Treatment Duration for Patients with Drug-Resistant Tuberculosis, United States

To the Editor: In the United States, almost 80% of tuberculosis (TB) cases are diagnosed on the basis of positive culture results for Mycobacterium tuberculosis, and >90% of initial isolates are tested for drug susceptibilities (1,2). Recommended treatment durations are 6–9 months for patients with isoniazidand rifampin-susceptible TB; <18 months for patients with rifampinmonoresistant TB; and, following culture conversion, 18–24 months for patients with isoniazidand rifampinresistant TB (3). Appropriately completed TB treatment maximizes patient and public health benefi ts and minimizes adverse events and costs (3). We examined treatment duration by drug resistance pattern among a national cohort of case-patients with TB diagnosed in the United States. We analyzed routinely collected data from the Centers for Disease Control and Prevention’s National TB Surveillance System. To ensure that all patients had at least 3 years of follow-up, we examined cases of culture-positive TB verifi ed in 2006. We calculated treatment duration for patients who were alive and had initiated TB therapy at diagnosis and who had results for initial drug susceptibility testing. Treatment duration was calculated by subtracting the therapy start date from the therapy end date. The 15th day of the month was assigned as the day treatment started or ended if that information was missing. Patients who did not complete therapy were censored as of the last known follow-up. We categorized cases as isoniazid monoresistant; rifampin monoresistant; multidrug resistant (MDR), defi ned as resistant to at least isoniazid and rifampin; or drug susceptible, defi ned as susceptible to isoniazid, rifampin, and ethambutol and with no known resistance to pyrazinamide (i.e., pyrazinamide susceptible or missing test results). Survival distributions by drug-resistance pattern were estimated by using Kaplan-Meier analysis and compared by using log-rank test statistics. Patient characteristics were compared by using χ2 tests or, when cell sizes were <5, Fisher exact tests. Of 13,734 TB cases reported in 2006, 10,747 (78.3%) were confi rmed by culture. Of the 10,747 patients with culture-confi rmed TB, 10,120 (94.2%) were alive and had initiated TB therapy at diagnosis and had start and end therapy dates and initial drug susceptibility results. Duration of treatment was calculated for 9,734 (96.2%) cases, of which, 8,973 (92.2%) were classifi ed as drug-susceptible, 618 (6.3%) as isoniazid-monoresistant, 24 (0.2%) as rifampin-monoresistant, and 119 (1.2%) as MDR TB. The remaining 386 (3.8%) cases were excluded from analysis because the patients had pyrazinamide-monoresistant TB, suggestive of Mycobacterium bovis infection (165), or they were missing susceptibility testing results for isoniazid, rifampin, or ethambutol (112) or had other resistance patterns (109). At 12 months, the cumulative completion of therapy among patients with drug-susceptible, isoniazid-monoresistant, rifampinmonoresistant, or MDR TB was 87.6%, 81.0%, 17.4%, and 1.9%, respectively (Figure). At 24 months, 73.9% of patients with rifampinmonoresistant TB and 40.2% with MDR TB had completed treatment. Treatment duration was shortest for patients with drug-susceptible TB (median 252 days), compared with a median of 274, 555, and 766 days for patients with isoniazid-monoresistant, rifampin-monoresistant, and MDR TB, respectively. Differences in treatment duration based on drug susceptibility were signifi cant (p<0.001) for all comparisons. The MDR TB group included 4 extensively drug-resistant cases (also resistant to any fl uoroquinolone and >1 of the injectable drugs capreomycin,