Nosocomial Outbreaks Of Multidrug-resistant Tuberculosis Research Articles

Spread of Extensively Drug-resistant Tuberculosis

To the Editor: An emergency has been declared in KwaZulu Natal, South Africa, where an outbreak of 53 cases of a highly lethal form of tuberculosis (TB) has occurred (1,2). This outbreak was caused by an extensively drug-resistant TB (XDR TB) strain. XDR TB is defined as TB caused by Mycobacterium tuberculosis isolates resistant to isoniazid and rifampicin plus any fluoroquinolone and ≥1 of the 3 injectable second-line drugs (3). XDR TB may be considered an emerging disease but not a new disease. Nosocomial outbreaks of multidrug-resistant TB (MDR TB) occurred in Spain at the height of the HIV epidemic, when 49 TB cases were reported in an HIV ward in Madrid from 1991 through 1995 (4,5). Molecular epidemiology found that a particular strain caused 16 cases in another hospital in Madrid in 1993–1995 (6) and 31 cases in a hospital in Malaga in 1995–1998 (7,8). In total, 22 hospitals from 6 different regions of Spain were affected by this outbreak, which included at least 114 cases, caused by an M. bovis XDR strain (B strain) belonging to the M. tuberculosis complex. The patients included 1 from the Netherlands (8) and another from Canada (9). The strain responsible for the 1991–1995 outbreak in Spain fits the XDR TB case definition; it was resistant to the 5 first-line drugs, as well as to ofloxacin, aminosalicylic acid, cycloserine, ethionamide, capreomycin, amikacin, and clarithromycin. Isolates were tested for drug susceptibility by the Canetti method on Lowenstein-Jensen medium supplemented with isoniazid, rifampicin, ethambutol, streptomycin, amikacin, and pyrazinamide (6). The isolates were also tested on 7H10 Middlebrook agar for susceptibility to aminosalicylic acid, ethionamide, capreomycin, clarithromycin, and ofloxacin (6). No effective medical treatment was available for these patients. In 2 of the hospitals affected, all patients died, with a short survival time (median of 44 and 49.5 days for the 2 hospitals) between diagnosis and death (6,7). A high rate of reinfection (45%) also was noted among HIV-positive patients treated with anti-TB drugs (7). As a result of this outbreak, Spanish hospitals now implement exhaustive control measures, such as maintaining respiratory isolation units under negative pressure; in addition, a national surveillance network for MDR TB was set up in Spain in 1998. From 1998 through 2003, we detected 22 new cases of infection with this strain (10), but no new cases have since been reported to the national MDR TB database. Our experience indicates that the implementation of more stringent control measures and the use of new, more effective treatments for HIV infection can help to bring XDR TB outbreaks under control in developed countries. However, the outlook is bleak for developing countries like South Africa, in which coinfection with HIV and a highly transmissible and untreatable XDR TB strain could amplify the TB problem to levels unprecedented since the advent of antimicrobial drugs. These countries urgently require assistance with the establishment of control measures and the development of new drugs and effective vaccines against TB.

Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia.

A molecular epidemiologic study of 35 Mycobacterium tuberculosis isolates from 19 patients was conducted to define a nosocomial outbreak of multidrug-resistant tuberculosis in St. Petersburg, Russia. IS 6110-restriction fragment length polymorphism (RFLP) fingerprinting, together with investigations to detect mutations conferring drug resistance, revealed relationships between the isolates and links between the cases. Three patients and a nurse exposed to active tuberculosis were proved to be involved in the outbreak; the source case was identified. The outbreak strain possessed a 17-band RFLP pattern and a spoligoprofile (signals 35-43) characteristic of the W-Beijing family as well as distinctive mutations in katG315, rpoB531, embB306 and rpsL43. This specific RFLP pattern has previously been identified among Mycobacterium tuberculosis W-Beijing strains isolated across the former Soviet Union and in the St. Petersburg area of Russia. The spread of multidrug-resistant strains of W-Beijing genotype in the general population and in hospital settings presents a serious threat for public health in Russia. Specific pathogenic properties of W-Beijing genotype strains, such as enhanced transmissibility and the ability to cause reinfection and to readily acquire drug resistance to major antituberculosis drugs, along with special features of host response, have yet to be investigated.

High rate of tuberculosis reinfection during a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis strain B.

We present a study of a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis in 31 patients, 30 of whom were infected with human immunodeficiency virus; all 31 died of progressive tuberculosis. All M. bovis strains had identical spoligotyping patterns and showed resistance to 12 antituberculosis drugs. Reinfection was suggested in 11 cases and confirmed in 4 by molecular typing methods. The causative strain was named "B strain."

Delays in Tuberculosis Isolation and Suspicion Among Persons Hospitalized With HIV-Related Pneumonia

Despite awareness of HIV-related tuberculosis (TB), nosocomial outbreaks of multidrug-resistant TB among HIV-infected individuals occur. To investigate delays in TB isolation and suspicion among HIV-infected inpatients discharged with TB or Pneumocystis carinii pneumonia (PCP), common HIV-related pneumonias. Cohort study during 1995 to 1997. For PCP, 1,227 persons who received care at 44 New York City, Chicago, and Los Angeles hospitals. For TB, 89 patients who received care at five Chicago hospitals. Two-day rates of TB isolation/suspicion. For HIV-related PCP, Los Angeles hospitals had the lowest 2-day rates of isolation/suspicion of TB (24.3%/26.6% vs 65.5%/66.4% for New York City and 62.8%/58.3% for Chicago, respectively; p < 0.001 for overall comparison by chi(2) test for each outcome measure). Within cities, hospital isolation/suspicion rates varied from < 35 to > 70% (p < 0.001 for interhospital comparisons in each city). The Chicago hospital with a nosocomial outbreak of multidrug-resistant TB from 1994 to 1995 isolated 60% of HIV-infected individuals who were discharged with a diagnosis of HIV-related TB and 52% discharged with HIV-related PCP, rates that were among the lowest of all Chicago hospitals in both data sets. Low 2-day rates of TB isolation/suspicion among HIV-related PCP patients were frequent. One Chicago hospital with low 2-day rates of TB isolation/suspicion among persons with HIV-related PCP also had low 2-day rates of isolation/suspicion among confirmed TB patients. That hospital experienced a nosocomial multidrug-resistant TB outbreak. Educational efforts on the benefits of early TB suspicion/isolation among HIV-infected pneumonia patients are needed.

A continuing outbreak of multidrug-resistant tuberculosis, with transmission in a hospital nursery.

We investigated an increase in cases of multidrug-resistant tuberculosis (MDRTB) at a large urban facility where a prior nosocomial outbreak of MDRTB had occurred. Nosocomial transmission appeared to account for this outbreak as well, including a cluster of cases in a newborn nursery. Seven of 24 patients (29%) described in this investigation may have been exposed in the hospital nursery during an approximately 2-week period. We believe this to be the first documented outbreak of MDRTB in a hospital nursery. The transmission in the nursery demonstrates that the possibility of exposure to unrecognized active tuberculosis in nursery and hospital personnel is always present. Infection and active disease in the infants developed after a relatively short period of exposure. These findings underscore the need for adherence to published infection control guidelines in health care settings.

Occupational risk ofMycobacterium tuberculosis infection in hospital workers

We conducted a 4-year (1/89-12/92) retrospective cohort study among employees at a large metropolitan hospital where a nosocomial outbreak of multidrug-resistant tuberculosis (TB) had occurred. We compared the risk of tuberculin skin test (TST) conversion among employees who worked on wards where patients with culture-confirmed TB were cared for ("exposed") with the risk among employees who worked on wards with no such patients ("unexposed"). Exposed employees had a higher 4-year risk of TST conversion (14.5%) than unexposed employees (1.4%) (adjusted relative risk 13.4; 95 percent confidence interval 5.1-35.2). Exposed employees had significantly higher risks of conversion than unexposed employees during 1989-91, but not for 1992. Among the exposed, ward clerks had a risk of conversion (15.6%) only slightly lower than nurses (18.2%). We conclude that employees who worked in areas where patients with active M. tuberculosis infection were cared for, including workers who did not provide direct patient care, had a higher risk of TST conversion than employees who did not work in these areas. Reasons for the decline in risk over time include outbreak termination, fewer admissions of patients with TB, implementation of effective infection control measures, and possible resistance to infection in some members of the study population.

The emergence of drug-resistant tuberculosis in New York City.

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. 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. 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). 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

Concomitant with the resurgence of tuberculosis in the United States have been increasing reports of nosocomial transmission of TB. From January 1990 through September 1992, the Centers for Disease Control (CDC) investigated eight nosocomial outbreaks of multidrug-resistant tuberculosis (MDR-TB). Over 200 patients were infected; approximately 75% of these patients died. Risk factors for infection included human immunodeficiency virus infection or acquired immunodeficiency syndrome and recent hospitalization on the same ward as other MDR-TB patients. Restriction fragment length polymorphism (RFLP) analysis of M. tuberculosis isolates revealed unique strains were transmitted in each hospital. In three hospitals, health care workers (HCW) assigned to wards with MDR-TB patients were shown to be more likely to have tuberculin skin test (TST) conversions than HCW assigned to wards without MDR-TB patients. These outbreaks demonstrate the serious morbidity and mortality associated with nosocomial MDR-TB and emphasize the importance of adhering to current CDC guidelines for preventing the transmission of tuberculosis in healthcare settings, with special focus on HIV-related issues.

A nosocomial outbreak of multidrug-resistant tuberculosis (TB) among AIDS patients: Epidemiologic investigation and restriction fragment length polymorphism (RFLP)

A nosocomial outbreak of multidrug-resistant tuberculosis (TB) among AIDS patients: Epidemiologic investigation and restriction fragment length polymorphism (RFLP)