High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis
High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis
The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB)
 in resource-limited countries is being increasingly recognized. This single center, double
 blind, randomized controlled trial was designed to compare the time required for sputum
 culture conversion and extent of radiological improvement in cases of MDR pulmonary
 tuberculosis when isoniazid was included (both at a regular dose and at a high dose) as an
 adjuvant to the standardized second line of treatment. The study was designed to test the
 hypothesis that inclusion of high-dose isoniazid will enhance the effectiveness of the second
 line of treatment in cases of MDR-TB without significantly increasing the toxicity.
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993.
 The global problem of tuberculosis is further complicated by a substantial increase in drug
 resistant tuberculosis. Available data suggest that drug resistant TB especially multi drug
 resistant may represent a public health threat in areas with a high prevalence of
 tuberculosis, suboptimal TB control programmes and/ or HIV. The cure rate of these cases has
 been reported to be lower than for non-drug resistant TB with a failure rate of 44%. New
 therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s.
 Strains of Mycobacterium Tuberculosis (M. tub.) in H resistant cases often contain mixture of
 susceptible & resistant organisms. Use of high dose H (16- 20 mg/kg) can eliminate
 susceptible & those with low level resistance4. This Study was done to evaluate the role of
 isoniazid (INH) at high & normal dosages as an adjuvant therapy in treatment of patients with
 persistent culture positive pulmonary tuberculosis despite 6 months of continuous first line
 antitubercular treatment and on culture at least resistant to isoniazid and rifampicin.
Inclusion Criteria:

 -  Consecutive patients reporting to the study center

 -  Sputum-positive for acid-fast bacilli

 -  HIV-uninfected

 -  MDR-TB defined as resistance to at least the following two drugs: Isoniazid and
 Rifampicin.

 Exclusion Criteria:

 -  Unwilling to give consent

 -  Abnormal renal or hepatic profile

 -  History suggestive of isoniazid hypersensitivity

 -  Pregnancy

 -  Lactating mother

 -  Previous history of taking any of the following: kanamycin, prothionamide,
 levofloxacin, cycloserine and p-aminosalicylic acid