Management of MDR and XDR Tuberculosis: An Overview

Introduction:

Tuberculosis (TB) is an infectious disease caused by bacteria. The disease can transfer from person to person through the air. When a person who has TB sneezes or coughs, the bacteria is expelled into the air. This TB bacteria gets inhaled by a healthy individual, causing a new infection. TB mostly affects the lungs but can also affect the brain, kidneys, or spine. TB is usually curable, but if treatment is not received, patients may not recover from the infection, which may lead to life-threatening complications. Drug-resistant tuberculosis can occur when the bacteria causing TB develop resistance to the medication used to treat TB. Due to this resistance, the medication can no longer kill this bacteria. TB and drug-resistant TB (DR TB) are transmitted in the same ways. Drug resistance TB is of two types: Multidrug-resistant TB (MDR TB) and Extensively drug-resistant TB (XDR TB). This article focuses on the management of MDR and XDR tuberculosis.

What Is MDR Tuberculosis?

Isoniazid and Rifampicin are the two main drugs used to treat tuberculosis. These medicines kill the bacteria causing TB. In multidrug-resistant (MDR) TB, these bacteria may become resistant to these drugs, making the medicine ineffective in treating TB. MDR tuberculosis is caused by mismanagement of TB treatment. The majority of TB patients get cured by strictly adhering to a six-month drug regimen given to them under supervision. Drug resistance can develop as a result of improper or inappropriate use of antibiotics, ineffective drug formulations such as single drugs, low-quality medications, improper storage conditions, and early treatment discontinuation.

What Is XDR Tuberculosis?

Extensively drug-resistant TB (XDR TB) is a more severe form of drug resistance. XDR TB is not only resistant to Isoniazid and Rifampicin but also resistant to other antibiotics that are backup options to treat TB, such as Fluoroquinolone, and second-line injectable drugs such as Mikacin, Kanamycin, and Capreomycin. Since XDR TB is resistant to potent TB medications, patients are left with less effective treatment options. Individuals with weak immune systems, like those with HIV (human immunodeficiency disease) or other conditions. Such individuals are at increased risk of developing TB and a higher risk of dying from the disease.

What Is the Management of MDR and XDR Tuberculosis?

1. Assessment Before Treatment of MDR and XDR Tuberculosis: Before designing a treatment for drug-resistant tuberculosis, DST (drug susceptibility testing) is done to determine which TB drug a bacterial strain is resistant to DTS is important to choose the most appropriate and effective treatment for MDR and XDR Tuberculosis.

2. Treatment Approach:

• Standardized Treatment: This approach uses DRS (drug resistance surveillance) data without DST. All patients in the defined category get the same treatment.

• Individualized Treatment: This treatment approach is based on the patient's history of TB treatment and DST results.

• Empiric Treatment: This approach involves treating the patients before the diagnosis is confirmed. This can be done either with standardized treatment or an individualized treatment approach.

3. Anti-TB Drugs Used in MDR Management:

• Group 1 (First-Line Oral Agents): Group 1 includes Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. These drugs are the well-tolerated and most effective drugs for MDR TB.

• Group 2 (Injectable Anti-TB Drugs): Group 2 injectable anti-TB drugs include Kanamycin, Amikacin, or Capreomycin. During the intensive treatment phase, all MDR-TB patients should receive group 2 drugs unless tests detect resistance or there is a strong suspicion of it.

• Group 3 (Fluoroquinolones): In the MDR-TB regimen, Fluoroquinolones are regarded as the most potent drug. They help to increase cure rates for MDR-TB and have shown improvements in treating the disease. Studies have shown that later-generation Fluoroquinolones (such as Moxifloxacin and Levofloxacin ) have greater efficacy than earlier-generation Fluoroquinolones (such as Ofloxacin).

• Group 4 (Oral Bacteriostatic Second-Line Anti-TB Drugs): Group 4 anti-TB drugs are important drugs used in the treatment of MDR-TB. Group 4 drugs include Ethionamide, Prothionamide, Cycloserine, and Para-aminosalicylic acid(PAS).

• Group 5: Group 5 drugs include Bedaquiline, Linezolid, Clofazimine, and Clarithromycin. The WHO does not advise using Group 5 drugs routinely in the treatment of MDR-TB because of the quality of evidence about their safety and effectiveness in humans. But when it is not possible to create a successful treatment plan using drugs from group one to group 4, they become a valuable choice.

4. Treatment of XDR-TB: XDR-TB is the more resistant form of MDR-TB. It is estimated that XDR-TB occurs in 9.6 percent of the patients with MDR-TB. Treatment considerations include:

• Studies have shown that using at least six drugs in the intensive phase and four in the continuous phase could increase the success rate.

• Even if they show resistance to tests, later-generation fluoroquinolones significantly improve treatment outcomes.

• Bedaquiline, a new drug, is designed for XDR-TB patients.

For newly diagnosed MDR-TB, the total duration of treatment is 20 months for the majority of the patients. For previously treated MDR-TB, including XDR-TB, the treatment duration is often longer, at least 24 months.

General Principles of Treatment: Early detection and appropriate treatment initiation are essential for successful results. The initial phase of MDR-TB treatment should involve at least four second-line anti-TB drugs and also Pyrazinamide. MDR regimens should include the following:

• Pyrazinamide.

• Injectable anti-TB drugs.

• Fluoroquinolone (later generation preferred).

• Ethionamide or Prothionamide (provided there is no contraindication).

• Cycloserine or PAS (if Cyclosporin cannot be used).

• There are conditions like XDR-TB where more than five drugs are used.

• The duration of the intensive phase, which is the first portion of treatment and involves the use of a Group 2 injectable drug, is at least eight months. However, it may be adjusted based on the patient's response to treatment.

• Close monitoring and management of side effects is essential.

• Directly observed therapy is needed to ensure the patient takes medication correctly.

• Antiretroviral therapy should be given to HIV-positive patients with drug-resistant TB.

• Dosing is based on weight and age.

• The total duration of newly diagnosed MDR-TB is 20 months.

• Pyrazinamide can be continued throughout the treatment.

• Isoniazid is given initially until DST results are available.

• For patients with MDR-TB, ambulatory care is preferred over hospitalization.

Conclusion:

Managing MDR-TB and XDR-TB is complex; it requires a multidimensional approach, including early diagnosis, customized treatment regimens, and infection control measures. Ongoing research offers hope for effective management of drug-resistant TB and improving patient outcomes.