Treatment of multidrug-resistant tuberculosis in Thailand

Abstract

Tuberculosis (TB) has remained the 5th leading cause of death in Thailand for several years. There has been a slight change in the total number of TB cases notified since 1985 when the first case of HIV infection was reported. Although there is an increase in the incidence of TB in HIV-infected cases, the percentage of multidrug-resistant tuberculosis (MDR-TB) in this group is the same as in the HIV-negative group (2.7%). The percentages of total initial drug resistance, four-drug resistance and MDR-TB have increased to 22.4, 1.4 and 4.8%, respectively. Comparable figures for acquired resistance are up to 2.5-, 10- and 6-fold, respectively. The rapid diagnosis and susceptibility pattern of MDR-TB are essential for improving therapeutic outcome. At present there is no defined standard regimen for MDR-TB and clinical practice has been to select a regimen of three to four sensitive or not previously exposed anti-TB drugs. Duration of treatment for 24-30 months depends on severity, previous therapy and the number of drug resistances. Surgery is suggested for persistent positive cases with localized lesions and a good cardiopulmonary reserve. The quinolone, ofloxacin, is a promising drug for MDR-TB, achieving a sputum conversion rate of 59-79%. A prospective study showed a success rate of 67% with no adverse effects. The current Bangkok multicenter trials on ofloxacin 600 mg daily combined with pyrazinamide, p-aminosalicylate, amikacin and ethambutol are ongoing. Good organization of ambulatory TB management combined with directly observed therapy will probably help to reduce the incidence of MDR-TB.

PIP: There has been a slight change in the total number of TB cases notified since 1985, when the first case of HIV was reported. Although there has been an increase in the incidence of TB in HIV-infected cases, the percentage of multidrug-resistant tuberculosis (MDRTB) in this group is the same as in the HIV-negative group (2.7%). The multidrug-resistant (MDR) rate in 1988 was nearly 2% in Thailand, increasing to 5% in 1994. The factors that promote MDRTB in Thailand include irregular drug taking, high initial drug resistance, the prescription of inappropriate regimens, and drug intolerance. The percentages of total initial drug resistance, four-drug resistance, and MDRTB have increased to 22.4%, 1.4%, and 4.8%, respectively. Comparable figures for acquired resistance are up to 2.5-, 10-, and 6-fold, respectively. Duration of treatment for 24-30 months depends on severity, previous therapy, and the number of drug resistances. Surgery is suggested for persistent positive case with localized lesions and good cardiopulmonary reserve. Quinolones are among the most promising drugs for second-line therapy against MDRTB. Quinolone and ofloxacin are promising drugs for MDRTB, achieving a sputum conversion rate of 59-79%. A prospective study showed a success rate of 67% with no adverse effects. However, when different regimens were examined, it was found that at least four anti-TB drugs are required. In current multicenter, controlled, prospective trials in Bangkok, 600 mg ofloxacin daily is combined with pyrazinamide, p-aminosalicylate, amikacin, and ethambutol, with a treatment duration of 18-24 months with a 2-year follow-up. No adverse effects were reported for the ofloxacin 300 mg/day regimen in several studies done. Optimal MDRTB treatment requires appropriate organization for planning and implementation and directly observed therapy. Guidelines developed in April 1996 call for at least 3-4 culture-sensitive drugs given for either 2-2.5 years or until negative sputum cultures have been present for at least 1 year.