The emergence of multidrug-resistant tuberculosis (MDR-TB) as a major health problem over the past several years has prompted the Centers for Disease Control and Prevention (CDC) to closely reexamine tuberculosis policy in the United States. A series of guidelines have been issued by the CDC since 1991 concerning MDR-TB in the United States. The following statement on MDR-TB is extracted from CDC's "National Action Plan To Combat Multidrug-Resistant Tuberculosis" (p.7).
Recently, drug-resistant TB has become a serious concern. In a recent survey in New York City, 33 percent of cases had organisms resistant to at least one drug, and 19 percent had organisms resistant to both isoniazid and rifampin, the two most effective drugs available for treating TB. When organisms are resistant to both isoniazid and rifampin, the course of treatment increases from 6 months to 18-24 months, and the cure rate decreases from nearly 100 percent to less than 60 percent.
Drug-resistant TB is not limited to New York. CDC recently conducted a nationwide survey of drug resistance among all TB cases provisionally reported during the first3 months of 1991. Overall, 14.4 percent of these cases tested had organisms resistant to at least one antituberculosis drug, and 3.3 percent had organisms resistant to both isoniazid and rifampin. Furthermore, the drug resistance problem appears to be worsening. For example, from 1982 to 1986, only 0.5 percent of new cases were resistant to both isoniazid and rifampin; by 1991, this proportion had increased to about 3.1 percent. Among recurrent cases, 3.0 percent were resistant to both drugs during 1982-1986, but in 1991 this proportion had more than doubled, to 6.9 percent.
Against this background of increasing numbers of TB cases and increasing numbers of drug-resistant cases, a serious new phenomenon has appeared: outbreaks of multidrug-resistant (MDR) TB in institutional settings. From 1990 through early 1992, CDC, in collaboration with State and local health departments, investigated seven outbreaks of MDR-TB in hospitals and correctional facilities in Florida and New York. To date, these outbreaks have included more than 200 MDR cases. Virtually all these cases had organisms resistant to both isoniazid and rifampin, and some had organisms resistant to seven antituberculosis drugs. Most of the patients in these outbreaks were infected with HIV. Mortality among patients with MDR-TB in these outbreaks was high, ranging from 72 percent to 89 percent, and the median interval between TB diagnosis and death was short, from 4 to 16 weeks. In addition to hospitalized patients and inmates, transmission of MDR-TB to health-care workers and prison guards has also been documented; at least nine of these workers have developed active MDR-TB, and five of them have died.
The rise in drug-resistant TB and the outbreaks of MDR-TB are a manifestation of serious underlying problems in the health-care infrastructure in the United States. An increasing proportion of TB cases is occurring among persons who were born in another country or who are homeless, who have substance abuse problems or mental illness, or who have other socioeconomic or medical problems, such as HIV infection, that make compliance with therapy difficult. Yet, at the same time that the number and complexity of TB cases have been increasing, fiscal constraints in government at all levels have led to cutbacks in many TB control programs. As a result, health departments have not had adequate resources to place all potentially noncompliant patients on directly observed therapy or to bring outbreaks under control. There have been shortages of antituberculosis drugs and significant increases in their costs. Screening and preventive therapy have not been offered consistently to many groups at high risk of TB (e.g., HIV-infected persons) because of limited resources.
The following are special considerations and recommendations for residential and nonresidential methadone and other drug treatment programs regarding MDR-TB.
In setting up a screening and treatment or referral program, the following medical components need to be included:
All patients entering drug treatment programs should be screened for TB at entry to the program and, especially in high TB incidence areas, should have a followup PPD skin test every 6 to 12 months.
All employees in methadone treatment and other drug treatment programs should have a PPD skin test every 6 to 12 months.
Any patient or employee who is exposed to a case of TB should have a TB skin test at the time of exposure and again 12 weeks later.
Careful consideration should be given to the question of whether or not hospitalization is appropriate for a person with MDR-TB. There are conditions under which a person with known or suspected MDR-TB does not need to be hospitalized.
If the person is medically stable and has a stable home situation in which young children or immunocompromised persons will not be exposed, and is on effective therapy with good clinical and bacteriologic regimens, hospitalization is not required. All therapy should be directly observed for anyone who is not hospitalized, and close medical followup is mandatory.
If the person is not medically stable and does not have an adequate home situation, hospitalization is appropriate.
To ensure compliance with TB therapy, all patients should be observed as they take their medications (for example, with the daily methadone dose).
Any patient being treated for MDR-TB or receiving prophylaxis for latent MDR-TB who is noncompliant with that treatment should be reported to the local health department and should not be allowed to enter the drug treatment facility.
Any patient in a methadone treatment program, whether residential or nonresidential, who develops any clinical signs or symptoms of TB must be immediately referred for medical treatment. In areas with MDR-TB, all such persons must be placed in respiratory isolation (that is, acid-fast bacilli isolation) in a hospital setting. Until the drug-susceptibility tests are available or until the AFB smear is negative (if initially the AFB smear was positive), the patient must remain in isolation. The person should be considered as potentially infectious until three sequential smears are negative for TB organisms.
Any patient in a residential facility who has a cough or other symptoms of possible TB should be removed from a dormitory-type setting to an infirmary or other isolated area until a medically qualified person has evaluated the patient for possible TB.
Programs should develop guidelines and procedures to decrease transmission of the TB bacillus by means of environmental precautions and appropriate ventilation measures. In any clinic area where patients are coughing, sneezing, or being asked to cough to give a sputum sample, the ventilation must be adequate. If adequate ventilation (negative pressure room with a minimum of six air exchanges per hour) is not available, these persons should not stay in the clinic area; clinics may need to have patients step outdoors and obtain sputum specimens from them there.
Both residential and nonresidential drug treatment facilities should consider installing and maintaining ultraviolet lights; use of such lights could play a role in killing the TB bacillus in certain areas of the treatment facility. CDC recommendations for ultraviolet light are in Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Settings (p. 15). The recommendations state in part:
The decision to use UV lamps should be made on a case-by-case basis. If UV lamps are used, applicable safety guidelines should be followed . . . UV lamps are not recommended for use in small rooms or booths where nebulizing devices will be used. UV units installed in ducts should not be used to recirculate air from a tuberculosis isolation room back into the general circulation.
All cases of active MDR-TB or cases of conversion to a positive skin test after exposure to MDR-TB should be reported to local/State health departments for followup. Close contact tracing, especially of household contacts including children, must be done promptly and properly.
The following persons should be evaluated for the presence of active MDR-TB as well as non-MDR-TB (that is, they should have a medical history/ physical examination, and chest x-ray):
With no evidence of active MDR-TB (after history/ physical examination and chest x-ray), the person requiring preventive therapy for MDR-TB may be placed on preventive therapy. Such therapy needs to be based on the drug-susceptibility testing of prior cases of MDR-TB in that geographic area. The correct preventive therapy after exposure to MDR-TB is not known.
Note: The proper preventive therapy for INH/RIF-resistant or additional drug-resistant TB is not INH alone. In some cases, for those who would normally require preventive treatment, the treatment of choice may be close medical followup rather than preventive therapy with multiple drugs.
For the HIV-infected, anergic person, again, the correct preventive therapy after known exposure to MDR-TB is not known. However, these persons should not only have close medical followup, but they should also be given prophylaxis based on discussion with local experts.
The appropriate drug combination for preventive treatment of MDR-TB must be determined by consulting with the local health department, the CDC, and others expert in treating TB. Table 1 defines the likelihood of exposure to MDR-TB. Figure 1 shows the CDC outline of the approach to use in selecting drug regimens for preventive therapy and for those at low to low-intermediate, and intermediate to high risk.
The duration of multidrug preventive therapy is 12 months for HIV-infected persons and at least6 months for others.
In general, close medical followup will be required for at least 2 years, regardless of whether patients are or are not given multidrug preventive therapy. Medical examinations and chest radiographs should be provided as follows:
For HIV-infected persons; every 3 months for 2 years
For HIV-negative, otherwise healthy persons; every 6 months for 2 years
All persons with presumed or documented MDR-TB should be placed in respiratory isolation in a hospital setting unless they are medically stable and the home situation is adequate, as discussed previously. Persons who are hospitalized should remain in strict respiratory isolation until three AFB smear-negative sputums, taken on three successive days, have been obtained. After three smear-negative sputums have been obtained, the person may be removed from respiratory isolation provided that no other signs or symptoms of ongoing pulmonary TB are present.
Persons with positive AFB sputum smears should be placed on directly observed anti-TB therapy pending the results of the sputum culture. For persons with positive AFB sputum smears or negative AFB sputum smears but presumed pulmonary tuberculosis, all anti-TB medications should be given as directly observed therapy pending the results of the sputum cultures. Likewise, for persons with presumed extrapulmonary tuberculosis with AFB positive or negative tissue smears, all therapy should be directly observed while culture results are awaited.
Following are recommendations for treatment of possible active MDR-TB while awaiting results of susceptibility testing. Consultation with a physician experienced in treating MDR-TB in the local area is advisable.
Prior to TB culture-susceptibility results, a minimum of a four- to five-drug anti-TB regimen should be initiated. There are currently no standard recommendations for the treatment of possible active MDR-TB while results of isolate susceptibility testing are being awaited. The initial treatment regimen will reflect the known susceptibility patterns of prior resistant isolates in that geographic region or, if known, of the contact case. Consultation with a physician experienced in treating MDR-TB in the local geographic area is necessary and is strongly advised.
The length of therapy has not been determined for infections caused by MDR-TB.
When drug-susceptibility results are available, the treatment regimen must be reevaluated and changed if needed.
For persons failing to respond to initial therapy, additional drugs may need to be added prior to obtaining the drug susceptibility results.
To ensure compliance with TB therapy, the patient should take the medication under supervised conditions, even in the hospital. Once the patient is discharged from the hospital, the medications must be taken in a supervised setting (for example, with the daily methadone dose). The pills should be swallowed in front of the person who dispenses the drugs to the patient.
Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues. Morbidity and Mortality Weekly Report 39(RR-17):1--29, 1990.
Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons - Florida and New York, 1988-1991. Morbidity and Mortality Weekly Report 40(34):585--591, Aug. 30, 1991.
Initial therapy for tuberculosis in the era of multidrug resistance. Recommendations of the Advisory Council for the Elimination of Tuberculosis. Morbidity and Mortality Weekly Report 42(RR-7):1--8, 1993.
Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients. Journal of the American Medical Association 267:2632--2634, 1992.
An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection. Annals of Internal Medicine 117:177--183, 1992.
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