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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.

Setting: An urban tuberculosis control program where an enhanced multidrug-resistant tuberculosis (MDR-TB) management plan coordinated care with multiple providers., Objective: To evaluate treatment outcomes of primary MDR-TB patients treated by multiple providers., Design: Retrospective cohort study of tuberculosis patients from 1992-1997 provided that 1) their Mycobacterium tuberculosis isolates were resistant to at least isoniazid and rifampin, and 2) they had had < or = 30 days of anti-tuberculosis treatment prior to the collection of the first MDR-TB specimen., Results: More than 100 facilities and providers reported 856 MDR-TB patients. Treatment completion reached 70% among non-HIV-infected and 30% among HIV-infected persons; 57.2% of the cohort died prior to treatment completion, 26.5% completed treatment, 16.0% transferred out, refused treatment or were lost to follow-up and 0.2% are still in care. Diagnosis in the later years of the study or cavitation on chest radiograph was independently associated with increased completion among HIV-infected patients. Eight of the 227 (3.5%) patients who completed treatment relapsed (relapse rate 1.01/100 person-years), two with drug-susceptible strains., Conclusion: A comprehensive MDR-TB control program improved the outcomes of both HIV-infected and non-infected individuals, despite management by multiple providers. Relapse was infrequent among patients who completed the recommended regimens.

Background: Nosocomial tuberculosis (TB) transmission has decreased dramatically in New York State since 1992; however, health care workers (HCWs) still compose >3% of TB cases., Methods: Aggregate surveillance data on incident TB cases from 1994 to 2002 were examined for trends among HCWs. Additional information was available for HCW cases from 1998 to 2002, including facility type, tuberculin skin test (TST) result at hire, and treatment of latent TB infection (TLTBI)., Results: In New York State, 2.5% of TB cases in 1994 and 4.0% in 2002 were in HCWs (P value for trend <.001). Fifty percent of HCWs TB cases in 1994 and 77.6% in 2002 were in non-US born (P = .002) HCWs. Multidrug-resistant TB in HCWs decreased from 15.6% in 1994 to 6.9% in 2002 (P = .001). Of 297 HCWs TB cases in 1998-2002, 54.9% were TST positive at hire, and 21.2% had unknown TST result; 50.2% of 221 HCWs who were TST positive at or after hire met guidelines for TLTBI, and 23.4% received treatment. The highest proportion with unknown TST at hire and the lowest proportion receiving TLTBI were in ambulatory facilities., Conclusion: Many HCWs who developed TB were either TST positive at hire and did not receive TLTBI or did not receive TST at hire. Facilities should encourage treatment for HCWs who meet criteria for TLTBI. Provider education should focus on ambulatory facilities.

Setting: New York City (NYC)., Objectives: To examine the extent to which prior tuberculosis (TB) treatment, length of residence in the United States and other factors are associated with the occurrence of drug resistance among non-US-born persons in NYC., Design: Cases were non-US-born persons diagnosed with TB in NYC from 1998-1999 and from 2001-2002, with an initial Mycobacterium tuberculosis isolate resistant to any first-line anti-tuberculosis drug. Controls were randomly selected from non-US-born persons whose isolates were susceptible to all first-line anti-tuberculosis drugs., Results: Overall, cases with multidrug-resistant (MDR) TB were more likely to have had prior TB treatment; other drug resistance was not associated with prior TB treatment. In a multivariate model, the relationship between MDR-TB and prior treatment remained significant for non-US-born persons regardless of length of time in the U.S., Conclusions: The findings underscore the utility of monitoring trends in drug resistance among the non-US-born by time in the US and prior treatment to determine where or when drug resistance may be occurring.

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.

One multidrug-resistant Mycobacterium tuberculosis (MDRTB) strain, strain W, caused several nosocomial outbreaks in New York City (NYC) during 1 January 1990-31 July 1993. We reviewed all MDRTB cases verified during 1 August 1993-31 December 1999 that had isolates with either this DNA pattern or a variant of this strain, and we compared them to the outbreak cases. Of 427 DNA-confirmed cases from 1990-1999, 161 (37%) were from 1 August 1993-31 December 1999; these 161 cases, from 56 hospitals and 2 correctional sites, constituted 28% of all MDRTB cases in NYC during this period. Compared with those from 1 January 1990-31 July 1993, patients from 1 August 1993-31 December 1999 were less likely to be infected with human immunodeficiency virus, to have been born in the United States, to be homeless, to have been incarcerated, and to have epidemiological links; 16% of patients had nosocomial- and 9% had community-exposure links. This strain was disseminated widely in the community during the outbreaks; postoutbreak cases likely represent reactivated disease among individuals infected during the outbreak periods in the community.