7.5 Introduction to Tuberculosis and Antitubercular Drugs

Tuberculosis Pathophysiology and Diagnosis

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily targets the lungs and remains one of the leading infectious disease killers worldwide. For nurses, understanding how TB develops, how it's diagnosed, and how it's treated is essential because TB management depends heavily on patient education, medication adherence, and monitoring for serious drug side effects.

Pathophysiology of Tuberculosis

TB spreads through airborne droplet nuclei released when an infected person coughs, sneezes, or even speaks. Once inhaled, M. tuberculosis reaches the alveoli and gets engulfed by alveolar macrophages. Here's what makes TB tricky: the bacteria survive and replicate inside those macrophages rather than being destroyed by them.

The immune system walls off the infection by forming granulomas, which are clusters of immune cells surrounding the bacteria. In many people, the bacteria stay trapped in these granulomas indefinitely. This is latent tuberculosis infection (LTBI), where the person is infected but asymptomatic and not contagious.

If the immune system weakens (from HIV, malnutrition, immunosuppressive drugs, etc.), those granulomas can rupture, releasing bacteria into the lung tissue and potentially into the bloodstream. This leads to active TB, which can also spread beyond the lungs to lymph nodes, bones, kidneys, and meninges (extrapulmonary TB).

Active TB symptoms include:

• Chronic productive cough lasting longer than 2–3 weeks
• Hemoptysis (coughing up blood)
• Fever, night sweats, and unintentional weight loss
• Chest pain and dyspnea (shortness of breath)

Diagnostic Methods for Tuberculosis

No single test confirms TB on its own. Diagnosis typically involves a combination of screening tests, imaging, and microbiological confirmation.

Tuberculin Skin Test (TST / PPD Test)

• An intradermal injection of purified protein derivative (PPD) is placed on the forearm
• The site is read 48–72 hours later by measuring the area of induration (hardness), not redness
• A positive result indicates TB exposure but does not distinguish between latent and active disease
• False positives can occur in people who received the BCG vaccine

Interferon-Gamma Release Assays (IGRAs)

• Blood tests (such as QuantiFERON-TB Gold) that measure the immune response to TB-specific antigens
• More specific than the TST because results are not affected by prior BCG vaccination
• Also cannot distinguish latent from active TB

Chest X-ray

• Shows characteristic findings in active pulmonary TB, including cavities or infiltrates, typically in the upper lung lobes
• Used to follow up on a positive TST or IGRA

Sputum Smear and Culture

• Sputum samples are stained for acid-fast bacilli (AFB) using the Ziehl-Neelsen method
• Culture is the gold standard for confirming active TB, though results can take 2–6 weeks

Nucleic Acid Amplification Tests (NAATs)

• Rapid molecular tests (such as GeneXpert) that detect M. tuberculosis DNA directly from sputum
• Can provide results within hours and can also identify rifampin resistance, which is a marker for drug-resistant TB

Antitubercular Drugs and Treatment

TB treatment requires multiple drugs taken for months. This combination approach exists for two reasons: it prevents the development of drug resistance, and different drugs target bacteria in different metabolic states (actively dividing, dormant inside granulomas, etc.).

Classes of Antitubercular Drugs

First-Line Drugs (the standard regimen for drug-susceptible TB):

Second-Line Drugs (reserved for drug-resistant TB or intolerance to first-line agents):

• Fluoroquinolones (levofloxacin, moxifloxacin) inhibit DNA gyrase and topoisomerase IV
• Aminoglycosides (amikacin) and capreomycin inhibit bacterial protein synthesis
• Ethionamide inhibits mycolic acid synthesis (similar mechanism to INH)
• Cycloserine inhibits bacterial cell wall synthesis

Side Effects of Antitubercular Medications

Each first-line drug has a signature side effect profile you need to know:

Isoniazid (INH)

• Hepatotoxicity (most concerning; monitor LFTs)
• Peripheral neuropathy due to pyridoxine (vitamin $B_6$) depletion. Supplemental $B_6$ is routinely co-prescribed to prevent this.
• Drug-induced lupus-like syndrome (rare)
• Significant interactions with phenytoin, carbamazepine, and warfarin (INH inhibits their metabolism)

Rifampin (RIF)

• Hepatotoxicity
• Orange-red discoloration of urine, tears, sweat, and saliva (harmless but patients need to know so they don't panic; warn contact lens wearers about permanent staining)
• Flu-like symptoms
• Potent inducer of cytochrome P450 enzymes, which means it speeds up the metabolism of many other drugs, including oral contraceptives, warfarin, HIV protease inhibitors, and methadone. This is one of the most clinically significant drug interactions in pharmacology.

Pyrazinamide (PZA)

• Hepatotoxicity
• Hyperuricemia (elevated uric acid), which can trigger gout-like joint pain (arthralgia)

Ethambutol (EMB)

• Optic neuritis, which presents as decreased visual acuity and difficulty distinguishing red from green. Baseline and monthly visual acuity and color vision testing are required.

Second-Line Drug Side Effects

• Fluoroquinolones: QT prolongation, tendinopathy, CNS effects
• Aminoglycosides: ototoxicity (hearing loss) and nephrotoxicity
• Ethionamide: GI disturbances and hypothyroidism

First-Line vs. Second-Line Antitubercular Drugs

The memory aid RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethambutol) is commonly used to recall the four first-line drugs.

Nursing Considerations for Antitubercular Drugs

1. Before starting therapy, assess for contraindications such as pre-existing liver disease, visual impairment (for ethambutol), or known drug allergies. Obtain baseline liver function tests (LFTs), complete blood count, serum uric acid, and visual acuity testing.

2. Monitor hepatotoxicity closely. Three of the four first-line drugs (INH, RIF, PZA) are hepatotoxic. Teach patients to report jaundice, dark urine, abdominal pain, or unusual fatigue immediately. Periodic LFT monitoring is standard.

3. Administer medications correctly. Rifampin should be taken on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. The other first-line drugs can be given with food if GI upset occurs.

4. Co-prescribe pyridoxine (vitamin $B_6$) with isoniazid to prevent peripheral neuropathy, especially in patients at higher risk (diabetics, malnourished patients, pregnant women, those with HIV).

5. Screen for drug interactions, particularly with rifampin. Patients on oral contraceptives need an alternative or additional method of birth control. Review all current medications before starting therapy.

6. Implement Directly Observed Therapy (DOT) when possible. DOT means a healthcare worker watches the patient swallow each dose. This is the single most effective strategy for ensuring adherence and preventing drug resistance.

7. Maintain infection control. Patients with active pulmonary TB require airborne isolation precautions (negative-pressure room, N95 respirators for healthcare workers) until they have three consecutive negative sputum AFB smears.

8. Encourage avoidance of alcohol throughout treatment to reduce the additive risk of hepatotoxicity.

Patient Education for Tuberculosis Treatment

• Adherence is critical. Stopping medications early or skipping doses is the primary driver of drug-resistant TB. Even when symptoms improve (often within a few weeks), the full 6-month course must be completed.
• Report signs of liver damage (jaundice, dark urine, nausea, abdominal pain) or visual changes (blurred vision, color blindness) right away.
• Expect orange-red discoloration of body fluids with rifampin. This is normal and not harmful, but it will permanently stain soft contact lenses.
• Inform all healthcare providers (including dentists) about TB treatment so they can check for drug interactions.
• Practice respiratory hygiene: cover coughs, dispose of tissues properly, and ventilate living spaces. Patients are generally considered non-infectious after 2–3 weeks of effective treatment with documented clinical improvement.
• Attend all follow-up appointments. Sputum cultures are repeated to confirm the treatment is working.

Global TB Control and Prevention

The World Health Organization (WHO) coordinates global TB elimination efforts. TB remains the leading cause of death from a single infectious agent worldwide, surpassing even HIV.

Multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampin, is a growing threat. Extensively drug-resistant TB (XDR-TB) adds resistance to fluoroquinolones and at least one injectable agent, making treatment even more difficult.

The Bacille Calmette-Guérin (BCG) vaccine is widely used outside the United States to prevent severe disseminated TB and TB meningitis in children. It does not reliably prevent pulmonary TB in adults, which is why it's not part of the routine U.S. vaccination schedule.

Global strategy centers on early detection, effective treatment with DOT, infection control, and development of new drugs and vaccines to address drug-resistant strains.