Quinolones and multidrug-resistant tuberculosis

Abstract

The prevalence of initial resistance of multidrug-resistant tuberculosis (MDR-TB) to at least isoniazid (INH) and rifampicin (RFP) in Thailand during the period 1993-1997 is reported; in this era, trends for INH + RFP + streptomycin (SM) and ethambutol (EMB), INH + RFP + SM or EMB and MDR-TB were stable. The prevalence of acquired MDR-TB is on a slight downward trend, with the latest level at 22.6%. Recommended management of MDR-TB is outlined and advantages and disadvantages of these guidelines discussed. The role of ofloxacin in MDR-TB is presented, with results from a study performed by the Thailand CDC showing that the percentage of strains resistant to ofloxacin was 4.3%, and to ciprofloxacin was 8.3%. The resistance to both ofloxacin and ciprofloxacin was very low at 1.4%. The percentage of cross-resistance between these fluoroquinolones was also low; 33% resistant to ofloxacin were also resistant to ciprofloxacin and only 17% of those resistant to ciprofloxacin were also resistant to ofloxacin. Results from a clinical trial evaluating ofloxacin with other drugs for MDR-TB are also reported. The regimen comprised ofloxacin 600 mg/day, pyrazinamide (PZA), two to three months of kanamycin (KM) or amikacin (AMK), para-aminosalicylic acid (PAS) plus EMB or thiacetazone. Drugs were given for 18 months. Follow-up was every three months for two years. Preliminary results revealed that the percentage of acquired MDR-TB resistant to specific agents was as follows: 36% resistant to INH and RFP, 23% resistant to INH, RFP plus EMB, 27% resistant to INH, RFP and SM, and 14% resistant to all four of these agents (INH + RFP + SM + EMB). All isolates were sensitive to ofloxacin. At one month of treatment, sputum culture conversion was approximately 25%, climbing to 93% by nine months of treatment. Treatment with ofloxacin in a combined regimen achieved a success rate of 78%. The role of quinolones in preventing TB in MDR-TB contacts is also discussed.