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Epidemiologic Notes and Reports Nosocomial Transmission of Multidrug-Resistant Tuberculosis to Health-Care Workers and HIV-Infected Patients in an Urban Hospital -- Florida

From January through April 1990, tuberculin skin-test conversions* occurred among eight health-care workers (HCWs) on a specialized ward for human immuno deficiency virus (HIV)-infected patients at a large urban hospital in Florida. In February 1990, hospital personnel initiated an investigation of possible nosocomial transmission of tuberculosis (TB) at the hospital. In May, the hospital laboratory reported that the number of isolates of Mycobacterium tuberculosis resistant to multiple anti-TB drugs had increased during 1989 (Figure 1). This report provides preliminary findings from the ongoing investigation of possible nosocomial transmission of multidrug-resistant TB (MDR-TB) at the hospital. The investigation is being conducted by the hospital, the local health department, the Florida Department of Health and Rehabilitative Services, and CDC.

A case of MDR-TB was defined as a positive culture for M. tuberculosis in any patient at the hospital from January 1, 1988, through January 31, 1990, whose clinical course was consistent with TB and whose isolate was resistant to at least isoniazid (INH) and rifampin. Drug-resistant isolates were identified by review of microbiology records at the hospital and at the state mycobacteriology laboratory. Twenty-nine cases were identified, of which 22 (76%) were diagnosed between June 1, 1989, and January 31, 1990. Nine (31%) of the 29 case-patients had medical-record evidence of prior TB or a positive tuberculin skin test.

To identify risk factors for MDR-TB, a case-control study was conducted by comparing case-patients with randomly selected TB patients at the hospital with drug-susceptible M. tuberculosis isolates. Case-patients were more likely to have HIV infection or acquired immunodeficiency syndrome than control-patients (27/29 vs. 16/28; odds ratio (OR)=10.1; 95% confidence interval (CI)=1.8-100.4).

A second case-control study compared case-patients with randomly selected patients at the hospital who had both HIV infection and TB with drug-susceptible M. tuberculosis isolates. This study found that case-patients were more likely to have had opportunistic infections (e.g., Pneumocystis carinii pneumonia) before their TB diagnosis (18/29 vs. 3/29; OR=14.2; 95% CI=3.1-85.7) and less likely to respond clinically to anti-TB therapy (4/27 vs. 21/24; OR=0.02; 95% CI=0.0-0.2). Before onset of TB, case-patients were more likely to have attended the HIV clinic on the same day as and/or to have been hospitalized on the HIV ward at the same time as a case-patient with acid-fast bacilli (AFB)-smear--positive sputum (14/29 vs. 1/29; OR=26.1; 95% CI=3.2-1143.2). Two case-patients who did not have hospital exposure were household contacts of another case-patient. Compared with controls, case-patients were hospitalized and/or in the HIV clinic more days while sputum AFB-smear-positive (mean: 23 vs. 7 days, p=0.002). There were no statistically significant differences between case- and control-patients in sex, age, race, or HIV transmission category.

From January 1988 through July 1990, 10 (36%) of 28 HIV-ward HCWs had documented skin-test conversions (27 conversions per 100 person years); in the HIV clinic, three (25%) of 12 susceptible HCWs had documented skin-test conversions (16 per 100 person years). In contrast, on a thoracic surgery ward where patients with TB were rarely admitted, none of 15 susceptible HCWs had skin-test conversions during the same period. The probable periods of exposure for the 10 HCW converters on the HIV ward coincided with the periods that case-patients who were sputum AFB-smear-positive were hospitalized on that ward.

Infection-control policy on the HIV ward required that patients with any pulmonary symptoms and/or abnormal chest radiographs be routinely placed in TB isolation (AFB isolation) until TB was excluded or until they had been on anti-TB therapy for at least 7 days. For some patients who presented with nonpulmonary complaints, TB was not initially suspected, and they were not placed in AFB isolation. Patients with TB who were on anti-TB drugs were not routinely placed in isolation on readmission; however, some of these patients were later recognized to have AFB-smear-positive MDR-TB.

Hospital personnel reported that, on the HIV ward, doors of AFB isolation rooms were sometimes left open, and HCWs and visitors entering the rooms sometimes used masks improperly. Patients in isolation were sometimes allowed to leave their rooms if they wore masks; however, patients sometimes removed masks for short periods while out of their rooms. Aerosolized pentamidine treatments and diagnostic sputum inductions were performed at the bedside. All 24 rooms on the HIV ward were used for AFB isolation. Testing of 23 of these rooms with smoke tubes indicated that six had positive pressure relative to the hallway.

Patients with TB (including some subsequently reported to have MDR-TB) received follow-up care, including aerosolized pentamidine administration and sputum inductions, at the HIV clinic. Based on tests using smoke tubes, the pentamidine rooms had positive pressure relative to the central treatment area, which, in turn, had positive pressure relative to the adjacent waiting area. The engineering diagrams indicated that air from the sputum induction room was recirculated into other areas of the HIV clinic.

Primary isolation and identification of M. tuberculosis was performed at the hospital's mycobacteriology laboratory. Isolates were then sent to the state mycobacteriology laboratory for drug-susceptibility testing. Because of the time required for completion and verification of susceptibility testing, results were not available to clinicians for at least 8 weeks after specimen collection. Reported by: R Uttamchandani, MD, R Reyes, MD, S Dittes, MD, T Cleary, PhD, A Pitchenik, MD, M Fischl, MD, Univ of Miami; J Otten, A Breeden, C Hilsenbeck, PhD, Jackson Memorial Hospital; J Burr, MD, Dade County Public Health Unit; J Simmons, MD, District 11, W Bigler, PhD, H Valdez, R Cacciatore, J Witte, MD, RA Calder, MD, State Epidemiologist, Florida Dept of Health and Rehabilitative Svcs. Hospital Infections Program, Center for Infectious Diseases; Div of Tuberculosis Control, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: Although airborne transmission of M. tuberculosis in health-care settings has been described (1-4), this appears to be the first documentation of nosocomial transmission of drug-resistant TB. The clinical and epidemiologic findings in this investigation suggest that most MDR-TB cases were newly acquired tuberculous infection rather than reactivation of latent infection. In addition, the findings indicate transmission of infection to household contacts and, possibly, to HCWs.

Factors that may have contributed to this outbreak included 1) delays in adequate treatment of MDR-TB because of the length of time required to perform and verify drug-susceptibility tests; 2) prolonged periods of infectiousness in patients whose cure was delayed by MDR-TB; 3) inadequate duration of, and occasional lapses in, AFB isolation precautions on the HIV ward; 4) delays in recognition of TB in some patients (5); 5) presence of MDR-TB patients in the HIV clinic while still infectious because of delayed recognition of drug resistance; and 6) improperly balanced ventilation in the HIV ward and clinic.

To reduce the risk for nosocomial TB transmission, patients with suspected or confirmed TB should be placed in AFB isolation and started on effective anti-TB therapy. While hospitalized, they should remain in AFB isolation until clinically improved with substantial reduction in cough and until the number of organisms on sequential sputum AFB smears is decreasing (6,7; CDC, unpublished data**). Determination of infectiousness should be based on assessment of both clinical and bacteriologic response to therapy (6,7; CDC, unpublished data). Patients who are likely to be infected with drug-resistant organisms should remain in AFB isolation until AFB smears are negative (6; CDC, unpublished data). Patients with infectious TB should not be discharged to homes with immunocompromised persons or to community group settings (e.g., correctional facilities, nursing homes, hospices, or other organized group homes) unless AFB precautions can be provided. After patients are discharged, they should be followed with serial sputum AFB smears to verify continued bacteriologic response to therapy. When TB patients return for follow-up care, provisions should be made to prevent TB transmission in the outpatient setting (CDC, unpublished data).

Initial M. tuberculosis isolates from all patients should be tested for drug susceptibility. Radiometric techniques may reduce the time required for culture and drug- susceptibility testing (8). All drug-resistant isolates should be reported to care providers rapidly so that adequate therapy can be ensured. All patients with drug-resistant TB and all patients at high risk for noncompliance should be placed on directly observed therapy.

Ventilation in AFB isolation rooms and other areas of health-care facilities should be designed and maintained according to published guidelines (6; CDC, unpublished data). Ideally, sputum induction and aerosolized pentamidine treatments should be administered only in single-patient rooms or booths that have negative pressure relative to adjacent areas and are exhausted directly outside (9). Direction of air flow in patient isolation rooms, sputum induction rooms, and pentamidine rooms or booths should be frequently monitored. All HCWs, including nonpatient-care workers and volunteers, who have potential exposure to TB should participate in an organized TB skin-testing program to identify infected HCWs who may be candidates for preventive therapy and to monitor the effectiveness of infection-control practices (10; CDC, unpublished data).

This outbreak was characterized by M. tuberculosis isolates resistant to the two first-choice anti-TB drugs, INH and rifampin. Outbreaks of MDR-TB can be difficult and expensive to control and are typically associated with prolonged morbidity and increased mortality (11,12). Management of drug-resistant TB patients and their contacts is complex and needs to be individualized with consideration of multiple factors, including their immunologic status.

The extent of this problem nationally is not known because surveillance for M. tuberculosis drug resistance is not routinely conducted. To better characterize the problem, health departments should consider establishing surveillance for drug-resistant M. tuberculosis. Outbreaks of drug-resistant TB should be reported through state health departments to CDC's Division of Tuberculosis Control, Center for Prevention Services (telephone (404) 639-2519), to help determine the extent of this problem, identify risk factors, and develop and implement control measures.

References

  1. Brennen C, Muder RR, Muraca PW. Occult endemic tuberculosis

in a chronic care facility. Infect Control Hosp Epidemiol 1988;9:548-52.

2. Catanzaro A. Nosocomial tuberculosis. Am Rev Respir Dis 1982;125:559-62.

3. Ehrenkranz NJ, Kicklighter JL. Tuberculosis outbreak in a general hospital: evidence of airborne spread of infection. Arch Intern Med 1972;77:377-82.

4. Haley CE, McDonald RC, Rossi L, et al. Tuberculosis epidemic among hospital personnel. Infect Control Hosp Epidemiol 1989;10:204-10.

5. Kantor HS, Poblete R, Pusateri SL. Nosocomial transmission of tuberculosis from unsuspected disease. Am J Med 1988;84:833-8.

6. Garner JS, Simmons BP. Guideline for isolation precautions in hospitals. Infect Control 1983;4(suppl):245-325.

7. CDC. Guidelines for prevention of TB transmission in hospitals. Atlanta: US Department of Health and Human Services, Public Health Service, 1982; DHHS publication no. (CDC)82-8371.

8. Saddiqi S, Libonati J, Middlebrook G. Evaluation of a rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol 1981;13:908-12.

9. CDC. Mycobacterium tuberculosis transmission in a health clinic--Florida, 1988. MMWR 1989;38:256--8,263-4. 10. Williams WW. Guidelines for infection control in hospital personnel. Infect Control 1983;4(suppl):326-49. 11. CDC. Outbreak of multidrug-resistant tuberculosis--Texas, California, and Pennsylvania. MMWR 1990;39:369-72. 12. CDC. Drug-resistant tuberculosis--Mississippi. MMWR 1977;26:417-8,423.

  • Reaction of greater than or equal to 10 mm to a Mantoux skin test using 5 tuberculin units of purified protein derivative in a person who previously had no reaction.

** Updated guidelines for preventing transmission of TB in health-care settings where persons with HIV infections receive care are in preparation as an MMWR Recommendations and Reports.

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