Samuel W. Dooley

The Emergence of Drug-Resistant Tuberculosis in New York City

BACKGROUND In the past decade the incidence of tuberculosis has increased nationwide and more than doubled in New York City, where there have been recent nosocomial outbreaks of multidrug-resistant tuberculosis. METHODS We collected information on every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1991. Drug-susceptibility testing was performed at the Centers for Disease Control and Prevention. RESULTS Of the 518 patients with positive cultures, 466 (90 percent) had isolates available for testing. Overall, 33 percent of these patients had isolates resistant to one or more antituberculosis drugs, 26 percent had isolates resistant to at least isoniazid, and 19 percent had isolates resistant to both isoniazid and rifampin. Of the 239 patients who had received antituberculosis therapy, 44 percent had isolates resistant to one or more drugs and 30 percent had isolates resistant to both isoniazid and rifampin. Among the patients who had never been treated, the proportion with resistance to one or more drugs increased from 10 percent in 1982 through 1984 to 23 percent in 1991 (P = 0.003). Patients who had never been treated and who were infected with the human immunodeficiency virus (HIV) or reported injection-drug use were more likely to have resistant isolates. Among patients with the acquired immunodeficiency syndrome, those with resistant isolates were more likely to die during follow-up through January 1992 (80 percent vs. 47 percent, P = 0.02). A history of antituberculosis therapy was the strongest predictor of the presence of resistant organisms (odds ratio, 2.7; P < 0.001). CONCLUSIONS There has been a marked increase in drug-resistant tuberculosis in New York City. Previously treated patients, those infected with HIV, and injection-drug users are at increased risk for drug resistance. Measures to control and prevent drug-resistant tuberculosis are urgently needed.

Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis : a risk to patients and health care workers

OBJECTIVE To determine the factors associated with the development of multidrug-resistant tuberculosis among patients at a New York City Hospital and to investigate possible nosocomial transmission. DESIGN A retrospective case-control study and tuberculin skin test survey. PATIENTS Twenty-three patients with tuberculosis whose isolates were resistant to at least isoniazid and rifampin (case patients) were compared with patients with tuberculosis whose isolates were susceptible to all agents tested (controls). Tuberculin skin test conversion rates were compared among health care workers assigned to wards where patients with tuberculosis were frequently or rarely admitted. SETTING A large, teaching hospital in New York City. MEASUREMENTS Mycobacterium tuberculosis isolates from case patients and controls were typed by restriction fragment length polymorphism analysis. RESULTS Case patients were younger (median age, 34 compared with 42 years; P = 0.006), more likely to be seropositive for HIV (21 of 23 compared with 11 of 23 patients; odds ratio, 11.5; 95% CI, 1.9 to 117), and more likely to have had a previous hospital admission within 7 months before the onset of tuberculosis (19 of 23 compared with 5 of 23 patients; odds ratio, 17.1; CI, 3.3 to 97), particularly on one ward (12 of 23 compared with 0 of 23 patients; odds ratio, undefined; P = 0.002). Health care workers assigned to wards housing case patients were more likely to have tuberculin skin test conversions than were health care workers assigned to other wards (11 of 32 compared with 1 of 47 health care workers; P less than 0.001). Few (6 of 23) case patients were placed in acid-fast bacilli isolation, and no rooms tested had negative pressure. Of 16 available multidrug-resistant isolates obtained from case patients, 14 had identical banding patterns by restriction fragment length polymorphism analysis. In contrast, M. tuberculosis isolates from controls with drug-susceptible tuberculosis had patterns distinct from each other and from those of case patients. CONCLUSIONS These data suggest nosocomial transmission of multidrug-resistant tuberculosis occurred from patient to patient and from patient to health care worker and underscore the need for effective acid-fast bacilli isolation facilities and adherence to published infection control guidelines in health care institutions.

Multidrug-resistant Tuberculosis

Excerpt As recently as 10 years ago, tuberculosis was rapidly disappearing from the United States. Reported cases of tuberculosis were decreasing an average of almost 6% each year, from over 84 000...

Nosocomial tuberculosis: an outbreak of a strain resistant to seven drugs.

OBJECTIVE To evaluate nosocomial transmission of multidrug-resistant (MDR) tuberculosis (TB). DESIGN Outbreak investigation: review of infection control practices and skin test results of healthcare workers (HCWs); medical records of hospitalized TB patients and mycobacteriology reports; submission of specimens for restriction fragment length polymorphism (RFLP) typing; and an assessment of the air-handling system. SETTING A teaching hospital in upstate New York. RESULTS Skin-test conversions occurred among 46 (6.6%) of 696 HCWs tested from August through October 1991. Rates were highest on two units (29% and 20%); HCWs primarily assigned to these units had a higher risk for conversion compared with HCWs tested following previous incidents of exposure to TB (relative risk [RR] = 53.4, 95% confidence interval [CI95] = 6.9 to 411.1; and RR = 37.4, CI95 = 5.0 to 277.3, respectively). The likely source patient was the only TB patient hospitalized on both units during the probable exposure period. This patient appeared clinically infectious, was associated with a higher risk of conversion among HCWs providing direct care (RR = 2.37; CI95 = 1.05 to 5.34), and was a prison inmate with TB resistant to seven antituberculosis agents. The MDR-TB strain isolated from this patient also was isolated from other inmate and noninmate patients, and a prison correctional officer exposed in the hospital. Mycobacterium tuberculosis isolates from all of these patients had matching RFLP patterns. Infection control practices closely followed established guidelines; however, several rooms housing TB patients had marginal negative pressure with variable numbers of air changes per hour, and directional airflow was disrupted easily. CONCLUSIONS These data strongly suggest nosocomial transmission of MDR-TB to HCWs, patients, and a prison correctional officer working in the hospital. Factors contributing to transmission apparently included prolonged infectiousness of the likely source patient and inadequate environmental controls. Continued urgent attention to TB infection control is needed.

Respirators, Recommendations, and Regulations: The Controversy Surrounding Protection of Health Care Workers from Tuberculosis

During the past 5 years, tuberculosis has reemerged as a major public health problem [1, 2]. Numerous nosocomial outbreaks of tuberculosis have been reported and have often involved multidrug-resistant strains of Mycobacterium tuberculosis [3-8]. In outbreaks of multidrug-resistant tuberculosis investigated by the Centers for Disease Control and Prevention (CDC), more than 100 health care workers have had tuberculin skin-test conversions, at least 17 have developed active multidrug-resistant tuberculosis, and at least 6 have died [8]. Because of concern about the risk for occupational acquisition of tuberculosis by workers in health care facilities, the various federal agencies responsible for the protection of these workers have issued recommendations, guidelines, and compliance memoranda outlining various protective measures. Each of these agencies has recommended some type of respiratory protective device to be worn by health care workers (Tables 1 and 2); at times these recommendations have appeared contradictory and have led to confusion. Our purpose is to describe both the evolution of these recommendations and the role of each federal agency in respiratory protection for health care workers. Table 1. Summary Comparison of Four Respirator Types Evaluated for Protection of Health Care Workers Potentially Exposed to Tuberculosis* Table 2. Summary Comparison of Three Types of Negative-Pressure Respirators The CDC Tuberculosis Guidelines The CDC is a nonregulatory federal agency responsible for developing practical guidelines for the prevention of disease transmission. In 1982, it published Guidelines for Prevention of TB Transmission in Hospitals, in which it recommended surgical masks for the protection of health care workers [9]. Because nosocomial transmission of tuberculosis was reported infrequently and surgical masks were used to protect patients from health care workers, to protect health care workers from patients, and as source control to contain droplet nuclei in patients with tuberculosis, there was little evaluation of the type of respiratory protection recommended to protect health care workers from tuberculosis. However, as the 1982 Guidelines for Prevention of TB Transmission in Hospitals was being revised in 1989 by representatives of the National Center for Infectious Diseases (NCID), the National Center for Prevention Services (NCPS), and the National Institute for Occupational Safety and Health (NIOSH)all of which are part of the CDCnosocomial outbreaks of drug-susceptible and multidrug-resistant tuberculosis began to be reported [3-8, 10]. In 1990, the CDC published Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Settings, with Special Focus on HIV-related Issues [11]. The 1990 Guidelines stated that standard surgical masks may not be effective in preventing inhalation of droplet nuclei and recommended the use of disposable particulate respirators while acknowledging that the efficacy of particulate respirators in protecting susceptible persons from inhalation of tuberculosis has not been demonstrated. The term particulate respirator was defined as a disposable respiratory protective device designed to filter out particles 1 to 5min diameter; no specific reference was made to the three classes of filtersdust-mist, dust-fume-mist, and high-efficiency particulate aircertified under federal regulations (31 CFR Part 11) published in 1972. Use of the generic term particulate respirator implied that the use of any of these three filters would satisfy the 1990 guidelines. Dust-Mist and Dust-Fume-Mist Filters: 1992 NIOSH Draft Report In a 1992 draft report, NIOSH presented peer-reviewed data showing that the filters of certain dust-mist and dust-fume-mist respirators allowed significant leakage of small particles ( 2 microns). Public health concern about the data arose because these small particles are also likely to reach the lungs of workers. Occupational Safety and Health Administration Requests NIOSH Respirator Recommendation As more outbreaks of multidrug-resistant tuberculosis were reported, concern about occupational acquisition of tuberculosis increased. The Occupational Safety and Health Administration (OSHA), the federal agency with legislatively established regulatory responsibility for workplace safety and health, responded to complaints (mainly from workers in New York State) and did inspections relevant to occupational exposure to tuberculosis. In May 1992, OSHA Region II issued enforcement guidelines for such occupational exposure, in which it specified the minimal recommended level of respiratory protection to be that provided by dust-fume-mist respirators. In August 1992, OSHA formally requested NIOSH to state which respirators health care workers should be required to wear to prevent occupational acquisition of tuberculosis (OSHA requires use of NIOSH-certified respirators). A nonregulatory federal agency responsible for research and training in occupational safety and health, NIOSH also has a statutory responsibility to provide a scientific basis for criteria it recommends to OSHA, criteria that OSHA uses to develop workplace standards. In addition, NIOSH has regulatory responsibility for respirator certification. Response of NIOSH to OSHA Request In August 1992, NIOSH issued Recommended Guidelines for Personal Protection of Workers in Health Care Facilities Potentially Exposed to Tuberculosis [12]. Believing that it was legally mandated that recommendations should eliminate all risk for infection without considering cost or practicality, NIOSH recommended the use of NIOSH-certified, powered, half-mask respirators equipped with high-efficiency particulate air filters in areas where patients known or suspected to have tuberculosis were receiving care. In the most hazardous locations and during the most hazardous procedures (such as bronchoscopy and sputum induction), NIOSH recommended the use of NIOSH-certified, positive-pressure, air-line, half-mask respirators. It also recommended that all respirators be used in conjunction with an effective respiratory protection program [12-15]. These recommendations were made because many important factors, including the size of the infectious droplet nuclei, the concentration of bacteria released by infectious patients, the permissible (maximum) exposure limit, and the threshold (minimum) limit were unknown; the likelihood of faceseal leakage of nonpowered respirators was thought to be substantial; and the NIOSH respirator decision logic excluded the use of less effective respirators. The CDC Examines the Need for Revision of Its 1990 Tuberculosis Guidelines Transmission of tuberculosis from patient to patient and from patient to health care worker raised concerns about the adequacy of the CDCs 1990 guidelines. Thus, in October 1992, the CDC held a meeting to discuss whether the 1990 guidelines should be revised. The initial outbreaks of multidrug-resistant tuberculosis were discussed and follow-up data from one hospital were presented; these data showed that if the 1990 guidelines were fully implemented (including those requiring the use of source and engineering controls and molded surgical or high-efficiency laser surgical masks or dust-mist respirators), nosocomial transmission of multidrug-resistant tuberculosis from patient to patient or from patient to health care worker would cease [16]. Additionally, NIOSH presented their respirator recommendations and the rationale behind them. At the conclusion of the meeting, the Director of the CDC stated that although they need some revision, the basic thrust of the CDC 1990 Guidelines is about right. It has also been made clear that the 1990 Guidelines have not yet been widely put in place. He recommended wider implementation of the 1990 CDC tuberculosis guidelines and a reinforcement in the revised guidelines of the hierarchy of controls, health care worker education, and the role of source and engineering controls. A CDC Tuberculosis Guideline Working Group that included representatives from NCID, NCPS, and NIOSH was charged with revising the 1990 CDC tuberculosis guidelines. The CDC Publishes 1993 Draft Guidelines On 12 October 1993, the CDC published Draft Guidelines for Preventing Transmission of Tuberculosis in Health-Care Facilities, second edition, in the Federal Register for public comment [17]. The Draft Guidelines emphasized the hierarchy of controls needed to prevent transmission of tuberculosis. Performance criteria were outlined for personal respiratory protection in situations where administrative and engineering controls may not provide sufficient protection. Performance criteria for respirators were as follows: 1) the ability to filter particles 1min size with an efficiency of at least 95%; 2) the ability to be qualitatively or quantitatively tested for fit in a reliable way; 3) the ability to fit test health care workers with different facial sizes and characteristics; and 4) to ensure proper protection, the ability to have facepiece fit checked by the wearer each time the respirator is worn. These criteria were based on the characteristics of respirators that were used in conjunction with source and engineering controls in outbreak settings where the transmission of tuberculosis to health care workers had been reduced or terminated. The 1993 Draft Guidelines stated that some dust-mist or dust-fume-mist respirators might meet the performance criteria. In addition, evidence was obtained from two hospitals that had had outbreaks of multidrug-resistant tuberculosis; this evidence showed that implementation of a program satisfying CDC recommendations for source and engineering controls and including the use of dust-mist respirators that met the 1993 Draft Guidelines criteria terminated transmission of tuberculosis to health care workers. However, only high-efficiency particulate air filter respirators are certified by NIOSH (as required by OSHA) and

Effect of HIV Infection and Tuberculosis on Hospitalizations and Cost of Care for Young Adults in the United States, 1985 to 1990

An estimated 1 million persons in the United States are infected with human immunodeficiency virus (HIV) [1], and 10 million are infected with Mycobacterium tuberculosis (CDC. Unpublished data). From 1985 to 1993, the number of reported cases of tuberculosis increased by more than 14%, reversing a 30-year period of steady decline [2, 3]. The resurgence of tuberculosis in the United States can be attributed in part to the HIV epidemic, which has fueled increases in tuberculosis morbidity in certain racial and ethnic, age, and geographic populations [4-7]. Infection with HIV dramatically increases the risk that latent tuberculosis infection, either new or preexisting, will progress to tuberculosis disease [6, 7]. In addition, progression of disease from tuberculosis infection is facilitated by factors associated with the HIV epidemic, such as injecting drug use, which has been reported in 26% of the young adults diagnosed with the acquired immunodeficiency syndrome (AIDS) since 1990 [8]. Tuberculosis has become a common opportunistic disease among persons with HIV infection, especially in developing countries [9]; in the United States, 5% of persons reported as having AIDS between 1978 and 1990 were also reported as having tuberculosis [10]. Since 1990, several outbreaks of multidrug-resistant tuberculosis among hospitalized persons with HIV infection have resulted in substantial morbidity and mortality [2, 11-16]. The co-epidemics of HIV infection and tuberculosis have had an increasing effect on morbidity among young adults. From 1985 to 1990, 80% of persons diagnosed with AIDS were 15 to 44 years of age [8]; similarly, from 1985 to 1992, the largest increase in cases of tuberculosis (54%) was seen in persons 25 to 44 years old [4]. In our study, we evaluated the effect of HIV infection and tuberculosis on hospitalizations and cost of care. Because these epidemics converge in young adults, we focused on persons 15 to 44 years of age. In previous studies, the rate of HIV hospitalization was estimated from a nationally representative sample of hospitals [17]; however, estimates of the cost of HIV inpatient care and national projections of the cost of inpatient care for persons with AIDS have been based on information from selected hospitals [18-21]. In addition, no national estimates of the cost of tuberculosis inpatient care exist. In our study, we used both cost data and a nationally representative survey of hospitals to estimate hospitalizations and the cost of HIV infection and tuberculosis care. Methods Data were obtained from the National Hospital Discharge Survey (NHDS), a nationally representative probability survey of discharges from nonfederal short-stay general and specialty hospitals in 50 states and the District of Columbia. From a total of approximately 6000 U.S. short-stay hospitals, a sample of about 500 hospitals was obtained for each year of the analysis [22]. The NHDS survey design has previously been described in detail [22]. Before 1988, a two-stage survey was used to select hospitals and sample discharges within hospitals. In 1988, the design was changed to a three-stage sample to select geographic locations within regions, hospitals, and discharges within hospitals [22]. Modification of the survey design in 1988 may affect the evaluation of trends [22]. Each hospital discharge record lists from 1 to 7 diagnoses, coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) [23]. Tuberculosis hospitalizations were defined as those for which discharge records listed a diagnosis of tuberculosis (ICD-9-CM codes 010-018). Records listing primary tuberculosis complex (code 010.0), primary tuberculosis infection (010.9), or tuberculosis of the skin (017.0), which account for approximately 11% of records listing tuberculosis, were excluded because they could have represented tuberculosis infection without disease. Hospitalizations for pulmonary tuberculosis were those for which discharge records listed a diagnosis of pulmonary tuberculosis without extrapulmonary tuberculosis. Extrapulmonary tuberculosis hospitalizations were those for which discharge records listed a diagnosis of extrapulmonary tuberculosis with or without pulmonary tuberculosis. Human immunodeficiency virus hospitalizations were defined as those for which records listed HIV infection (ICD-9-CM codes 042-044, 279.19 or 795.8) [24]. The number of AIDS-related hospitalizations was estimated from the number of records listing ICD-9-CM codes designated for AIDS (042 or 279.19) and the number listing an HIV infection code concurrently with an illness that was a part of the 1987 CDC AIDS surveillance definition [25]. Hospitalizations related to drug abuse or drug dependence were defined as those for which records listed a diagnosis of drug dependence (ICD-9-CM code 304) or nondependent drug abuse (305.2-305.9) and did not include those in which records listed alcohol abuse or dependence. Analyses included hospitalizations for which records listed HIV infection or active tuberculosis among adults 15 to 44 years of age (young adults) during 1985-1990, and were based on 3990 sampled records, corresponding to a weighted national estimate of 479 700 hospitalizations or patients. The unit of analysis was the hospitalization or the patient, not the person, because persons could have more than one hospitalization. Hospitalization rates were estimated by using the number of NHDS hospitalizations and U.S. census population data [26]. Geographic regions were those defined by the U.S. Census Bureau. To estimate the direct costs of inpatient care, data on hospital daily charges (which included facility fees) were obtained from 1990 statewide hospital billing information for HIV infection and tuberculosis from 18 states: Arizona, California, Colorado, Florida, Illinois, Maine, Maryland, Massachusetts, Nevada, New Hampshire, New Jersey, New York, Oregon, Pennsylvania, South Carolina, Vermont, Washington, and Wisconsin (Personal communication, 2 October, 1992. Spitzer M, Codman Research Inc.). Inpatient HIV care costs were estimated by aggregating regional estimates. Regional rather than statewide estimates were derived because of the observed variation in cost by region and because estimates of the number of NHDS hospitalization days were available for regions, not states. We calculated the HIV care cost for each region by multiplying its number of NHDS HIV hospitalization days by its estimated daily cost of HIV care. This regional daily cost of HIV care was estimated from the statewide billing database by determining an average of the state-specific daily HIV care costs weighted by the number of HIV hospitalization days in the state. Because the daily cost of HIV inpatient care was similar for persons with and without AIDS, these groups were analyzed in aggregate. The same procedure was used for estimating tuberculosis inpatient care costs. Although cost data were available for only 18 states, these states accounted for 71% of AIDS cases and 72% of tuberculosis cases among adults 15 to 44 years of age within the jurisdiction of NHDS during 1985-1990 [8, 27]. However, because cost data were not available for all states, we did a sensitivity analysis to assess the effect of geographic variations in costs on our national cost estimate. Two methods were used to estimate inpatient care costs for the 6-year period 1985-1990. In method I, the 1990 hospital costs were applied to all years of data. Regional weighted average 1990 daily costs for HIV infection and tuberculosis were, respectively,

An Outbreak of Multidrug-Resistant Tuberculosis among Hospitalized Patients with the Acquired Immunodeficiency Syndrome

820 and

Hospital Outbreak of Multidrug-Resistant Mycobacterium tuberculosis Infections: Factors in Transmission to Staff and HIV-Infected Patients

740 in the North,

Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Settings, with Special Focus on HIV-Related Issues

1460 and

Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients.

1190 in the Midwest,