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Multidrug-Resistant Tuberculosis Outbreak on an HIV Ward -- Madrid, Spain, 1991-1995

Beginning in 1990, outbreaks of multidrug-resistant tuberculosis (MDR-TB) have been reported in hospitals and prisons in the eastern United States (1). During June 1991-January 1995, MDR-TB was diagnosed in 47 patients and one health-care worker at a 120-bed, infectious disease referral hospital in urban Madrid; on April 19, 1995, the Spanish Field Epidemiology Training Program was asked to investigate this outbreak. This report summarizes the findings of this investigation, which suggested that nosocomial transmission of MDR-TB occurred on a hospital ward for patients with human immunodeficiency virus (HIV) infection.

A case of MDR-TB was defined as culture-confirmed TB that was resistant to at least rifampin and isoniazid in a patient hospitalized on the ward for HIV-infected persons during June 1991-January 1995 and with no previous history of TB treatment. Case finding was coordinated by the mycobacteriology laboratory director and an infectious disease specialist, who reviewed medical records and laboratory results for persons with suspected MDR-TB. In addition to drug-susceptibility testing, analysis of resistant strains included DNA fingerprinting with restriction fragment-length polymorphism (RFLP). Because the hospital did not have in place a ventilation system that recirculated or removed air, the acid-fast bacilli (AFB) isolation capacity (negative pressure and number of air interchanges per hour) could not be assessed on the HIV ward.

MDR-TB was identified in 47 HIV-positive patients who had been hospitalized on the HIV ward during June 1991-January 1995. The mean age of case-patients was 34 years (range: 25-54 years); 39 (81%) were male, and 32 (67%) were injecting-drug users. The one health-care worker was HIV-positive and had worked on the HIV ward during 1990-1994. A total of 47 (98%) patients, including the health-care worker, had died at the time of the investigation; the mean interval from diagnosis of MDR-TB to death was 78 days. An analysis of isolates from TB cases throughout the hospital during 1991-June 1995 identified 104 that were drug-susceptible; 12 that were resistant to one drug; and 66 that were resistant to isoniazid, streptomycin, ethambutol, and rifampin (HSER) (Figure_1). The proportion of Mycobacterium tuberculosis strains identified that were MDR-TB increased from 10% in 1991 to 53% in 1993 to 65% in June 1995.

Beginning in 1993, the resistance pattern identified consistently in isolates was HSER: of the 26 cases diagnosed during October 1993-June 1995, this pattern was present in 24 (92%). Of the 12 isolates available for DNA fingerprinting, the same band patterns were present in 11 (Figure_2). For comparison, TB isolates were obtained from the two patients with different antibiograms; their RFLP analyses were distinct from those of isolates from the other patients.

A case-control study was conducted to identify potential risk factors for MDR-TB among HIV-infected patients who had been hospitalized on the HIV ward during September 15, 1991-December 31, 1994, and in whom TB was diagnosed in 1994. Cases included patients with isolates with the HSER resistance pattern (n=18); controls were patients with isolates sensitive to rifampin, isoniazid, streptomycin, and ethambutol (n=17). The category "potentially infective" for TB patients was defined as the period from 2 weeks before a positive sputum smear or TB culture confirmation until sputum cultures were negative or until death. "Possibly exposed" for patients without TB was defined as hospitalization on the HIV ward concurrent with the hospitalization of a potentially infectious patient during the period until 2 weeks before TB was diagnosed in the potentially infectious patient. Case- and control-patients were similar in age, sex, HIV risk group, interval of time between HIV diagnosis and TB diagnosis, and CD4+ T-lymphocyte count at the time of TB diagnosis. However, before the hospitalization during which MDR-TB was diagnosed, 13 (72%) of the case-patients had been hospitalized on the HIV ward, compared with five (29%) control patients (odds ratio=6.2; 95% confidence interval=1.2-36.7). Of all patients with TB diagnosed in 1994 who were hospitalized on the HIV ward, 5% had MDR-TB. Case patients were more likely to have been possibly exposed to potentially infective wardmates and to have more days of exposure (13 {72%} for a median of 26 days) than control patients (seven {41%} for a median of 8 days) (for duration of exposure, chi square for linear trend=7.0; p=0.03).

Reported by: D Herrera, R Cano, P Godoy, EF Peiro, J Castell, C Ibanez, F Martinez Navarro, Field Epidemiology Training Program; V Moreno, A Ortega, L Sanchez, R Duran, F Pozo, Carlos III Health Institute, Ministry of Health and Consumer Affairs, Spain. Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; International Br, Div of Field Epidemiology, Epidemiology Program Office, CDC.

Editorial Note

Editorial Note: The findings in this report document the first outbreak of nosocomial MDR-TB to be investigated in Spain. Characteristics of this outbreak that are similar to previously reported outbreaks include MDR-TB among patients hospitalized in an HIV-dedicated ward, a high death rate within 3 months of onset, and the role of mycobacteriology laboratory-based surveillance in recognizing similar resistance patterns with confirmation through RFLP fingerprinting (2).

Measures to control this outbreak have included 1) isolating all MDR-TB patients in a separate area of the hospital and the on-site provision of all clinical and diagnostic services; 2) notifying family, community members, and wardmates of patients whose MDR-TB had been diagnosed during January-June 1995 about their exposure, scheduling follow-up evaluation, and offering isoniazid preventive therapy (although isoniazid resistance had been identified in isolates from the outbreak, this resistance was low); 3) informing all hospital staff about the outbreak, and establishing a TB screening clinic that was attended by 565 (96%) of 591 employees; 4) purchasing personal respiratory protection devices that fulfilled recommended sealage and filtering criteria (3) and distributing these devices to staff exposed to TB patients; and 5) developing plans to improve the capacity of the hospital's mycobacteriology laboratory and to install 11 AFB isolation rooms.

To prevent nosocomial transmission of M. tuberculosis, hospital staff should monitor surveillance for and rapidly diagnose, isolate, and treat persons with suspected TB and ensure timely laboratory confirmation with identification of drug-susceptibility patterns. Because immunocompromised persons, such as those on HIV wards, are at increased risk for TB, surveillance and rapid confirmation are especially important to prevent M. tuberculosis transmission. In addition, hospitals and other health-care facilities should conduct regular employee TB screening clinics (graded by occupational risk category) that closely monitor tuberculin skin test conversions; such clinics can assist in surveillance for nosocomial transmission of TB.


  1. Kent JH. The epidemiology of multidrug-resistant tuberculosis in the United States. Med Clin North Am 1993;77:1391-409.

  2. CDC. Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons -- Florida and New York, 1988-1991. MMWR 1991;40: 585-91.

  3. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities, 1994. MMWR 1994;43(no. RR-13).


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