Efficacy of Control Measures in Preventing Nosocomial Transmission of Multidrug-Resistant Tuberculosis to Patients and Health Care Workers

Nosocomial transmission of Mycobacterium tuberculosis, particularly transmission of multidrug-resistant strains, to patients and health care workers is a major public health problem [1-12]. From 1990 through 1992, the Centers for Disease Control and Prevention (CDC) investigated eight outbreaks of multidrug-resistant tuberculosis in U.S. hospitals (1-6; CDC, unpublished data). More than 300 patients with multidrug-resistant tuberculosis were identified during these investigations; most (87%) were infected with human immunodeficiency virus (HIV). Their clinical course was characterized by rapid progression from infection to active tuberculosis and their mortality rate was high [9]. Additionally, more than 100 health care workers at hospitals where outbreaks of multidrug-resistant tuberculosis had occurred had conversion of their tuberculin skin tests, suggesting recently acquired M. tuberculosis infection. At least 17 of these newly infected health care workers developed active multidrug-resistant M. tuberculosis, and at least 7 of them died with multidrug-resistant tuberculosis [10]. Because of the explosive and fatal nature of these recent nosocomial outbreaks of multidrug-resistant tuberculosis, questions have been raised about the most effective interventions and control measures necessary to prevent institutional transmission of tuberculosis [13-15]. We evaluated the efficacy of control measures for decreasing the transmission of these multidrug-resistant M. tuberculosis strains in one of the hospitals that had had an outbreak. Methods In May 1991, we investigated an outbreak of multidrug-resistant tuberculosis at Cabrini Medical Center, a teaching hospital in New York City. In that investigation, epidemiologic and laboratory data showed the occurrence of nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers [5]. Risk factors for acquisition of multidrug-resistant tuberculosis by patients included age, HIV seropositivity, and hospital admission to Cabrini Medical Center within 7 months before onset of multidrug-resistant tuberculosis. Additionally, health care workers assigned to the medical or HIV wards (primary wards housing patients with tuberculosis) were identified as being at increased risk for tuberculin skin test conversion. Conditions facilitating tuberculosis transmission included delayed identification, isolation, or treatment of patients with infectious tuberculosis; lapses in tuberculosis isolation practices; and inadequate isolation facilities for patients with tuberculosis. In response to the outbreak, control measures similar to those recommended in the CDC's 1990 tuberculosis guidelines were instituted to prevent further nosocomial transmission of tuberculosis [16]. Control Measures Numerous measures were introduced to decrease transmission of multidrug-resistant tuberculosis, including source controls, environmental controls, and respiratory protection for health care workers (Table 1). Source control measures included improved isolation precautions and expanded treatment regimens for patients with suspected or confirmed tuberculosis and included routine use of acid-fast bacilli smears to determine length of isolation and to establish treatment efficacy. To expedite the identification of patients with infectious tuberculosis and the determination of the antimicrobial susceptibility of M. tuberculosis isolates, laboratory procedures were also modified. Thus, personnel and workday hours devoted to processing of mycobacterial isolates were expanded; a hospital-wide computerized database of patients with tuberculosis was developed; a gene probe was introduced; and the reporting of acid-fast bacilli smear results to requesting physicians was standardized. Table 1. Infection Control Measures* Environmental modifications included installing exhaust fans in isolation rooms to increase the number of acid-fast bacilli isolation rooms with negative pressure and included using portable Aeroguard (HR Incorporated, Bellevue, Washington) chambers to do cough-inducing procedures, such as sputum induction or aerosolized pentamidine administration. Finally, to further decrease the risk for occupational acquisition of tuberculosis, the respiratory protection worn by health care workers was changed from nonmolded to molded surgical masks (3M 1800+ Aseptex, 3M Incorporated, St. Paul, Minnesota). To assess compliance with these control measures, we examined the hospital's isolation facilities, reviewed patient charts for documentation of initiation and discontinuation of acid-fast bacilli isolation precautions, interviewed infection control and laboratory personnel, observed isolation practices on hospital wards containing patients with tuberculosis, and evaluated the ventilation system in acid-fast bacilli isolation rooms by testing air-flow direction using smoke tubes. Epidemiologic Studies A case-patient was defined as any Cabrini Medical Center patient whose M. tuberculosis isolate was resistant to at least isoniazid and rifampin and as any patient whose clinical course was consistent with active tuberculosis during the study period (1 January 1990 to 11 August 1992). Case-patients and all other patients with tuberculosis were identified by reviewing Cabrini Medical Center laboratory and infection control records during the study period. Medical records of all potential case-patients were reviewed to verify a clinical course consistent with tuberculosis. To determine whether a decrease had occurred in the incidence of multidrug-resistant tuberculosis after the institution of control measures, we compared the proportion of patients with tuberculosis who had multidrug-resistant strains before (preintervention period) and after (intervention period) the implementation of control measures. The preintervention period (January 1990 to June 1991) was defined as the time from the onset of the outbreak until the formal institution of recommended control measures; the intervention period (July 1991 to 11 August 1992) was defined as the time during and after the institution of recommended control measures until our follow-up study. Patient-to-Patient Transmission To investigate possible patient-to-patient transmission of multidrug-resistant tuberculosis, we evaluated case-patient medical records to determine if case-patients had been hospitalized at Cabrini Medical Center within 7 months before onset of tuberculosis. For those case-patients who had been previously hospitalized, we determined whether they had been hospitalized on the same ward at the same time or whether they had a documented nosocomial exposure to another patient with culture-confirmed multidrug-resistant tuberculosis during a previous hospitalization. Data collected included age, sex, race, HIV serologic status, previous opportunistic infections, dates and results of acid-fast bacilli smears and mycobacterial cultures, M. tuberculosis antimicrobial susceptibilities, dates of admission and discharge, hospital room assignments, dates of isolation for tuberculosis, nursing documentation of proper application of isolation precautions, antituberculous medications prescribed, clinical course, and outcome. Patient-to-Health Care Worker Transmission To evaluate whether the risk for transmission of multidrug-resistant tuberculosis from patients to health care workers had been reduced, we compared conversion rates of tuberculin skin tests in health care workers during the preintervention and intervention periods. During both periods, the tuberculin skin testing program at Cabrini Medical Center required annual testing of all hospital employees and additional testing of health care workers after a known tuberculosis exposure. A tuberculin skin test conversion was defined as induration of 10 mm or more to purified protein derivative in a Cabrini Medical Center employee with a documented tuberculin skin test result that was negative within the previous 24 months. Employees without negative skin test results at baseline were excluded from our analyses. Conversion rates were compared by period, by job category (frequent direct patient contact compared with infrequent or no direct patient contact), and by ward assignment (primary wards housing patients with tuberculosis [medical and HIV wards] compared with wards infrequently housing patients with tuberculosis). Health care workers with direct patient contact included physicians, nurses, nursing aides, respiratory therapists, and social workers; workers without direct patient contact included administrative staff, clerks, dieticians, housekeepers, engineers, and laboratory personnel. Health care workers with tuberculin skin-test conversions or active tuberculosis or both were identified by reviewing employee health and infection control records during the study period. Data collected included age, sex, race, history of bacille CalmetteGurin (BCG) vaccination or tuberculosis exposure or both, country of origin, job title, duration of employment, and work location at time of tuberculin skin-test conversion. Statistical Analysis Data were collected on standardized forms, entered into Epi Info Version 5.01b software, and analyzed [17]. Categorical variables were compared by the Fisher exact or chi-square test, and relative risks (RRs) were calculated. Continuous variables were compared by the Student t-test or the Kruskal-Wallis rank-sum test. Results Case-Patients Forty patients met the case definition (Figure 1). Case-patients in the preintervention and intervention periods were similar in age, race, sex, HIV serologic status, and diagnosis of AIDS (data not shown). However, case-patient mortality decreased in the intervention compared with the preintervention period (4 of 10 [40%] compared with 25 of 30 [83%] deaths; P = 0.01). Further, in the preintervention period, 20 of 25 (80%) case-patient deaths were attributed to tuberculosis, whereas in the intervention period, only