Infectious diseases specialists diagnose and treat infections from bacteria, viruses, fungi, and parasites, focusing on fevers, antibiotics, and vaccines.
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The treatment of active tuberculosis is a rigorous, extended process guided by the principles of multidrug chemotherapy. The rationale for using multiple antibiotics simultaneously is twofold: first, to ensure rapid killing of actively replicating bacteria and render the patient non-infectious; and second, to eliminate dormant or slow-growing persisters and prevent relapse and the emergence of drug resistance. Mycobacterium tuberculosis has a high mutation rate, and using a single drug would inevitably select for resistant mutants. By combining drugs with different mechanisms of action, the probability that bacteria will simultaneously develop resistance to all of them is statistically negligible.
Standard treatment for drug-susceptible TB is divided into two distinct phases: the Intensive Phase and the Continuation Phase.
The standard course lasts six months. However, for extrapulmonary cases involving bones or the central nervous system, treatment duration is often extended to 9-12 months or longer to ensure adequate penetration and sterilization of these difficult-to-reach sites.
Understanding the mechanisms of the core drugs highlights the complexity of the regimen.
The rise of Multidrug-Resistant TB (MDR-TB) and Extensively Drug-Resistant TB (XDR-TB) presents a massive challenge. MDR-TB is defined by resistance to at least Isoniazid and Rifampicin, the two most potent drugs. Treatment for MDR-TB is far more complex, toxic, and lengthy, often requiring 9 to 24 months of therapy.
Management involves second-line agents, which are generally less effective and more likely to cause side effects. These include fluoroquinolones (e.g., levofloxacin, moxifloxacin), injectable agents (e.g., amikacin), and newer drugs explicitly developed for resistant strains, such as bedaquiline and delamanid. Bedaquiline, for instance, targets the bacterial ATP synthase, cutting off the pathogen’s energy supply. The regimen is tailored to the patient’s strain’s specific resistance profile.
Adherence to the lengthy TB regimen is the single most critical factor in cure and prevention of resistance. To address this, the World Health Organization promotes the DOTS (Directly Observed Treatment, Short-course) strategy. This involves a trained health worker or a designated community member observing the patient swallow their medication with every dose (or at least during the intensive phase). This strategy shifts the responsibility for care from the patient to the healthcare provider. Modern adaptations include Video Observed Therapy (VOT), utilizing smartphone technology to monitor adherence remotely, offering patients more flexibility while maintaining supervision.
Monitoring for Toxicity and Side Effects
TB medications carry a risk of significant side effects, necessitating careful clinical and biochemical monitoring.
While antibiotics clear the infection, the aftermath of TB often leaves the lungs with cavities, fibrosis, and bronchiectasis (damaged airways). Management extends beyond sterilization to supporting lung recovery. This includes pulmonary rehabilitation to improve respiratory mechanics and nutritional support to repair the metabolic wasting caused by the disease.
Current research in regenerative medicine investigates ways to mitigate the post-TB lung damage. This involves studying how to modulate the immune response to reduce excessive inflammation and fibrosis during treatment. The concept is to use host-directed therapies that not only help the immune system kill bacteria but also promote the resolution of inflammation, preserving lung architecture and, where possible, utilizing the lung’s intrinsic progenitor cells to repair alveolar damage.
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TB treatment is lengthy because the bacteria grow slowly and can enter a dormant state in which they are metabolically inactive. Most antibiotics work best on actively dividing cells. Therefore, a long duration is required to ensure that the drugs are present when these dormant bacteria periodically “wake up,” providing complete eradication and preventing relapse.
Missing doses allow the bacteria to replicate again. More dangerously, it exposes the bacteria to sublethal levels of the drug, which promotes the survival of the strongest, most resistant mutants. This can lead to drug-resistant TB, which is much harder to cure, requires more toxic drugs, and takes much longer to treat.
One of the primary TB drugs, Isoniazid, interferes with the body’s metabolism of Vitamin B6 (pyridoxine). A deficiency in this vitamin can damage peripheral nerves, leading to numbness, tingling, or pain in the hands and feet. Taking a supplemental dose of Vitamin B6 prevents this neurological side effect.
It is strongly advised to avoid alcohol during TB treatment. The primary TB drugs place a significant strain on the liver. The liver also processes alcohol and is hepatotoxic. Combining the two significantly increases the risk of severe drug-induced liver injury or hepatitis, which could force the discontinuation of life-saving treatment.
DOTS stands for Directly Observed Treatment, Short-course. It is the internationally recommended strategy for TB control. It ensures that patients take the right drugs, in the proper doses, at the appropriate intervals, by having a health worker or support person watch the patient swallow their medication. This guarantees adherence and helps prevent the spread of the disease and the development of drug resistance.
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