Search

Background We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1–2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. Methods This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18–59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. Findings Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744–2746) for the low-dose group, 2269 (1792–2873) for the medium-dose group, and 2895 (2294–3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85–135) in the low-dose group, 110 (87–140) in the medium-dose group, and 141 (111–179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836–11 815) in the low-dose group, 2338 (593–9226) in the medium-dose group, and 7069 (1361–36 725) in the high-dose group. Interpretation Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. Funding Sanofi Pasteur and Biomedical Advanced Research and Development Authority.

SummaryBackgroundThis study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM.MethodsThis Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18–59/≥60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5μg, 10μg or 15μg of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (NAbs) against the D614G variant are presented (primary objectives).FindingsOf 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received ≥1 injections (5μg, n=240; 10μg, n=239; 15μg, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 naïve participants at D36, 96·9%, 97.0% and 97·6% of participants had ≥4-fold-rise in NAb titres from baseline in the 5μg-, 10μg- and 15μg-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5μg-, 10μg- and 15μg-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naïve adults after one injection were higher than titres after two injections in naïve adults.InterpretationTwo injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naïve and non-naïve adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.

Background Management of patients needing OPAT is complex, and requires a multidisciplinary team for transitioning patients from inpatient to outpatient care, ongoing monitoring of labs, antibiotic levels, managing complications of the drugs and intravenous access, and communicating with patients, family, home infusion pharmacies, home care nursing agencies, and the patients’ physicians and other providers. In addition, documentation of each of these activities in the EMR is necessary. Guidance on how to determine number of staff needed for an OPAT program is lacking. Methods We created a detailed step by step list of the various activities done by our OPAT nurse (RN) and determined the time needed to perform each activity. We calculated how many hours of nursing time would be needed per week to perform all the activities for patient care based on our OPAT volume. Results In 2019 we enrolled 767 patients in 835 episodes of OPAT. Our weekly census averages about 120–135 patients. Median duration on OPAT was 30 days. We calculated that our OPAT RN workload was an average of 47.5 hours/week (range of 40–55 hours/week), with time per activity ranging from 5 minutes to 3 hours (table). As this calculated to more than one full time RN position, additional staff were requested. Assessment of Staffing Requirements for an OPAT Program Conclusion We have assessed the workload for OPAT RN(s) in our program based on our 2019 patient volume. We recommend that one RN can safely manage about 500–550 patients per year. Based on this analysis we were successfully able to justify the need for a second RN for our program. Any OPAT Program can do such analysis to determine their OPAT staffing needs, and also plan for the anticipated increases in OPAT volume because of increasing longevity of the population, increase in diabetes incidence, invasive procedures such as arthroplasties, cardiac devices, etc. Limitations This analysis does not include time spent by inpatient staff to arrange for home care and home infusion services. It also does not account for an ID pharmacist time, or the physicians and APP time for management of these patients outside of the billable visit. Disclosures All Authors: No reported disclosures

Background Broad-spectrum antibiotics are often chosen for OPAT due to the convenience of once daily dosing. Current literature suggests that at least 20–30% of these regimens could be narrowed, but this has not been well-defined. Methods This was a multicenter, retrospective cohort study of adult inpatients evaluated by the infectious diseases (ID) team with culture positive infections with susceptibilities (C&S) on select intravenous (IV) antibiotics (ampicillin, ampicillin-sulbactam, cefazolin, ceftriaxone, daptomycin, ertapenem, meropenem, nafcillin, penicillin, piperacillin-tazobactam, and vancomycin) enrolled in OPAT and discharged from January 1 - June 30, 2019. Susceptibilities were not required for Actinomyces, Streptococcus spp., Haemophilus spp., anaerobes, Corynebacterium spp., or coagulase-negative Staphylococcus spp. when considered a contaminant by ID. Patients were excluded if the regimen included oral antibiotics (not including rifampin or metronidazole). Primary outcome was the percent of broad-spectrum regimens that could’ve been narrowed based on C&S (alternative available therapy or AAT group). Secondary outcomes included comparison of baseline characteristics and 30-day readmission rates between patients on narrow-spectrum IV antibiotics (NSA) vs AAT group, and the documented reason(s) for broad-spectrum antibiotic selection. Results 113 patients met study criteria; majority were male (56%), and median age was 60 years. Sixty-four patients were discharged on a broad-spectrum regimen, and 32 (50%) met our AAT definition. Ceftriaxone was used in 75% of these cases (24/32), and mono-microbial Streptococcus spp. infection was the primary indication (54%). AAT group patients were more likely to have Enterobacterales (24.1% vs 1.9% p=< 0.001) or polymicrobial infections (28.1% vs 8.2% p=0.019) compared to NSA group. Reasons for broad-spectrum antibiotic selection were largely undocumented (71%). No significant differences were seen in 30-day readmission rates. Conclusion At our institution, 50% of select IV broad-spectrum OPAT regimens had the potential to be narrowed based on C&S data. This rate is higher than previously reported. It warrants further investigation into the barriers to narrower-spectrum antibiotic prescribing in OPAT. Disclosures Kelly E. Pillinger, PharmD, BCIDP, Pharmacy Times (Other Financial or Material Support, Speaker)

Background OPAT service has health and economic benefits for the patient, health care facility and the general community. Management of patients receiving OPAT requires an interdisciplinary team approach and complex care coordination and has been shown to decrease adverse reaction, and rehospitalizations. Much of the work involved in caring for patients on OPAT occurs outside of a billable office visit. Describing and quantifying this workload is important to justify staffing and to advocate for change in reimbursement structure. Methods Patients enrolled in OPAT program at our clinic in 2019 were identified from the electronic medical record (EMR) and information was extracted on all EMR encounters by ID faculty and staff occurring from the start of OPAT monitoring until 14 days after OPAT ended, or until March 31, 2020 for patients still on OPAT on that date. Results During 2019, 835 unique OPAT courses were monitored for 767 patients. Activities include a sign-on process, monitoring labs, drug levels, coordinating care, weekly review by OPAT team (Medical Director or an ID attending, nurse practitioner (NP), nurse (RN) and ID pharmacist). We identified 7,640 encounters; 1,072 were office visits. Thus, 86% (N=6569) of encounters were for managing and coordinating care. The OPAT RN created 3435 of 6568 (52%) encounters, 2034 (31%) were by physicians and nurse practitioners, 500 by other clinic RNs and 599 were by administrative staff Conclusion Our results quantify the immense care for OPAT patients that is not compensated by insurance. However, this work contributes to patient safety and satisfaction. Our data does not account for time spent by the multidisciplinary team on weekly review of all active OPAT patients which lasts about 3 hours and is essential to ensuring patient safety. This data also does not quantify the contribution of the ID pharmacist who is consulted by OPAT team for multiple issues but whose recommendations are documented by the providers. The total time involved in all this work could not be determined. The quantification of the uncompensated workload of such monitoring is important as it can be justification for modernization of reimbursement for OPAT patient care, making the establishment and maintenance of such programs more financially solvent for health care organizations. Disclosures All Authors: No reported disclosures

Background Surveillance data uncovers a high proportion of multidrug-resistant Gram-negative organisms found in the outpatient setting, often in patients with recurrent urinary tract infections (UTIs), underlying urologic abnormalities, and prior treatment for UTIs. We assessed prescribing practices at urology clinics to identify potential stewardship strategies for UTI management. Methods Antibiotic prescription encounters for adult patients from nine urology clinics were obtained from July to September 2018 using the EHR. We collected encounter types (visit or nonvisit), ordering medical provider types, antibiotic classes and patient demographics. A subset of 50 randomized, unique patient telephone encounters (TEs) was reviewed for documentation of a UTI diagnosis, symptoms, urinalysis and culture results, antibiotic prescriptions and duration. Results A total of 1,704 antibiotic orders were identified for 1,210 patients (48% female, median age 69 years, IQR 20). The majority (75%) of antibiotic encounters were from nonvisits: TEs (39%), orders only (25%), refills (9%), and patient email (2%). Major prescribers were advanced practice providers (APPs, 61%) followed by attending physicians (38%). Antibiotics prescribed were fluoroquinolones (FQs, 27%), nitrofurantoin (24%), first-generation cephalosporins (16%), and trimethoprim–sulfamethoxazole (15%). From the subset of 50 TEs, APPs wrote 76% of prescriptions and 32% of all orders were FQs. Thirty-nine patients had a clinical UTI diagnosis, yet 33% (13/39) did not have documentation of at least one urinary sign or symptom. For symptomatic patients, 15% (4/26) did not have a urine culture result within one week before or after the TE date. The distribution of antibiotics prescribed was similar to overall use and the median duration was 7 days. Conclusion Urology practices care for patients with the most complicated urinary tract pathology and appropriate antibiotic use in this population is a challenge. We found that urology providers often prescribe antibiotics to elderly patients without in-person visits, documentation of symptoms or microbiologic evidence of a UTI. Stewardship efforts should involve APPs, developing diagnostic and treatment guidelines for UTIs and improving documentation for antibiotic orders. Disclosures All authors: No reported disclosures.

Background Tuberculous meningitis (TBM) is the most devastating clinical presentation of infection with Mycobacterium tuberculosis; delayed initiation of effective antituberculosis therapy is associated with poor treatment outcomes. Our objective was to determine the relationship between drug resistance and 10-year mortality among patients with TBM. Methods We conducted a retrospective cohort study of 324 patients with culture-confirmed TBM, susceptibility results reported for isoniazid and rifampin, and initiation of at least 2 antituberculosis drugs, reported to the tuberculosis registry in New York City between 1 January 1992 and 31 December 2001. Date of death was ascertained by matching the tuberculosis registry with death certificate data for 1992-2012 from the New York Office of Vital Statistics. Human immunodeficiency virus (HIV) status was ascertained by medical records review, matching with the New York City HIV Surveillance registry, and review of cause of death. Results Among 257 TBM patients without rifampin-resistant isolates, isoniazid resistance was associated with mortality after the first 60 days of treatment when controlling for age and HIV infection (adjusted hazard ratio, 1.94 [95% confidence interval, 1.08-3.94]). Death occurred before completion of antituberculosis therapy in 63 of 67 TBM patients (94%) with rifampin-resistant disease. Conclusions Among patients with culture-confirmed TBM, we observed rapid early mortality in patients with rifampin-resistant isolates, and an independent association between isoniazid-resistant isolates and death after 60 days of therapy. These findings support the continued evaluation of rapid diagnostic techniques and the empiric addition of second-line drugs for patients with clinically suspected drug-resistant TBM.

Background Our institution uses Epic as its electronic medical record (EMR), and managing the complex needs of OPAT patient’s has been challenging and also time-consuming with our EMR. It became imperative that the EMR be modified to capture all OPAT patients and manage them efficiently. We describe the development of EMR tools to facilitate OPAT management. Methods The infectious diseases (ID) physician and pharmacist identified multiple ways in which OPAT patient care could be improved by modifying the EMR. In 2016, a multidisciplinary team at URMC created software modifications in Epic to meet the needs of the OPAT program. Results A shared system list and communication tools used by ID physicians, nurses, and pharmacists were created. As soon as an inpatient is identified as an OPAT discharge, an OPAT “Plan of care” note is created by an ID fellow, note is sent to the OPAT team members (OPAT nurse, nurse practitioner, and ID pharmacist) and the patient is added to the shared list. An order set was built to facilitate accurate electronic prescribing of antimicrobials, supplies for home infusions, and pertinent laboratory tests. The order set sends an automatic message to OPAT team members, a back-up method for identifying OPAT patients. A comprehensive patient report, the “OPAT monitoring” view, was designed to facilitate patient care. The view displays OPAT relevant data from multiple sections of the patient chart onto one screen (ID notes, laboratory results, medications, appointments, free text box, etc.) without entering each patient’s chart. These EMR modifications significantly reduced the time needed for weekly case reviews and facilitates more efficient management of 90–100 patients weekly. Conclusion Modifications made to the Epic EMR at our institution have improved patient safety and efficiency of the OPAT program. Fewer patients are missed, patient monitoring is enhanced, clinician time is saved, and ordering is more accurate. Physician satisfaction was improved by creating tools that were designed with workflow efficiency in mind. These modifications were independent of and predate the recommendations made in the Epic “OPAT setup and support guide,” and provide more enhancements for efficient patient management, and could easily be made by other Epic users. Disclosures All authors: No reported disclosures.

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 ≥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.

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 assay's 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

BACKGROUND We aimed to increase human immunodeficiency virus (HIV) counseling, testing, referral (CTR), and knowledge of HIV serostatus of close contacts of tuberculosis patients and improve tuberculosis screening and treatment of HIV-infected contacts. METHODS Of close contacts to infectious tuberculosis patients reported from December 2002 to November 2003, investigators (1) offered HIV CTR, (2) identified factors associated with HIV testing, and (3) assessed study costs. RESULTS Of 614 contacts, 569 (93%) were provided HIV information and offered HIV CTR. Of the 569, 58 (10%) were previously HIV tested; 165 (29%) were newly HIV tested; and 346 (61%) were not tested. None of the 165 newly HIV tested contacts were HIV infected. Contacts more likely to be newly HIV tested (vs not tested) included those aged 18-24, Hispanic, or non-Hispanic Black. Of 24 HIV-infected contacts, 71 percent received chest-radiograph screening for tuberculosis disease; 56 percent of 18 eligible for latent-tuberculosis-infection treatment started and half completed. It cost $1 per patient to provide HIV information and $5-$8 to offer HIV CTR. CONCLUSION The project increased HIV CTR of close contacts of infectious tuberculosis patients. The important factor for success in knowing contacts' HIV serostatus was simply for TB program staff to ask about it and offer the test to those who did not know their status.

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

We studied two large Mycobacterium tuberculosis genotype clusters associated with recent outbreaks in homeless persons to determine factors associated with these tuberculosis (TB) strains. Isolates from all culture-positive TB cases diagnosed from 1 January 2001 to 31 December 2004 were genotyped. Patients whose isolates had identical restriction fragment length polymorphism patterns and spoligotypes were considered clustered. Health department records were reviewed and reinterviews attempted for clustered cases. Patients with the Cs30 and BEs75 strains were compared to other genotypically clustered cases and to each other. The two largest genotype clusters among homeless persons were the Cs30 strain ( n = 105) and the BEs75 strain ( n = 47). Fifty-one (49%) patients with the Cs30 strain and 28 (60%) with the BEs75 strain were homeless. Compared to patients with the BEs75 strain, patients with the Cs30 strain were less likely to be respiratory acid-fast bacillus smear positive (51% versus 72%). Furthermore, patients with the BEs75 strain were more likely to be HIV infected (74% versus 42%), which suggests that most patients with this strain advanced to disease after recent infection. Cases in clusters of strains that have been circulating in the community over a long time period, such as the Cs30 strain, require additional investigation to determine whether clustering is a result of recent transmission or reactivation of remote infection.

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 ≥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.

Nosocomial tuberculosis (TB) transmission has decreased dramatically in New York State since 1992; however, health care workers (HCWs) still compose3% of TB cases.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).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.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 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.

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%; ), and the association remained significant in multivariate analysis (adjusted odds ratio [OR], 5.5; P p .007 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/mm 3 . 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.

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

Objective:To determine the prevalence of and risk factors for tuberculin skin test positivity and conversion among New York City Department of Health and Mental Hygiene employees.Design:Point-prevalence survey and prospective cohort analysis. Sentinel surveillance was conducted from March 1,1994, to December 31, 2001.Participants:HCWs in high-risk and low-risk settings for occupational TB exposure.Results:Baseline tuberculin positivity was 36.2% (600 of 1,658), 15.5% (143 of 922) among HCWs born in the United States, and 48.5% (182 of 375) among HCWs not born in the United States. There were 36 tuberculin conversions during 2,754 observation-years (rate, 1.3 per 100 person-years). For HCWs born in the United States, the risk for tuberculin conversion was greater in high-risk occupational settings compared with low-risk settings (OR 5.7; CI95, 1.7–19.2;P< .01). HCWs not born in the United States and those employed at the Office of the Chief Medical Examiner (OCME) were at high risk for baseline tuberculin positivity (OR, 3.2; CI95,1.7–5.8;P< .001); OCME HCWs (OR 4.7; CI95, 2.3–9.4;P< .001), those of Asian ethnicity (OR 4.3; CI95,1.4–13.5;P< .01), and older HCWs (OR, 1.0; CI95,1.0–1.1;p< .05) were at a higher risk for conversion.Conclusions:Although the prevalence of tuberculin positivity decreased after the peak of the recent TB epidemic in New York City, the conversion rate among HCWs in high-risk occupational settings for TB exposure was still greater than that among HCWs in low-risk settings. Continued surveillance of occupational TB infection is needed, especially among high-risk HCWs.

Objectives. To assess adherence to a 1996 health policy change, which discontinued mandatory tuberculin skin testing (TST) of new entrants to NYC primary schools and continued mandatory testing of new entrants to secondary schools. Methods. The proportion tested before (1991–1995) and after (1996–1998) the change in health policy was determined. Factors associated with TST positivity and the cost of continued testing were assessed. Results. A total of 76.6% of 551 636 new entrants to primary schools were tested in 1991–1995; slightly fewer, 71.1% of 339 958, were tested in 1996- 1998. Among new entrants to secondary schools, 31.0% of 106 463 were tested in 1991–1995 and 51.4% of 53 762 were tested in 1996–1998. The proportion who were TST-positive continued to decrease after 1996 to 1.2% among primary and 9.7% among secondary schoolchildren in 1998. Older age and birth outside the United States were associated with TST positivity. The estimated minimum cost of continued testing in primary schools was $123 152 per tuberculosis case prevented. Conclusion. An approach aimed at reducing testing of children at low risk for latent tuberculosis infection did not decrease testing of younger children. More important, older children who were more likely to be born in countries of high tuberculosis incidence were not tested. Additional efforts are needed to increase awareness among medical and school personnel to decrease testing among children who do not have risk factors for latent tuberculosis infection and to increase tuberculin testing of children who are entering school for the first time at the secondary level and do have risk factors for tuberculosis infection.

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.

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 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 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 ! ). Patients infected with HIV who received 36 weeks of treatment were more likely than those who .001 received 136 weeks to have a recurrence (7.9% vs. 1.4%, ). Clinicians should be aware of the possibility P ! .001 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.

Tuberculosis among Tibetans increased in New York City between 1995 and 1999. We examined characteristics of 68 Tibetan patients compared to 702 non-Tibetan patients from Nepal, India, or China, diagnosed between January 1995 and December 1999. The number of Tibetan patients increased each year after 1995 whereas non-Tibetans remained stable during the same period. Tibetans were younger (27 vs. 44 years), more likely to be infectious (63% vs. 46%), have multidrug resistance (7% vs. 2%) and shorter time to diagnosis after arrival (9 vs. 79 months, p < 0.01). For Tibetan patients, 68% of identified contacts were evaluated. The prevalence of tuberculosis infection was 65%. In contrast, among non-Tibetan patients 88.8% of contacts were evaluated and 45.2% were infected. Outreach efforts with community leaders and educational presentations at community events have been implemented in an effort to ensure continuity of care and completion of treatment.

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.

Physicians must balance competing ethical concerns when undocumented immigrants need health care for a communicable disease. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Street outreach in two New York City communities, Harlem and the South Bronx, between May 2001 and March 2003, provided tuberculin skin test (TST) screening to illicit drug users outside the traditional health care system. Persons who used heroin, cocaine, and/or crack were offered a TST, incentives to return for TST reading, and further evaluation if TST was positive. Of 809 participants, 530 (66%) accepted a TST and 81% (429/530) returned for TST reading. Of 429 participants, 40 (9%) were TST positive. Participants found TST positive did not differ from those found TST negative in previous drug user treatment or drug use practices including snorting heroin, sniffing cocaine, smoking crack, and injecting drugs of any kind. Of the 40 participants found TST positive, the 21 who tested TST positive for the first time were more likely to be male (p = .03) and noninjectors (p = .02), than the 19 who had tested TST positive in the past. Only two newly identified persons pursued follow-up care. Street recruitment expanded testing. Better follow-up strategies are needed. The study's limitations are noted.

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 susceptibilty 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.

BACKGROUND Although highly active antiretroviral therapy (HAART) has decreased human immunodeficiency virus (HIV)-related morbidity, tuberculosis remains an important disease among HIV-infected individuals. METHODS By use of surveillance data, sociodemographic and clinical changes among HIV-infected and HIV-uninfected tuberculosis patients in New York City were evaluated using the Cochran-Armitage trend test and multivariate logistic regression across 3 periods: 1992-1995 (pre-HAART), 1996-2000 (early HAART), and 2001-2005 (late HAART). RESULTS Among tuberculosis patients with known HIV status, 4345 (60%) of 7224 were HIV-infected in pre-HAART, 1943 (33%) of 5933 in early HAART, and 851 (22%) of 3815 in late HAART (P < .001 for trend). During the study period, the age of HIV-infected tuberculosis patients increased, and greater proportions were female, non-Hispanic black, Asian, and foreign born; the proportion that was non-Hispanic white decreased. The proportion that was culture-negative for Mycobacterium tuberculosis increased (from 7% pre-HAART to 21% late HAART; P < .001 for trend; early HAART vs pre-HAART adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.38-2.04), and the proportion with extrapulmonary disease also increased (from 32% to 46%; P < .001 for trend). The proportion with multidrug-resistant tuberculosis decreased (from 16% to 4%; P < .001 for trend), especially from pre-HAART to early HAART (aOR, 0.31; 95% CI, 0.25-0.40). The proportion who died before tuberculosis treatment decreased (from 12% to 7%), and the proportion who died during tuberculosis treatment also decreased (from 29% to 11%) (both, P < .001 for trend). Over time, HIV-infected tuberculosis patients had AIDS longer before the diagnosis of tuberculosis (P < .001 for trend). Similar trends for culture, site of disease, and drug resistance were seen for HIV-uninfected tuberculosis patients. CONCLUSIONS The sociodemographic and clinical characteristics changed substantially among HIV-infected tuberculosis patients in New York City. Awareness of these changes may speed diagnosis of tuberculosis. Future studies should evaluate HAART's effect on tuberculosis presentation among HIV-infected patients.

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.

Spoligotype analysis identified false-positive isolates ofMycobacterium tuberculosiscaused by laboratory cross-contamination. Spoligotyping is faster, is less expensive than DNA fingerprinting, and can be used with a variety of media. Patients were reevaluated and had medications discontinued as a result of this investigation. Months of unnecessary patient follow-up and treatment were avoided.

The prevalence of latent tuberculosis infection (LTBI) in the various populations of New York City (NYC), a city with a high density of non-US-born persons, is unknown. We examined the prevalence of TST positivity in patients who received a tuberculin skin test (TST) between 1/2002 and 8/2004 at any of 10 NYC health department chest centers. A positive TST was defined as an induration reaction to tuberculin of ≥10 mm. In the study population of 41,022 individuals, prevalence of TST positivity was 24.4% (95%CI = 24.0, 24.8); four times higher among non-US-born persons than US-born (39.5% vs. 8.8%, Prevalence ratio (PR) = 4.5; 95%CI = 4.4, 4.6). Prevalence of TST positivity increased with age in both US and non-US-born persons. Persons from countries with a TB case rate >100/100,000 population had higher prevalence of TST positivity (47% vs. ≤39%), even after controlling for BCG (PR = 1.3, 95%CI = 1.2, 1.4). These findings provide insight into current prevalence of TST positivity in many immigrant populations and will help both clinicians and health departments to target patients for LTBI treatment.

SUMMARYTuberculosis incidence in New York City (NYC) declined between 1992 and 2000 from 51·1 to 16·6 cases per 100 000 population. In January 2001, universal real-time genotyping of TB cases was implemented in NYC. Isolates from culture-confirmed tuberculosis cases from 2001 to 2003 were genotyped using IS6110and spoligotype to describe the extent and factors associated with genotype clustering after declining TB incidence. Of 2408 (91·8%) genotyped case isolates, 873 (36·2%) had a pattern indistinguishable from that of another study period case, forming 212 clusters; 248 (28·4%) of the clustered cases had strains believed to have been widely transmitted during the epidemic years in the early 1990s in NYC. An estimated 27·4% (873 minus 212) of the 2408 cases were due to recent infection that progressed to active disease during the study period. Younger age, birth in the United States, homelessness, substance abuse and presence of TB symptoms were independently associated with greater odds of clustering.

Real-time universal genotyping decreased unnecessary treatment., In 2001, New York City implemented genotyping to its tuberculosis (TB) control activities by using IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping to type isolates from culture-positive TB patients. Results are used to identify previously unknown links among genotypically clustered patients, unidentified sites of transmission, and potential false-positive cultures. From 2001 to 2003, spoligotype and IS6110-based RFLP results were obtained for 90.7% of eligible and 93.7% of submitted isolates. Fifty-nine (2.4%) of 2,437 patient isolates had false-positive culture results, and 205 genotype clusters were identified, with 2–81 cases per cluster. Cluster investigations yielded 57 additional links and 17 additional sites of transmission. Four additional TB cases were identified as a result of case finding initiated through cluster investigations. Length of unnecessary treatment decreased among patients with false-positive cultures.

Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans.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.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.The primary endpoint was sputum culture status at 2 mo of treatment.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.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.

Factors influencing tuberculosis cluster growth are poorly understood. The authors examined clusters of two or more culture-confirmed Mycobacterium tuberculosis cases between January 1, 2001, and December 31, 2003, that had insertion sequence 6110 (IS6110) restriction fragment length polymorphism and spoligotype patterns identical to those of another study case. Genotypes first seen in New York, New York, before or during 1993 were considered historical; recent strains were those first seen after 1993. The authors examined the effect of the combined characteristics of infectiousness of the first two cases in a cluster on the rate of cluster growth. Genotyping was performed for 2,408 (91.8%) of the 2,623 tuberculosis cases diagnosed; 873 cases were in 212 clusters. Thirty-one clusters had historical strains, 153 were recent, and 28 were of unknown period. Patients' infectiousness was not associated with the rate of cluster growth among historical strain clusters. Among recent strain clusters, infectiousness of both of the initial cases was associated with a higher rate of cluster growth compared with clusters in which neither initial case was infectious, upon adjustment for male sex (rate ratio = 2.62, 95% confidence interval: 1.19, 5.78). The rate of genotype cluster growth should be monitored regardless of how long the strain has been present in the community. However, infectiousness in the first two cases may be useful to prioritize genotype cluster investigations.

This article reviews the principles, scientific basis, and experience with implementation of the directly observed treatment strategy, short course (DOTS) for tuberculosis. The relevance of DOTS in the context of multidrug-resistant tuberculosis and the HIV epidemic also is discussed.

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.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.A municipal TB control program.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.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 (p0.05) 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.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.

Among communicable diseases, tuberculosis is the second leading cause of death worldwide, killing nearly 2 million people each year. Most cases are in less-developed countries; over the past decade, tuberculosis incidence has increased in Africa, mainly as a result of the burden of HIV infection, and in the former Soviet Union, owing to socioeconomic change and decline of the health-care system. Definitive diagnosis of tuberculosis remains based on culture for Mycobacterium tuberculosis, but rapid diagnosis of infectious tuberculosis by simple sputum smear for acid-fast bacilli remains an important tool, and more rapid molecular techniques hold promise. Treatment with several drugs for 6 months or more can cure more than 95% of patients; direct observation of treatment, a component of the recommended five-element DOTS strategy, is judged to be the standard of care by most authorities, but currently only a third of cases worldwide are treated under this approach. Systematic monitoring of case detection and treatment outcomes is essential to effective service delivery. The proportion of patients diagnosed and treated effectively has increased greatly over the past decade but is still far short of global targets. Efforts to develop more effective tuberculosis vaccines are under way, but even if one is identified, more effective treatment systems are likely to be required for decades. Other modes of tuberculosis control, such as treatment of latent infection, have a potentially important role in some contexts. Until tuberculosis is controlled worldwide, it will continue to be a major killer in less-developed countries and a constant threat in most of the more-developed countries.

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.

OBJECTIVE To determine whether active tuberculosis alters the rate of progression of HIV infection in dually infected patients. METHODS HIV-seropositive patients at two Bronx, New York hospitals with tuberculosis confirmed by culture from July 1992 to February 1995, who survived the initial hospitalization for tuberculosis, were matched on gender, age, CD4+ percentage, and calendar time with HIV-seropositive patients without tuberculosis participating in a study of the natural history of HIV infection. Patients received follow-up observation prospectively until May 23, 1995 to determine survival rates and development of AIDS-defining opportunistic infections (OIs). RESULTS 70 patients had tuberculosis; 120 did not. Mean CD4+ percentages were 12.4% and 12.5%, respectively. At study entry, 27% of those with tuberculosis had prior AIDS-defining OIs other than tuberculosis, compared with 10% of those without tuberculosis (p = .004). In multivariate survival analysis, controlling for CD4+ level, tuberculosis was not an independent predictor of increased other causes of AIDS-related mortality. However, in a logistic regression model, independent predictors of subsequent OIs included tuberculosis (hazard ratio, 4.1; 95% confidence intervals [CI], 1.9, 8.7), CD4+ count

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.

We prospectively studied the effect of human immunodeficiency virus (HIV) infection on the presentation and outcome of tuberculosis. A total of 216 patients with tuberculosis were identified; 162 (75%) of these patients were tested for antibodies to HIV; 92 (57%) were seropositive. The patients who were seropositive for HIV were more likely to be male and Hispanic and to have been homeless or incarcerated. Eighty-one percent of these patients had CD4 lymphocyte counts of < or =200/mm3. The seropositive patients had extrapulmonary tuberculosis more often than did the seronegative patients (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.8). Smears for acid-fast bacilli were positive more often for non-HIV-infected patients with pulmonary tuberculosis (74.5%) than for HIV-infected patients (54.3%) [OR, 2.46; 95% CI, 1.01-6.02]-even those with focal or cavitary disease. A delay in initiating therapy was associated with in-hospital mortality: the median time from admission to the start of treatment was 4 days for patients who survived and 15 days for those who died (P = .02). The median survival was 22.7 months for HIV-infected patients who did not die during the initial hospitalization. Factors independently associated with reduced rates of survival included the severity of immunodeficiency, nonuse of directly observed therapy, infection due to drug-resistant Mycobacterium tuberculosis, and a history of injection drug use.