involving Rifampicin, Dapsone, and Clofazimine.  It has an anti-inflammatory effect, which is beneficial in ENL treatment.  Side effects include a pink/brown skin discoloration and myelosuppression.

Clofazimine is a drug used in the treatment of leprosy.  Remember it also has an anti-inflammatory action and can help with mild Erythema nodosum leprosum.  75-100% of patients on clofazimine suffer skin pigmentation (pink-brownish black discoloration)

They also suffer GI intolerance.

ENL is an antibody- immune complex reaction.  It results from a reaction to mycobacterial antigens released upon lysis of the bacteria during therapy.  It is characterized by painful nodules and plaques. 

Thalidomide is the treatment of choice for severe forms.  Less severe forms can be treated with clofazimine and corticosteroids.