Isoniazid in Treatment of Tuberculosis: A Guide

Introduction

Isoniazid ( INH) is a small molecule antibiotic and a principal component in the treatment of tuberculosis ( TB) infections. As a selective spectrum antibacterial agent with tuberculostatic properties, isoniazid is the drug of choice for managing the most common TB strains. This guide provides an overview of isoniazid and its use in combination therapy and monotherapy for treating active and latent TB in adults and children. ^[1]

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Mechanism of Action

Isoniazid works by inhibiting the synthesis of mycolic acids, essential components of the mycobacterial cell wall. This action leads to increased cell wall permeability and disruption of bacterial metabolism. ^[2]

armacokinetics/”>Ph armacokinetics and Ph armacodynamics

Isoniazid is rapidly absorbed orally and reaches peak serum concentrations within 1-2 hours. It exhibits excellent tissue penetration, including into the cerebrospinal fluid. The drug is metabolized primarily by the liver through acetylation and hydrolysis, with a half-life of 1-4 hours. ^[3]

Clinical Uses of Isoniazid

Indications for Use

Isoniazid is indicated for the treatment and prevention of TB infections caused by Mycobacterium tuberculosis. It is used in both active and latent TB infections in adults, children, and infants. ^[4]

Monotherapy for Latent TB Infection

Isoniazid monotherapy is the preferred treatment for latent TB infection (L TBI). The standard regimen is 5 mg/kg (maximum 300 mg) daily for 6-9 months. Isoniazid preventive therapy significantly reduces the risk of progression from L TBI to active TB disease. ^[5]

Combination Therapy for Active TB Infection

For active TB disease, isoniazid is used in combination with other anti-tubercular drugs, such as rifampin, pyrazinamide, and ethambutol. The standard 6-month RIPE regimen includes isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, followed by isoniazid and rifampin for the remaining 4 months. ^[6]

Treatment Regimens Involving Isoniazid

Standard Treatment Regimens

The 6-month RIPE regimen is the standard treatment for drug-susceptible TB. Alternative regimens include a 3-month regimen with isoniazid and rifampin for L TBI and a 4-month regimen with isoniazid, rifampin, and pyrazinamide for HIV-negative patients with non-cavitary pulmonary TB. ^[7]

High-dose and Short-course Regimens

High-dose isoniazid (16-18 mg/kg) in combination with rifapentine and moxifloxacin has been studied in short-course regimens for drug-susceptible TB. These regimens aim to reduce treatment duration while maintaining efficacy and safety. ^[8]

Isoniazid and Host Immune System Interactions

Impact on Immune Response

Isoniazid has been shown to modulate the host immune response to Mycobacterium tuberculosis. It enhances the bactericidal activity of macrophages and promotes the production of pro-inflammatory cytokines, such as TNF-α and IL-1β. ^[9]

Prevention of Mtb-induced Oxidative Stress

Isoniazid helps prevent oxidative stress mediated by Mycobacterium tuberculosis. By inhibiting the production of reactive oxygen species, isoniazid reduces tissue damage and improves the host’s ability to control the infection. ^[10]

Side Effects and Management

Common Side Effects

Common side effects of isoniazid include nausea, vomiting, loss of appetite, fatigue, and abdominal pain. These symptoms are usually mild and self-limiting. Rarely, isoniazid can cause severe adverse reactions, such as hepatotoxicity, neurotoxicity, and skin rash. ^[11]

Hepatotoxicity and Monitoring Liver Function

Isoniazid-induced hepatotoxicity is a serious concern, particularly in patients with pre-existing liver disease, alcohol abuse, or advanced age. Regular monitoring of liver function tests is recommended for patients on isoniazid therapy. If signs of hepatotoxicity develop, isoniazid should be discontinued promptly. ^[12]

Efficacy and Outcomes

Success Rates of Isoniazid Treatment

Isoniazid-based regimens have high success rates in the treatment of drug-susceptible TB. The 6-month RIPE regimen has a cure rate of over 95% in clinical trials. Isoniazid monotherapy for L TBI has an efficacy of 60-90% in preventing progression to active TB disease. ^[13]

Factors Influencing Efficacy

Factors that can influence the efficacy of isoniazid treatment include drug resistance, adherence to therapy, HIV co- infection, and the presence of cavitary lesions. Close monitoring, directly observed therapy (DOT), and management of comorbidities can help optimize treatment outcomes. ^[14]

Public Health and Socioeconomic Impact

Isoniazid in National TB Control Programs

Isoniazid is a key component of national TB control programs worldwide. Its use in preventive therapy and active disease treatment has contributed significantly to the reduction of TB incidence and mortality. Expanding access to isoniazid is crucial for achieving the global targets of the End TB Strategy. ^[15]

Patient Management and Counseling

Adherence Strategies

Ensuring patient adherence to isoniazid therapy is critical for successful treatment outcomes. Strategies to improve adherence include patient education, DOT, and the use of fixed-dose combination pills. Providing support and addressing socioeconomic barriers can also enhance treatment compliance. ^[16]

Future Directions and Research

New Developments in Isoniazid Use

Research efforts are focused on optimizing isoniazid-based regimens, particularly for drug-resistant TB. Novel combinations, such as isoniazid with newer drugs like bedaquiline and delamanid, are being explored to improve treatment outcomes and shorten therapy duration. ^[17]

References and Further Reading

1. Isoniazid: An Overview
2. Mechanisms of Action of First-Line Drugs Used in the Treatment of Tuberculosis
3. armacokinetics/”>Ph armacokinetics of Isoniazid
4. Isoniazid – StatPearls
5. Isoniazid Preventive Therapy for the Prevention of Tuberculosis in Adults and Children
6. Antitubercular Agents – StatPearls
7. Current and Future Treatment Regimens for Tuberculosis
8. High-Dose Isoniazid in Tuberculosis Treatment
9. Immunomodulatory Effects of Antibiotics
10. Oxidative Stress in Mycobacterium tuberculosis Infection
11. Isoniazid Toxicity – StatPearls
12. Isoniazid-induced Liver Injury: Current Concepts
13. Treatment Outcomes of Patients with Tuberculosis
14. Factors Influencing Treatment Outcomes in Drug-Susceptible Pulmonary Tuberculosis
15. The Role of Isoniazid Preventive Therapy in Tuberculosis Control
16. Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research
17. New Drugs for the Treatment of Tuberculosis