Rapid Communication - Journal of Clinical Respiratory Medicine (2022) Volume 6, Issue 1

Pathophysiology of isoniazid in treatment of pulmonary tuberculosis

Katie Johnson^*

Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, Netherlands

*Corresponding Author:

Katie Johnson
Department of Global Health
Amsterdam Institute for Global Health and Development
Amsterdam University Medical Centers
Amsterdam
Netherlands
E-mail: johnsnk78@amsterdamumc.nl

Received: 31-Jan-2022, Manuscript No. AAJCRM-22-104; Editor assigned: 02-Feb-2022, PreQC No. AAJCRM-22-104(PQ); Reviewed: 16-Feb-2022, QC No AAJCRM-22-104; Revised: 19-Feb-2022, Manuscript No. AAJCRM-22-104(R); Published: 26-Feb-2022, DOI:10.35841/aajcrm-6.1.104

Citation: Johnson K. Pathophysiology of isoniazid in treatment of pulmonary tuberculosis. J Clin Resp Med. 2022;6(1):104

Introduction

For its powerful early bactericidal action, isoniazid (INH) is an essential first-line anti-TB drug. Resistance to INH, whether alone or in combination with other medications, is currently the most frequent kind of anti-TB drug resistance. INH resistance without concomitant rifampicin (RIF) resistance was found in 7.1% of new TB patients and 7.9% of previously treated TB cases worldwide. In general, "INH-resistant" TB refers to a strain that has been proven in vitro to be resistant to INH and susceptible to RIF, independent of concomitant resistance to other anti-TB medications [1]. Resistance to a single first-line medication, such as INH, and vulnerability to any other anti-TB medicines is referred to as "INH monoresistance" TB39. Resistance to INH is most typically caused by mutations in the katG or inhA genes, although it can also be caused by mutations in other genes, such as the ahpC32 gene. To be effective against tuberculosis, INH must be activated by catalase-peroxidase, an enzyme controlled by katG. INH resistance can be caused by mutations in katG, most often at Ser315Thr.

Drug resistance occurs in Mycobacterium TB as a result of spontaneous genetic changes. As a result, acquired drug resistance is more likely to develop where there is a high bacterial population, such as in the lungs, or when an ineffective treatment combination or dose is provided. Anti- TB medication malabsorption is a rare cause of acquired resistance. There have been reports of risk factors for acquiring INH resistance, and most studies have established a substantial link between a history of TB therapy and INH resistance.

Resistance to additional drugs

Additional drug resistance, particularly to RIF, is a major worry when treating INH-resistant TB with first-line regimens, and it can lead to the establishment of MDR-TB. Drug resistance has been the subject of several studies, particularly among patients who had poor results following treatment for INHresistant TB [2].

Treatment duration

The ATS-CDC-IDSA TB treatment recommendations indicate that antituberculosis medications be dosed according to optimal body weight. This suggestion is based on a single case report, which is alarming considering that weight and/ or height have a major impact on the pharmacokinetics of first-line medications. Rifampin 10 mg/kg (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg), pyrazinamide 15–30 mg/kg (maximum 2 g), and ethambutol 15–20 mg/ kg (maximum 1.6 g) given daily for 8 weeks, followed by isoniazid 15 mg/kg (maximum 900 mg) and rifampin 10 mg/ kg (maximum 600 mg) for 2–3 times/week for 18 weeks.

Because of the increased risk of acquiring rifamycin resistance, individuals with the human immunodeficiency virus (HIV) who have CD4+ lymphocyte counts fewer than 100 cells/mm3 should receive daily (or thrice-weekly) medication in the continuation phase. Patients with cavitary illness who have a positive culture at 2 months should have their therapy prolonged for another 12 weeks (for a total of 9 months). In the treatment of HIV-negative individuals with no cavitary illness and a negative sputum acid-fast bacilli (AFB) smear at 2 months, a once-weekly isoniazid and rifapentine combination can be utilised in the continuation phase for 18 weeks. However, because of the increased risk of relapse and the development of rifamycin monoresistance, rifapentine should not be used to treat HIV-infected individuals [3].

Treatment interruptions

Management interruption is a typical clinical problem in the treatment of drug-susceptible TB. Noncompliance or medication toxicity is the most typical causes of treatment interruptions. Unfortunately, there are no statistics to help doctors manage patients who stop taking their medication. Various solutions based on expert opinion have been established by health administrations

The recommendations indicate estimating the proportion of doses in the continuation phase that have been completed for patients in the continuation phase. If the patient completed at least 80% of the therapy and had a negative first AFB smear, no further treatment may be necessary. For individuals whose initial AFB smear was positive, completion of the continuation phase is still indicated. Patients who completed less than 80% of the continuation phase and had a treatment break of less than 3 months can continue therapy while waiting for the results of the repeat culture. If the repeat culture comes out negative, treatment should be finished within 9 months of the start date. If therapy has not been completed within 9 months of the original start date, it should be restarted from the new start date. If the repeat culture is positive, the patient should resume a four-drug therapy while susceptibility findings are obtained. Four-drug therapy employing directly observed therapy should be continued from the beginning in patients who have had treatment pauses of at least 3 months. AFB smears and cultures should also be rechecked on the patient. After a total of 9 months of therapy, if the repeat culture is negative, treatment can be halted [4].

Conclusion

Tuberculosis is still a major public health concern across the world. Although the first-line therapy for drug-susceptible TB has remained unchanged for decades, breakthroughs are being made in the field, such as the definition of PK-PD indices and targets for antituberculosis medications. Future TB research should aim to reduce the length of treatment and reduce the risk of resistance developing during treatment

References

1. Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368(9547):1575-80.

Indexed at, Cross Ref

2. Kim HR, Hwang SS, Kim HJ, et al. Impact of extensive drug resistance on treatment outcomes in non–HIV-infected patients with multidrug-resistant tuberculosis. Clin Infect Dis. 2007;45(10):1290-95.

Indexed at, Google scholar, Cross Ref

3. Yeager RL, Munroe WG, Dessau FI. Pyrazinamide (aldinamide) in the treatment of pulmonary tuberculosis. Am Rev Tuberc. 1952;65(5):523-46.

Indexed at, Google scholar

4. Mitchison DA. Basic mechanisms of chemotherapy. Chest. 1979;76(6):771-81.

Indexed at, Google scholar, Cross Ref