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In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003-2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.

Objective: To review outcomes of human immunodeficiency virus (HIV) positive tuberculosis (TB) patients in New York City (NYC) to determine if the World Health Organization treatment success target of 85% was met in a setting with ready access to treatment for HIV and TB., Design: Retrospective review of new TB patients diagnosed from 1995 to 2004, excluding patients with rifampin (RMP) resistance., Results: Of 9198 eligible TB patients, 83% had achieved treatment success, 8% died during treatment, 4% failed, 3% defaulted and 2% were transferred from NYC. Among 6374 HIV-negative individuals, treatment success was consistently over 85%; 5% died during treatment. Among 2824 HIV-positive individuals, treatment success was 72% overall and 66% in sputum acid-fast bacilli smear-positive patients. Mortality among the HIV-positive decreased from 26% in 1995 to 14% in 2004. HIV-positive patients achieved higher treatment success if 1) they received treatment by directly observed therapy (DOT) (82% vs. 74%, OR(adj) = 1.80, 95%CI 1.44-2.26), or 2) were administered rifabutin (RFB) in the regimen, a proxy for receiving antiretroviral therapy (ART) (84% vs. 78%, OR(adj) = 1.49, 95%CI 1.20-1.85). Treatment success of 85% was achieved in HIV-positive patients who received RFB and DOT., Conclusion: High mortality precluded achieving 85% treatment success among HIV-positive TB patients. DOT and ART remain essential for improving success among co-infected patients everywhere.

Background: Low adherence to treatment of latent tuberculosis infection (TLTBI) diminishes TB prevention efforts. This study examined the treatment completion rate among those who started TLTBI and factors associated with adherence to TLTBI., Methods: Patients who started TLTBI in New York City (NYC) Health Department chest clinics during January 2002-August 2004 were studied. TLTBI completion rate were described and compared according to patient demographic and clinical characteristics by regimen using univariate analysis and log-binomial regression., Results: A total of 15 035 patients started and 6788 (45.2%) completed TLTBI. Treatment completers were more likely than non-completers to be >or=35 years old (52.5%, adjusted relative risk (aRR)=1.2, 95% confidence interval (CI)=1.1, 1.2), contacts to pulmonary TB patients (57.4%, aRR=1.5, 95% CI=1.4, 1.7), treated by directly observed preventive therapy (DOPT) (71.4%, aRR=1.3, 95% CI=1.2, 1.3), and to have received the rifamycin-based regimen (60.0%, aRR=1.2, 95% CI=1.1, 1.3). The completion rate with an isoniazid regimen did not differ between HIV-infected and HIV-uninfected persons. Among those who failed to complete, 3748 (47.8%) failed to return for isoniazid and 59 (14.7%) for rifamycin after the first month of medication dispensing., Conclusions: Shorter regimen and DOPT increased completion rates for LTBI. Though efforts to improve TLTBI completion need to address all groups, greater focus is needed for persons who are contacts and HIV-infected, as they have higher risk of developing TB.

Unlabelled: Rationale Linezolid may be effective for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious adverse events are common and there is little information on the management of these toxicities., Methods: We retrospectively reviewed public health and medical records of 16 MDR TB patients, including 10 patients with XDR TB, who were treated with linezolid in New York City between January 2000 and December 2006, to determine treatment outcomes and describe the incidence, management and predictors of adverse events., Results: Linezolid was added to MDR TB regimens for a median duration of 16 months (range: 1-29). Eleven patients (69%) completed treatment, four (25%) died and one (6%) discontinued treatment without relapse. Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11) after starting linezolid, gastrointestinal adverse events occurred in 13 (81%) patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events were managed by combinations of temporary suspension of linezolid, linezolid dose reduction and symptom management. Five (31%) patients required eventual discontinuation of linezolid. Myelosuppression was more responsive to clinical management strategies than was neurotoxicity. Leucopenia and neuropathy occurred more often in males and older age was associated with thrombocytopenia (P < 0.05)., Conclusions: The majority of MDR TB patients on linezolid had favourable treatment outcomes, although treatment was complicated by adverse events that required extensive clinical management.

Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.

Rationale: Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans., Objective: To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens., Methods: Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed., Measurements: The primary endpoint was sputum culture status at 2 mo of treatment., Results: Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy., Conclusions: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.

Background: Two drug-resistance surveys showed a very high prevalence of drug resistance among isolates obtained from patients with tuberculosis in 1991 and 1994 in New York, New York., Methods: A cross-sectional survey in April 1997 and a survey of incident cases in April-June 2003 were conducted. The trend in the proportion of drug resistance in the 4 surveys was examined separately for prevalent and incident cases. Risk factors for drug resistance in incident cases were also assessed., Results: The number of patients was 251 in the 1997 survey and 217 in the 2003 survey. Among prevalent cases, the percentage of cases with resistance to any antituberculosis drug decreased from 33.5% in 1991 to 23.8% in 1994 and to 21.5% in 1997 (P < .001, by test for trend); cases of multidrug-resistant tuberculosis also decreased significantly, from 19% in 1991 to 6.8% in 1997 (P < .001, by test for trend). Among incident cases in the 4 surveys, the decrease in resistance to any antituberculosis drugs was not statistically significant; however, the decrease in multidrug-resistant tuberculosis (from 9% in 1991 to 2.8% in 2003) was statistically significant (P = .002, by test for trend). However, in 2003, a worrisome increase in incident cases of multidrug-resistant tuberculosis (an increase of 23%) was seen among previously treated patients with pulmonary tuberculosis not born in the United States. Human immunodeficiency virus infection, a strong predictor for drug resistance in 1991 and 1994, was not associated with drug resistance in subsequent surveys., Conclusions: Intensive case management, including directly observed therapy, adherence monitoring, and periodic medical review to ensure appropriate treatment for each patient, should be sustained to prevent acquired drug resistance.

Objective: The purpose of this study was to evaluate whether non-US-born pregnant women receiving prenatal care are targeted for treatment of latent tuberculosis (TB) infection (LTBI) with isoniazid (INH) to prevent active TB., Study Design: This was a retrospective chart review study of 730 non-US-born pregnant women receiving care at 5 New York City prenatal clinics from 1999 to 2000., Results: Among 678 women with known tuberculin skin test (TST) status, 341 (50.3%) had a TST-positive result, including 200 who were newly diagnosed. Of 291 TST-positive women with no previous LTBI treatment or history of TB, 27 (9.3%) completed > or =6 months of INH. In a subset with detailed follow-up, the most important reasons for not completing treatment were nonreferral for evaluation of a TST-positive result (30.9%), not keeping the appointment (17.9%), and nonadherence with prescribed treatment (34.6%)., Conclusion: The prenatal setting represents a missed opportunity to link TST-positive non-US-born women with LTBI treatment and support for treatment completion.

Setting: Large urban tuberculosis control program., Objectives: To determine the frequency and characteristics of treatment interruptions, and the factors associated with the different types of treatment interruptions., Design: This was a case-control study using culture-positive tuberculosis (TB) patients verified in 1998-1999. Case patients included those in whom any of the following mutually exclusive categories of treatment interruption: default with return to therapy, directly observed therapy nonadherence, default without return to therapy, or multiple types of interruptions. Controls were selected randomly from the cohort., Results: Overall, 6.0 percent of patients had treatment interruptions. All types of treatment interruption were associated with prolonged treatment course and decreased treatment completion rates. The median number of months to treatment interruption was 4.0 (range, 0.5-28.9 months). Two factors were significantly associated with every type of interruption: homelessness and lack of awareness of the severity of TB disease. In multivariate analysis, only lack of awareness of the severity of disease remained independently associated with all interruption types., Conclusion: Efforts to improve patients' understanding of TB disease and related treatment issues may be an important TB control program strategy and should be emphasized at the initiation of therapy and at intervals throughout the treatment course to minimize treatment interruption.

Study Objectives: Therapeutic drug monitoring (TDM) is the process of obtaining the serum concentration of a medication and modifying the dose based on the results. Little is known about the application of TDM in the treatment of patients with multidrug-resistant (MDR) tuberculosis (TB) in clinical practice. This study characterized how TDM was applied in the management of MDR TB patients, and examined the clinical indications for ordering TDM, the process for obtaining drug concentrations, and the clinician response to the drug concentrations., Design: In a retrospective study, we compared the clinical and demographic characteristics of MDR TB patients who received TDM with those who did not. The clinical application of TDM also was described in patients who received TDM., Setting: A municipal TB control program., Patients or Participants: Patients in whom TB was diagnosed that was caused by an isolate resistant to at least isoniazid and rifampin, and who received treatment for TB in one of the health department chest clinics between July 1, 1993, and August 31, 1997, were studied., Results: Forty-nine patients receiving TDM had a longer time to culture conversion and treatment duration, more pulmonary TB in combination with an extrapulmonary site, drug resistance, and visits to the health department clinics (p < 0.05) than the 60 patients without TDM. Of the 49 patients who had initial TDM, 73.5% of them had the reason for being tested specified. A total of 85.7% of initial TDM results were collected at the appropriate time of blood sampling. Clinician response to TDM results varied with the drug that was being tested., Conclusions: The use of TDM depended largely on the patient's clinical presentation. Site-specific guidelines on the use of TDM for managing TB patients may maximize the benefit of TDM.

Injection drug users (IDUs) were heavily affected by the tuberculosis (TB) resurgence in New York City in the 1990s. We assessed the effectiveness of screening for latent TB infection in methadone users and of selective treatment with isoniazid. Risk for future TB was classified as low or high on the basis of tuberculin, anergy, and HIV test results. The cohort of 2212 IDUs was followed up for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional hazards model of high-risk IDUs, the risk of TB was associated with HIV infection (HR 10.3; 95% CI, 3.4-31.3); receipt of <6 months of isoniazid therapy (HR 7.6; 95% CI, 1.02-57.1); a CD4+ T lymphocyte count of <200 cells/mm3 (HR 6.6; 95% CI, 1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs.

From January 1, 1995, to December 31, 1997, we reviewed records of all New York City patients who had multidrug-resistant tuberculosis (MDRTB); we performed insertion sequence (IS) 6110-based DNA genotyping on the isolates. Secondary genotyping was performed for low IS6110 copy band strains. Patients with identical DNA pattern strains were considered clustered. From 1995 through 1997, MDRTB was diagnosed in 241 patients; 217 (90%) had no prior treatment history, and 166 (68.9%) were born in the United States or Puerto Rico. Compared with non-MDRTB patients, MDRTB patients were more likely to be born in the United States, have HIV infection, and work in health care. Genotyping results were available for 234 patients; 153 (65.4%) were clustered, 126 (82.3%) of them in eight clusters of >or=4 patients. Epidemiologic links were identified for 30 (12.8%) patients; most had been exposed to patients diagnosed before the study period. These strains were likely transmitted in the early 1990 s when MDRTB outbreaks and tuberculosis transmission were widespread in New York.

Setting: New York City., Objective: To evaluate the yield of continued monthly sputum monitoring after culture conversion., Design: A retrospective review of tuberculosis patients verified between 1 January 1995 and 31 December 1996 who had: 1) pulmonary tuberculosis with organisms susceptible to isoniazid and rifampin; 2) culture conversion; and 3) completed therapy. We assessed time to smear and culture conversion and number of persons who developed a positive culture after culture conversion (culture reversion)., Results: Of 1440 patients, 379 were cared for by tuberculosis control program providers and 1061 were cared for by other providers; 813 (56%) were initially smear-positive. After the fifth month, 44 (5.3%) were smear-positive; four of these were culture-positive. Eighteen (1.3%) had culture reversions; eight were smear-positive. Excluding one specimen per patient collected at treatment completion, 7967 sputum samples were collected after culture conversion. The minimum estimated cost per culture reversion detected was $26,557., Conclusion: Continued monthly monitoring of sputum after culture conversion identified a very small number of patients who had culture reversion. However, patients who cannot tolerate or adhere to a standard regimen may need continued monitoring to assess response to treatment. For all patients a specimen should be collected at the end of treatment to document cure.

The optimal duration of tuberculosis treatment for persons infected with human immunodeficiency virus (HIV) has been debated. A cohort of 4571 culture-positive drug-susceptible patients who received > or =24 weeks of standard 4-drug tuberculosis treatment were assessed to determine the incidence of tuberculosis relapse. Tuberculosis "recurrence" was defined as having a positive culture < 30 days after the last treatment date and "relapse" as having a positive culture > or =30 days after the last treatment. Patients infected with HIV were more likely than those who were uninfected to have recurrence or relapse (2.0 vs. 0.4 per 100 person-years, P< .001). Patients infected with HIV who received < or =36 weeks of treatment were more likely than those who received > 36 weeks to have a recurrence (7.9% vs. 1.4%, P< .001). Clinicians should be aware of the possibility of recurrence of tuberculosis 6-9 months after the start of treatment. Sputum evaluation to ensure cure or assessment 3 months after completion of treatment should be performed among persons infected with HIV who receive the shorter regimen.

A distinct branch of the Mycobacterium tuberculosis W phylogenetic lineage (W14 group) has been identified and characterized by various genotyping techniques. The W14 group comprises three strain variants: W14, W23, and W26, which accounted for 26 clinical isolates from the New York City metropolitan area. The W14 group shares a unique IS6110 hybridizing banding motif as well as distinct polymorphic GC-rich repetitive sequence and variable number tandem repeat patterns. All W14 group members have high levels of streptomycin resistance. When the streptomycin resistance rpsL target gene was sequenced, all members of this strain family had an identical mutation in codon 43. Patients infected with the W14 group were primarily of non- Hispanic black origin (77%); all were US-born. Including HIV positivity, 84% of the patients had at least one known risk factor for tuberculosis.