Sonal S. Munsiff

Emergence of vancomycin-resistant enterococci in New York City

Enterococci, a common cause of nosocomial infection, are intrinsically resistant to most antimicrobials and readily acquire additional resistance. Vancomycin-resistant enterococci (VRE) have caused clusters of nosocomial infections since 1988. In April, 1991, the New York City Department of Health asked all city laboratories to submit suspected VRE isolates for confirmation. Clinical and epidemiological characteristics of the first 100 patients with VRE were identified, and antimicrobial susceptibility testing, restriction enzyme analysis, and DNA-DNA hybridisation with the vanA gene probe were done. From September, 1989, to October, 1991, 361 patients with VRE were identified at 38 hospitals. The number of hospitals reporting VRE increased from 1 in 1989 to 38 by October, 1991. 98% of 100 VRE infections were nosocomially acquired and 83% patients had received vancomycin and/or a cephalosporin in the 30 days before isolation of VRE. Of 23 isolates from 21 of the first 100 patients, 19 (83%) were resistant to all available antimicrobials. Four vanA probing patterns were noted, and restriction enzyme analysis of the 23 isolates revealed 14 strains. VRE have emerged rapidly in New York City. Molecular analyses suggest that a highly mobile genetic element--eg, a transposon--is responsible for the rapid spread of vancomycin resistance.

Relapse and Acquired Rifampin Resistance in HIV-Infected Patients with Tuberculosis Treated with Rifampin- or Rifabutin-Based Regimens in New York City, 1997–2000

BACKGROUND The relationship between rifamycin use and either relapse or treatment failure with acquired rifampin resistance (ARR) among human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) is not well understood. METHODS We conducted a retrospective cohort study of HIV-infected and HIV-uninfected persons with rifampin-susceptible TB, (1) to compare relapse rates, ARR, and treatment failure, according to HIV serostatus; and (2) to examine whether and how use of rifamycin was associated with clinical outcomes of interest among HIV-infected patients with TB. RESULTS HIV-infected patients were more likely to have ARR than were HIV-uninfected patients (0.9% vs. 0.1%; P = .007), and the association remained significant in multivariate analysis (adjusted odds ratio [OR], 5.5; 95% confidence interval [CI], 1.4-21.5). Among HIV-infected patients with TB, none of 57 patients treated with rifabutin-based regimens alone had ARR, and only 1 of 395 patients treated with rifabutin given in combination with a rifampin-based regimen had ARR, whereas 6 of 355 patients treated with a rifampin-based regimen alone had relapse and ARR. HIV-infected patients treated with rifampin-based regimens alone had a higher risk for relapse and development of rifampin resistance if intermittent dosing of rifampin was started during the intensive phase of treatment, compared with patients who did not receive intermittent dosing (hazard ratio [HR] for relapse, 6.7 [95% CI, 1.1-40.1]; HR for ARR, 6.4 [95% CI, 1.1-38.4]). This association remained when confined to patients with a CD4+ T lymphocyte count of < 100 lymphocytes/mm3. Intermittent dosing started only after the intensive phase of treatment did not increase the risks of relapse and ARR among HIV-infected patients with TB. CONCLUSION The risk for ARR among HIV-infected persons with TB did not depend on the rifamycin used but, rather, on the rifampin dosing schedule in the intensive phase of treatment.

Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000–06

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.

Persistence of a Highly Resistant Strain of Tuberculosis in New York City during 1990–1999

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.

Adherence to treatment of latent tuberculosis infection in a clinical population in New York City.

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.

Performance of Nucleic Acid Amplification Tests for Diagnosis of Tuberculosis in a Large Urban Setting

BACKGROUND A diagnosis of tuberculosis (TB) relies on acid-fast bacilli (AFB) smear and culture results. Two rapid tests that use nucleic acid amplification (NAA) have been approved by the US Food and Drug Administration for the diagnosis of TB based on detection of Mycobacterium tuberculosis from specimens obtained from the respiratory tract. We evaluated the performance of NAA testing under field conditions in a large urban setting with moderate TB prevalence. METHODS The medical records of patients with suspected TB during 2000-2004 were reviewed. Analysis was restricted to the performance of NAA on specimens collected within 7 days after the initiation of treatment for TB. The assays sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. RESULTS The proportion of patients with confirmed or suspected TB whose respiratory tract specimens were tested by use of NAA increased from 429 (12.9%) of 3334 patients in 2000 to 527 (15.6%) of 3386 patients in 2004; NAA testing among patients whose respiratory tract specimens tested positive for AFB increased from 415 (43.6%) of 952 patients in 2000 to 487 (55.5%) of 877 patients in 2004 (P < .001 for both trends). Of the 16,511 patients being evaluated for pulmonary TB, 4642 (28.1%) had specimens that tested positive for AFB on smear. Of those 4642 patients, 2241 (48.3%) had NAA performed on their specimens. Of those 2241 patients, 1279 (57.1%) had positive test results. Of those 1279 patients, 1262 (98.7%) were confirmed to have TB. For 1861 (40.1%) of the 4642 patients whose specimens tested positive for AFB on smear, the NAA test had a sensitivity of 96.0%, a specificity of 95.3%, a PPV of 98.0%, and an NPV of 90.9%. For 158 patients whose specimens tested negative for AFB on smear, the NAA test had a sensitivity of 79.3%, a specificity of 80.3%, a PPV of 83.1%, and an NPV of 76.0%, respectively. For the 215 specimens that tested positive for AFB by smear, we found a sensitivity, specificity, PPV, and NPV of 97.5%, 93.6%, 95.1%, and 96.8%, respectively. A high-grade smear was associated with a better test performance. CONCLUSION NAA testing was helpful for determining whether patients whose specimens tested positive for AFB on smear had TB or not. This conclusion supports the use of this test for early diagnosis of pulmonary and extrapulmonary TB.

Rifampin-monoresistant tuberculosis in New York City, 1993-1994.

All New York City patients whose cultures yielded Mycobacterium tuberculosis with isolated resistance to rifampin in 1993 and 1994 were included in this study. Of the 96 patients, 48 (50%) had primary resistance, 32 (33%) had acquired resistance, and 16 (17%) had unclassified resistance; 66% had histories of illicit drug use, and 79% were infected with human immunodeficiency virus (HIV). The median time to emergence of resistance was 40 weeks among the 32 patients with acquired resistance. Each of the HIV-infected patients with acquired resistance (cases, n = 29) was matched to two HIV-infected patients who had disease due to fully susceptible M. tuberculosis (controls, n = 58). In multivariate analysis, factors associated with the emergence of rifampin resistance were as follows: a sputum smear positive for acid-fast bacilli, advanced immunosuppression, and nonadherence to therapy.

Universal Genotyping in Tuberculosis Control Program, New York City, 2001–2003

Real-time universal genotyping decreased unnecessary treatment.

Molecular Epidemiology of Multidrug-Resistant Tuberculosis, New York City, 1995–1997

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 >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 1990s when MDRTB outbreaks and tuberculosis transmission were widespread in New York.

Rifapentine for the Treatment of Pulmonary Tuberculosis

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.