Mycobacteria, the group of bacteria that contain the pathogens that cause

tuberculosis and leprosy, are classified on the basis of their ability to hold a stain
even the presence of destaining agent such as acid. Because of this property, they
are called “fast acid bacteria”. The mycobacteria have an outer coat of mycolic acid
that protects them from many disinfectants and allows them to survive for long
periods in the environment. These slow growing bacteria may need to be treated for
several years before they can be eradicated.

Mycobacteria cause serious infectious diseases. The bacterium

Mycobacterium tuberculosis cause tuberculosis, the leading cause of death from
infectious disease in the world. For several years the disease was thought to be
under control, but with the increasing number of people with compromised immine
systems and the emergence of resistant bacterial strains, tuberculosis is once again
on the rise.

Mycobacterium leprae causes leprosy, also known as Hansen’s disease, which

is characterized to disfiguring skin lesions and destructive effects on the respiratory
tract. Leprosy is also a worldwide health problem; it is infectious when the
mycobacteruym invade the skin or respiratory tract of susceptible individuals.
Mycobacterium avium-intracellulare which causes mycobacterium avium complex
(MAC), is seen in patients with AIDS or in other patients who are severely
immunocompromised. Rifabutin (Mycobutin) which was developed as an
antituberculosis drug, is most effective agaisnt M. Avium intracelulare.

Antituberculosis drug

Tuberculosis can lead to serious damage in the lungs, the GU tract, bones and the
meninges. Because M. Tuberculosis is so slow growing, the treatment muct be
continued for 6 months to 2 years. The first- line drugs for treating tuberculosis are
as follows:

• Isoniazid (INH) (Nydrazids) which affects the mycolic acid coating of the
bacterium
• Rifampin (Rifadin, Rimactane) which alters DNA and RNA activity in the
bacterium.
• Ethionamide (Trecator SC) which prevents cell division
• Rifapentine (Priffin), which alters DNA and RNA activity causing cell death.

These drugs are used in combination of two or more more agents until bacterial
conversion occurs or maximum improvent is seen.

If the patient cannot take one or more of these drugs, or if the disease
continues to progress because of the emergence of a resistant strain, the cond-line
drugs can be used:

• Ethambutol (Myambutol) which inhibits cellular metabolism

 • Pyrazinamide (generic) which is both bactericidal and bacteriostatic

These drugs are used in combination with at least one other antituberculosis
drug. If therapeutic success is still not achieved, a third line combination of two
antituberculosis drugs can be tried

• Capreomycin (Capastat), whose mechanism of action is unknown

• Cycloserine (Seromycin) which inhibits cell all synthesis and lead to cell
death
Using the drugs in combination, helps to decrease the emergence of
resistant strains and to affect the bacteria at various phases during their
long and slow life cycle.

Leprostatic Drug

Antibiotics used to treat leprosy include dapsone and clofazimine. Dapsone

(generic) has been the mainstay of leprosy treatment for many years although
resistant strains are emerging. Similar to the sulfonamide, dapsone inhibits folate
synthesis in susceptible bacteria. In addition to tits use in leprosy, dapsone is used
to reat P. Carinii pnemonia in AIDS patients and for a variety of infections caused by
susceptible bacteria, as well as for brown recluse spider bites.

Ciofazimine (Lamprene), which binds to bacterial DNA sites and causes cell
death, has been useful in the treatment of dapsone-resistant leprosy. The drug is
used as part of the initial leprosy treatment in combination with dapsone to prevent
the development of resistant strains.

Recently, the hypnotic drug thalidomide (Thalomid) was approved in use for a
condition that ccurs after treatment for leprosy.

Therapeutic Action and Indication:

Most of the antimycobacterial agents act on the DNA of the bacteria leading to a
lack of growth and eventually to bacterial death. INH specifically affects the mycolic
acid coat around the bacterium. Although many of the antimycobacterial agents are
effective against other species of susceptible bacteria, their primary indications are
in the treatment of tuberculosis or leprosy. The antituberculosis drugs are always
used in the combination to affect the bacteria at various stages and to help to
decrease the emergence of resistant strains.

Pharmacokinetics

The antimycobacterial agents are generally well absorbed from the GI tract,
metabolized in the liver and excreted in the urine. Caution should be used in
patients with hepatic or renal dysfunction, which could interfere with the
metabolism and excretion of the drugs. These drugs cross the placenta and enter
breast milk; they should be avoided during pregnancy and lactation unless the
benefit to the mother clearly outweighs the potential risk to the neonate.

DRUGS IN FOCUS: ANTIMYCOBACTERIAL DRUGS

DRUG NAME DOSAGE/ ROUTE USUAL INDICATIONS

Antituberculosis Drugs
Capreomycin Adult: 1g/ d IM for 60 – 120 Second-line drug for treatment of
(Capastat) d; followed by 1g IM 2 – 3 Mycobacterium tuberculosis
times per week for 18 – 24
mo; reduce dosage with
renal impairment.
Pediatric: 15mg/kg per day
IM
Cycloserine Adult: 250g PO b.i.d for 2wk, Second-line drug for treatment of
(Seromycin) then 500 mg to 1g/d PO in Mycobacterium tuberculosis
divided dose.

Pediatric: safety not

established
Ethambutol Adult: 15mg/kg per day PO Second-line drug for treatment of
(Myambutol) as a single dose Mycobacterium tuberculosis
Pediatric: not recommended
for children <13y
ethionamide Adult: 15 – 20 mg/ kg per First-line drug for treatment of
(Trecator S.C.) day PO in divided doese with Mycobacterium tuberculosis
pyridoxine
Pediatric: 10 -20 mg/kg per
day PO individual doses with
pyridoxine
Isoniazid (INH) Adult: 5mg/kg per day PO First-line drug for treatment of
(Nydrazid) Pediatric: 10 – 20 mg/kg per Mycobacterium tuberculosis
day PO
Pyrazinamide Adult and pediatric: 15 – 30 Second-line drug for treatment of
(generic) mg/g per day PO Mycobacterium tuberculosis
Ritabutin Adult: 300 mg PO q.d. Treatment of Mycobacterium
(Mycobutin) Pediatric: safety not avium-intracellulare (MAC) in
established patients with advanced HIV
infection
Rifampin Adult: 600mg PO or IV as a First-line drug for treatment of
(Rifadin, single daily dose Mycobacterium tuberculosis
Rimactane) Pediatroc: 10 – 20 mg/kg per
day PO or IV
Rifapentine Adult: 600mg PO 2 times per First-line drug for treatment of
(Priffin) week for 2 mo Mycobacterium tuberculosis
Pediatric: safety not
 established
Leprostatic Drugs
Dapsone Adult: 50 – 100 mg/d PO Treatent of leprosy, Pneumocystis
(generic) Pediatric: 1 – 2 mg/kg per carinii pneumonia in AIDS
day PO for 3y patients, a variety of infections
caused by susceptible bacteria
and brown recluse spider bites
Clofazimine Adult: 100mg/ d PO for at Treatment for dapsone resistant
(Lamprene) least 2 y leprosy
Pediatric: safety not
established

Contraindications and Caution

Anitmycobacterial drugs are contraindicated for patients with any known allergy to
these agents; in those with severe renal or hepatic failure that could interfere with
the metabolism or excretion of the drug; in those with severe CNS dysfunction that
could be exacerbated by the actions of the drugs and in pregnancy because of
possible adverse effects on the fetus. If an antituberculosis regimen is necessary
during pregnancy, the combination of isoniazid, ethmabutol and rifampin is
considered the safest.

Adverse Effects

CNS effects such as neuritis, dizziness, headache, malaise, drowsiness and

hallucinations are often reported and are related to direct effects of the drugs on
the neurons. These drugs also are irritating to the GI tract, causing nausea,
vomitting, anorexsia, stomach upset, and abdominal pain. Rifampin, rifabutin and
rifapentine cause discoloration of the body fluids from urine to sweat to tears.
Patients should be alerted that in many instances orange-tinged urine, sweat and
tears may stain clothing and permanently stain contact lenses. This can be
frightening if the patient is not alerted to the possibility that it will happen. As with
other antibiotics, there is always a possibility of hypersensitivity reactions and the
patient should be monitored on a regular basis.

Clinically Important Drug to Drug Interaction

When rifampin and INH are used in combination, the possibility of toxic liver
reactions increases. Patient should be monitored closely.
Increased metabolism and decreased drug effectiveness occur as a result of
administration of quinidine, corticosteroid, oral contraceptives, oral antipropanolol,
oral anticoagulants, oral antidiabetic agents, digoxin, theophylline, methadone,
phenytoin, verapamil, cyclosporine, or ketoconazole, in combination with rifampin
or rifabutin. Patients who are taking these drug combinations should be monitored
closely and dosage adjustment as needed.
Nursing Managment’

Check culture and sensitivity reports. To ensure that this is the drug of choice
for this patient and arrange repeated cultures if response is not
anticipated.

Monitor renal and liver function test resilts before and periodically during therapy.
To arrange dosage reduction as needed.

Ensure that the patient receives the full course of the drugs. To improve
effectiveness and decrease the risk of development of resistand bacterial
strains. These drugs are taken for years and often in combination. Period
medical evaluation and reteaching are often essential to ensure
compliance.

Discontinue the drug immediately if hypersensitivity reactions occur. To avert

potentially serious reactions.

Encourage the patient to eat small, frequent meals as tolerated; perform frequent
mouth care and drink adequeate fluids to ensure adequate nutrition and
hydration. Monitor nutrition if GI effects become a problem.