Delays in the Suspicion and Treatment of Tuberculosis among Hospitalized Patients

One of the factors cited as contributing to the recent resurgence of tuberculosis is a decline in expertise in the treatment of tuberculosis among physicians trained in the postsanitarium era. At least three studies have shown that management errors are common and may contribute to the emergence of drug resistance (1-3). Nosocomial transmission from unsuspected cases of tuberculosis has resulted in rapid propagation of highly resistant strains of Mycobacterium tuberculosis (4-6). Improvement of the general competence of physicians in the care of patients with known or suspected tuberculosis has been an important strategy for reestablishing control of tuberculosis in the United States (7-9). Along with diagnostic and treatment guidelines, specific recommendations have been outlined for prevention of nosocomial transmission in hospitals and other health care institutions (10). Maintenance of a high index of suspicion by clinicians, rapid institution of respiratory isolation, and early initiation of effective therapy are among the key principles of tuberculosis control (7, 9). Several studies have nevertheless suggested that delays in suspicion and treatment of tuberculosis are common among both hospitalized patients and those who visit outpatient clinics (11-13). These delays have been attributed to subtle or unusual disease presentations (12, 14, 15). Subsequent investigations have attempted to identify predictors of tuberculous disease as a means of shortening the interval between patient presentation and diagnosis (16, 17). However, few studies have systematically examined other delays, such as the time from initial suspicion of disease to initiation of therapy, that occur in the management of patients with tuberculosis. We describe the occurrence and patterns of various delays in the management of tuberculosis in our health system between 1988 and 1996. Methods Study Setting and Patients The study was conducted at the Barnes-Jewish-Christian (BJC) Health System, a university-affiliated network that provides medical care to patients from St. Louis and the surrounding regions of central and southern Missouri and southern Illinois. The specific hospitals enrolling patients in this investigation were Barnes-Jewish (a 1500-bed urban teaching hospital affiliated with Washington University School of Medicine), Christian Northeast (475 beds), Christian Northwest (229 beds), Missouri Baptist (500 beds), Boone (344 beds), Alton Memorial (222 beds), Parkland (133 beds), and Barnes-Jewish-St. Peters (111 beds). All patients admitted to the BJC Health System from January 1988 to December 1996 were eligible for inclusion in this investigation. All patients older than 15 years of age with a positive culture for Mycobacterium tuberculosis were entered into the study database. The study was approved by the Washington University School of Medicine Human Studies Committee. Study Design and Data Collection We used a retrospective cohort design that segregated hospitalized patients with tuberculosis according to whether or not the initial suspicion or treatment of tuberculosis had been delayed. An infection control nurse reviewed the inpatient and outpatient medical and health department records of each patient by using a standardized data collection tool. In addition, telephone follow-up was performed for all patients with working telephones. Outcome variables were mortality, duration of hospitalization, administration of antituberculous therapy, and delays in the diagnosis and treatment of tuberculous disease. Standard risk factors, as defined by the American Thoracic Society and the Centers for Disease Control and Prevention (8), for tuberculous infection and for development of tuberculous disease after infection were sought from the medical record. The following presenting signs and symptoms at the time of hospitalization were recorded: cough present for at least 4 weeks, fever, night sweats, weight loss, hemoptysis, dyspnea, chest pain, fatigue, weakness, and anorexia. The presence of peripheral lymphadenopathy that was palpable on the physical examination was noted along with the findings from chest radiography done at hospital admission. The type of tuberculous disease was recorded by using the following descriptors: pulmonary, extrapulmonary, smear-positive sputum, cavitary, miliary, and meningeal. Extrapulmonary tuberculosis was defined as disease in organs other than the lungs (including pleurisy but not mediastinal lymphadenopathy) (18). Miliary disease was defined by using standard criteria (19). Mortality was defined as death from any cause within 12 months (360 days) from the date of initial hospital admission. Samples for mycobacterial smears and cultures were processed, stained, and cultured according to standard procedures (20). Three time intervals were calculated by using dates obtained from review of medical and public health records. The overall management interval was defined as the time from admission to initiation of antituberculous chemotherapy. The suspicion interval was defined as the time from admission to the first suspicion of tuberculosis, and the treatment interval was the time from the first suspicion of disease to initiation of treatment. Intervals that exceeded 24 hours were considered indicative of a delay. Suspicion of tuberculosis required either an order for respiratory isolation or submission of specimens for acid-fast smear or culture. Mortality during the follow-up period was determined by using a combined review of the medical and health department records and telephone follow-up and was confirmed by using the death certificate registry of Missouri and records of the U.S. Social Security Administration. For the past 3 years, the infection control department of Barnes-Jewish Hospital, the largest institution in the BJC Health System, has maintained a database describing employees who sustained a workplace exposure to patients with tuberculosis. From this database, we extracted the numbers of employees with documented exposures for each patient with tuberculosis who was not efficiently isolated and treated. Statistical Analysis All comparisons were unpaired, and all tests of significance were two-tailed. Continuous variables were compared by using the Student t-test for normally distributed variables and the Wilcoxon rank-sum test for non-normally distributed variables. The chi-square test and the Fisher exact test were used to compare categorical variables. The primary data analysis compared patients who experienced an overall management delay with those who had not experienced such delays. Relative risks, odds ratios, and their 95% CIs were calculated by using standard methods (21). All values are expressed as the median SD (continuous variables) or as a percentage of the group from which they were derived (categorical variables), along with fifth and ninety-fifth percentiles. A P value of 0.05 or less was considered statistically significant. Kaplan-Meier curves were used to analyze patient survival. Multiple logistic regression analysis, done by using a commercial statistical package (22), was used to identify predictor variables that were significantly related to the likelihood of having an overall management delay during the period of observation (that is, overall management delay was the dependent outcome variable). Baseline covariates were included in models that were judged a priori to be clinically sound. This was prospectively determined to be necessary to avoid producing spuriously significant results with multiple comparisons (23). Potential predictor variables for model entry were identified by using univariate analysis, in which a P value of 0.15 was used to determine entry into the logistic regression model. Results of the logistic regression analysis are reported as adjusted odds ratios with 95% CIs. Results Culture-positive tuberculosis was diagnosed in 203 patients hospitalized in the BJC Health System. Patients ranged in age from 16 to 95 years (mean, 58.0 21.4 years); 55.2% were men and 44.8% were women. Demographic characteristics, risk factors for tuberculous infection, and characteristics of disease presentation are shown in Table 1. Table 1. Demographic Characteristics, Risk Factors for Tuberculosis, and Disease Presentation Overall Management Delay The median interval from hospital admission to initiation of antituberculous chemotherapy (overall management interval) was 6 days (5th and 95th percentiles, 1 and 52 days). An overall delay in management (overall management interval longer than 24 hours) occurred in 152 patients (74.9% [95% CI, 68.9% to 80.9%]) (Figure 1). An overall delay of more than 10 days occurred in 68 patients (33.5% [CI, 27.0% to 40.0%]), and an overall delay of more than 25 days was seen in 38 patients (18.7% [CI, 13.3% to 24.1%]) (Figure 2). No significant differences in the likelihood of an overall management delay (P>0.2), suspicion delay (P>0.2), or treatment delay (P>0.2) were found among patients admitted to a tertiary-level, university-affiliated medical center compared with patients who received care in community hospitals. Figure 1. Percentage of patients with delays in diagnosis and treatment of culture-proven tuberculosis. Figure 2. Distribution of overall delays for the study cohort. Univariate analysis identified demographic factors and disease characteristics that were significantly associated with an overall management delay (Table 1). Multiple logistic regression analysis that controlled for sex, age, ethnicity, and other potential risk factors for overall management delay as identified by the univariate analysis showed that absence of cavitary infiltrates, absence of meningeal disease, absence of hemoptysis, and smear-negative sputum were independently associated with overall management delay (Table 2). No significant relation was found between the presence or absence of an overall management delay and 1-year mortality (P>0.