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Multidrug-Resistant Tuberculosis, 1994
Patricia M. Simone, MD, and Samuel W. Dooley, MD
Drug-resistant tuberculosis is not a new phenomenon: resistance
to antituberculosis drugs has been noted since the drugs were first
introduced, and occasionally outbreaks of drug-resistant tuberculosis
have been reported. But recent outbreaks of multidrug-resistant
tuberculosis have differed considerably from the previous outbreaks.
This article will review the causes, the treatment, and the control
of drug-resistant tuberculosis and describe the recent outbreaks
of multidrug-resistant tuberculosis.
Tuberculosis has afflicted humans since ancient times. Tuberculous
lesions have been found in Egyptian mummies, and the disease was
well described by Hippocrates. During the Industrial Revolution,
substantial increases in tuberculosis accompanied urban crowding
and malnutrition. In the 19th century, an estimated one quarter
of the adult population of Europe died of tuberculosis.
In the United States, approximately 20% of deaths in the early
1800s were attributed to tuberculosis; this figure had decreased
to 11% by midcentury. Mortality declined throughout the century
probably because of improvements in living conditions and nutrition.
The realization in the late 1800s that tuberculosis was infectious
eventually led to the isolation of tuberculosis patients in treatment
centers, or sanatoria. Treatment in sanatoria consisted of bed rest,
enhanced nutrition, and various surgical procedures aimed at closing
lung cavities. The discovery of antituberculosis medications in
the mid20th century further reduced tuberculosis incidence
and mortality and rendered surgical resection unnecessary.
Soon after antituberculosis medications were introduced, researchers
recognized that tuberculosis was unique with respect to the frequency
and importance of the emergence of drug resistance during therapy.
They discovered that drug-resistant mutants existed in wild strains
of Mycobacterium tuberculosis, that selection of these mutants
could occur under certain treatment conditions, and that drug-resistant
tuberculosis was more difficult to cure. Once additional drugs were
available, controlled trials were conducted and demonstrated that
combined regimens were more efficient than single-drug regimens
in treating tuberculosis and preventing the emergence of drug resistance.
Transmission and Pathogenesis of Drug-Resistant Tuberculosis
Drug-resistant and drug-susceptible tuberculosis are transmitted
in the same way. For many years, drug-resistant tuberculosis was
believed to be less infectious than drug-susceptible tuberculosis.
This belief was largely based on animal studies that showed that
isoniazid-resistant bacilli were less virulent than isoniazid-susceptible
bacilli. Reports of outbreaks of drug-resistant tuberculosis in
the 1970s and 1980s did not completely dispel this notion. In 1985
Snider and colleagues compared the risk of infection among persons
exposed to drug-resistant bacilli with the risk among persons exposed
to drug-susceptible bacilli (1).
They found no evidence that drug-resistant bacilli were less infectious
than drug-susceptible bacilli. In fact, contacts of previously untreated
patients had a similar risk of infection, regardless of whether
the bacilli were drug-resistant or drug-susceptible. They did find,
however, an increased risk of infection in contacts of patients
with drug-resistant tuberculosis who had been previously treated.
They suggested that the increased risk resulted from prolonged exposure
rather than increased infectiousness of the drug-resistant bacilli.
Patients with drug-resistant tuberculosis who have a history of
prior treatment are more likely to have been nonadherent to therapy
and infectious for longer periods of time than patients with drug-susceptible
tuberculosis. The recent outbreaks of multidrug-resistant tuberculosis
support these findings that drug-resistant tuberculosis is no less
infectious than drug-susceptible tuberculosis and that, in fact,
prolonged periods of infectiousness may facilitate transmission.
Drug-resistant tuberculosis occurs when drug-resistant bacilli
outgrow drug-susceptible bacilli. The drug-resistant organisms are
produced by random mutations in the bacterial chromosome which occur
spontaneously in wild-type strains even before the strains come
in contact with an antituberculosis drug (2).
Mutations can produce bacilli resistant to any of the antituberculosis
drugs, although they occur more frequently for some drugs than others.
The average mutation rate in M. tuberculosis for resistance
to isoniazid is 2.56 x 10-8 mutations per bacterium per
generation; for rifampin, 2.25 x 10-10; for ethambutol,
1.0 x 10-7; and for streptomycin, 2.95 x 10-8.
The mutation rate for resistance to more than one drug is calculated
by multiplying the rates for the individual drugs. For example,
the mutation rate for resistance to both isoniazid and rifampin
is approximately 2.56 x 10-8 times 2.25 x 10-10,
or 5.76 x 10-18. The expected ratio of resistant bacilli
to susceptible bacilli in an unselected population of M. tuberculosis
is about 1:106 each for isoniazid and streptomycin and
1:108 for rifampin. Mutants resistant to both isoniazid
and rifampin should occur less than once in a population of 1014
bacilli. Pulmonary cavities contain about 107 to 109
bacilli; thus, they are likely to contain a small number of bacilli
resistant to each of the antituberculosis drugs but unlikely to
contain bacilli resistant to two drugs simultaneously(3).
Drug-resistant mutants are selected when therapy is inadequate,
for example, when a single drug is used to treat a large population
of bacilli. The treatment of a wild-type strain of M. tuberculosis
with a single drug kills the majority of the bacilli in the population,
but the small number of mutants resistant to the drug continue to
multiply (Figure 1).
After 2 weeks to several months of treatment with the single drug,
the resistant bacilli will outgrow the susceptible bacilli, causing
clinical drug resistance. Furthermore, in a large population of
resistant mutants, additional mutations can occur resulting in doubly-resistant
mutants (Figure 2).
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Figures 1 and 2. Empty circles represent tubercle bacilli susceptible
to all antituberculosis drugs. A circle with a letter in it
represents a tubercle bacillus with resistance to the drug indicated
by the letter: I = isoniazid resistance; R = rifampin resistance;
P = pyrazinamide resistance. Adapted with permission from
Reichman LB: A looming public health nightmare. Lungs at Work
1992. Copyright © 1992 American Lung Association.
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In contrast, the emergence of drug resistance is far less likely
in most types of extrapulmonary tuberculosis, in which the bacillary
population is much smaller. The bacillary population is even smaller
in latent tuberculosis infection, so the chances that drug resistance
will emerge during preventive therapy are negligible.
Drug resistance is divided into two types: primary resistance and
secondary (or acquired) resistance. Primary resistance occurs in
persons who do not have a history of previous treatment; these persons
are initially infected with resistant organisms. Secondary resistance
occurs during therapy for tuberculosis, either because the patient
was treated with an inadequate regimen or because the patient did
not take the prescribed regimen appropriately. Treatment with two
or more drugs in combination can prevent the emergence of drug resistance,
if the regimen includes at least two drugs to which the organisms
demonstrate in vitro susceptibility.
Multidrug resistance is defined as in vitro resistance of
a strain of M. tuberculosis to two or more of the antituberculosis
drugs. Clinically, the most important pattern of multidrug resistance
is resistance to both isoniazid and rifampin. This combination has
been associated with an overall cure rate of less than 60% in some
reports, similar to the rate of cure before the discovery of antituberculosis
The two main causes of drug resistance are nonadherence to therapy
and the use of inadequate treatment regimens. When medications are
not taken as prescribed, the infecting bacilli may be exposed to
a single drug for long periods of time, which allows drug-resistant
organisms to emerge (Figure
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In addition, some regimens may contain multiple drugs but only
one drug to which the infecting bacilli are susceptible. This can
happen when primary drug resistance is not suspected or when a single
drug is added to a failing regimen (Figure
4). These regimens are equivalent to single-drug therapy,
and they can select multidrug-resistant organisms. Acquired multidrug
resistance usually results from a combination of nonadherence and
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Tuberculosis in the United States
Since nationwide reporting first began, the number of reported
tuberculosis cases declined by an average of 5.6% per year, from
more than 84,000 cases in 1953 to 22,255 cases in 1984. In 1985
this decline ended abruptly; from 1985 through 1993, the number
of cases increased by 14%. It is estimated that 64,000 more cases
have occurred since 1985 than would have been expected had the trend
of 1980 to 1984 continued (Figure
5) (6). The excess cases
have been attributed to a number of factors including the human
immunodeficiency virus (HIV) epidemic, tuberculosis occurring in
foreign-born persons from countries with a high prevalence of tuberculosis,
the transmission of tuberculosis in congregate settings (e.g., health
care facilities, correctional facilities, drug treatment facilities,
and shelters for the homeless), and a deterioration of the public
health care infrastructure.
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Drug-resistant tuberculosis in the United States
Until recently, the national surveillance system for tuberculosis
has not included the reporting of drug susceptibility. Therefore,
information about trends in drug-resistant tuberculosis is limited.
Several regional surveys and some larger national surveys provide
some information, but methodological differences make comparing
the surveys difficult. The Centers for Disease Control and Prevention
(CDC) has conducted several surveys of primary drug resistance.
The first survey examined drug susceptibility results among tuberculosis
patients hospitalized between 1961 and 1968. Resistance to at least
one drug was found in 3.5% of the 9350 strains tested, and resistance
to two or more drugs was found in 1% of the strains tested (7,8).
In a second survey of city and state laboratories that was conducted
between 1975 and 1982, 6.9% of the cases involved resistance to
one or more drugs, and 2.3% of cases involved resistance to two
or more drugs (9-11). The third survey,
conducted between 1982 and 1986, found that 9% of strains isolated
in 31 health department laboratories were resistant to one or more
The difference in primary resistance rates in the three surveys
may be due to methodological differences; however, each survey showed
a rate of primary drug resistance that was relatively low and that
was stable or decreasing during the study period. Drug resistance
did not appear to be an increasing problem, and the surveys were
Prompted by outbreaks of multidrug-resistant tuberculosis, CDC
conducted an additional survey of drug resistance among tuberculosis
cases reported from January through March 1991 (13).
CDC then conducted a second survey of cases reported in the first
quarter of 1992, and compared the findings from that survey with
the findings from the 1991 survey (CDC, unpublished data, 1995).
The proportion of culture-positive patients with drug susceptibility
test results increased from 81.8% in 1991 to 84.1% in 1992. In 1991
resistance to at least one drug was found in 13.4% of new cases,
26.6% of recurrent cases, and 14.2% of cases overall; in comparison,
in 1992 resistance to at least one drug was found in 12.8% of new
cases, 19.4% of recurrent cases, and 13.1% of all cases. Resistance
to both isoniazid and rifampin was reported in 3.2% of new cases,
6.9% of recurrent cases, and 3.5% of all cases in 1991, and was
reported in 3.4% of new cases, 3.7% of recurrent cases, and 3.3%
of all cases in 1992.
The findings of these two surveys may not be comparable to the
findings of the previous surveys because of significant methodological
differences. In the previous surveys, susceptibility testing was
performed at a single laboratory on isolates from only a sample
of areas. In contrast, in the 1991 and 1992 surveys, susceptibility
tests were performed at local laboratories, and researchers attempted
to collect results from all areas for all of the cases reported
during the study period. Furthermore, in the previous surveys, attempts
were made to determine whether "new" cases had a history
of previous treatment and if so, to exclude them from the study,
whereas in the 1991 and 1992 surveys, classification of cases as
"new" or "recurrent" was not verified, and a
history of prior treatment was not sought. Although the full effect
of these methodological differences cannot be determined, the most
recent CDC survey suggests that drug resistance has increased in
the United States after years of relative stability.
Some regional data suggest that the increases in drug-resistant
tuberculosis may be concentrated in large urban areas. In the 1991
CDC survey, 67% of the cases of drug resistance were reported from
only five areas: New York City, California, Texas, New Jersey, and
Florida. In both the 1991 and the 1992 survey, 61% of the cases
of multidrug-resistant tuberculosis were reported from New York
City alone. Frieden and colleagues conducted a survey in New York
City of drug susceptibility results on specimens from all patients
with a positive culture for M. tuberculosis during April
1991 (14). They found that of patients
with no previous treatment, 23% had organisms resistant to at least
one drug and 7% had organisms resistant to both isoniazid and rifampin.
Beginning in 1993, results of drug susceptibility tests were reported
to CDC from all 50 state health departments and from New York City,
the District of Columbia, and Puerto Rico through SURVS-TB, CDCs
national TB surveillance system. In an analysis of areas reporting
susceptibility results for at least 75% of culture-positive cases,
New York City accounted for 80% of the cases of multidrug-resistant
tuberculosis (CDC, unpublished data, 1995).
Factors associated with drug resistance
One important risk factor for drug resistance is previous treatment
with antituberculosis medications (Table
1). Studies have found that rates of drug-resistance increase
as the duration of previous treatment increases (14,15).
In most instances, drug resistance develops because of inadequate
or erratic therapy, although it has been shown that persons previously
treated for drug-susceptible tuberculosis can be reinfected with
drug-resistant strains (16-18).
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Another risk factor for drug-resistant tuberculosis is contact
with a person who has infectious, drug-resistant tuberculosis. Recent
nosocomial outbreaks demonstrate a strong correlation between previous
exposure to a patient who has infectious, multidrug-resistant tuberculosis
and the subsequent development in the contact of multidrug-resistant
tuberculosis (19-23). Drug resistance occurs
more frequently in persons from areas of the world with a high prevalence
of drug-resistant tuberculosis, such as Southeast Asia, Latin America,
Haiti and the Phillippines. Several studies have found high rates
of primary drug resistance in these persons, indicating transmission
of drug resistant tuberculosis in the country of origin (24-27).
However, because an accurate history of treatment may be difficult
to obtain, some previously treated patients may be misclassified
as having primary resistance. In the CDC survey conducted from 1982
to 1986, the rates of both primary and acquired drug resistance
were two times higher among foreign-born persons than among persons
born in the United States (12).
Outbreaks of Drug-Resistant Tuberculosis
Drug-resistant tuberculosis was described soon after antituberculosis
drugs were introduced, but the first documented outbreak of drug-resistant
tuberculosis was not reported until 1970. Between 1970 and 1990,
only a few outbreaks of isoniazid-resistant tuberculosis and five
outbreaks of multidrug-resistant tuberculosis were reported. In
general, these outbreaks involved small numbers of cases among close
contacts who had prolonged or repeated exposure to source patients
From 1990 through August 1992, in collaboration with state and
local health departments, CDC investigated outbreaks of multidrug-resistant
tuberculosis in seven hospitals in Florida, New York, and New Jersey
and in the New York State correctional system (Tables
2 and 3) (19-23,
34-40). The recent outbreaks differ considerably
from previous outbreaks of drug-resistant tuberculosis in several
ways. First, the recent outbreaks involved large numbers of patients;
nearly 300 cases have been identified. In addition, in the recent
outbreaks tuberculosis was transmitted not only from patient to
patient but also from patient to health care worker. The epidemiologic
evidence of nosocomial transmission was confirmed by DNA fingerprinting
data: strains from epidemiologically linked cases were found to
have identical patterns by restriction fragment length polymorphism
(RFLP) analysis. RFLP analysis also suggested that several of the
outbreaks in New York State were connected.
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Finally, the recent outbreaks involved a large percentage of highly
susceptible patients who became infected with highly drug-resistant
organisms that are more difficult to treat. More than 80% of the
cases occurred in persons infected with HIV, and all but six of
the patients had organisms resistant to both isoniazid and rifampin.
Mortality in these outbreaks was very high. In seven of the eight
outbreaks, more than 70% of the patients died. The median interval
between diagnosis and death ranged from 4 to 16 weeks.
Factors associated with the outbreaks of multidrug-resistant
Most of the outbreaks were centered in wards or outpatient clinics
where HIV-infected persons received care. There is no evidence that
persons with HIV infection are more likely to be infected with tuberculosis
if exposed, but it is clear that, once infected with tuberculosis,
persons who are infected with HIV have a much higher risk for the
development of active disease than persons who are not infected
with HIV. In addition, infection may progress to active disease
rapidly. The transmission of tuberculosis to HIV-infected persons
in these outbreaks was followed by the rapid development of new
cases of active disease, which were sources of further transmission.
Prolonged infectiousness also promoted transmission. The diagnosis
of tuberculosis in HIV-infected persons was sometimes delayed because
of the unusual radiographic presentations of tuberculosis, coinfection
with other pulmonary pathogens to which patients' symptoms were
attributed, and the overgrowth of M. tuberculosis in the
laboratory by other mycobacteria. Delays in diagnosis lead to delays
in the initiation of isolation and treatment. In addition, drug
resistance was not recognized promptly because of lengthy laboratory
delays, which postponed the initiation of effective treatment and
resulted in prolonged infectiousness.
Inadequate infection control practices also facilitated transmission.
Isolation rooms were found to be at positive pressure relative to
other parts of the facility. Patients who had been assigned to isolation
rooms were found in hallways, patient lounges, or other common areas.
Furthermore, isolation precautions were discontinued prematurely,
after an arbitrary number of days, rather than when there was clinical
or laboratory evidence of decreased infectiousness.
Finally, some patients who were given appropriate therapy in the
hospital were lost to follow-up after discharge. A lack of consistent
follow-up after discharge promotes lapses in therapy and heightens
the potential for transmission both in the hospital and in the community.
This problem was not specifically addressed in the outbreak investigations,
but it was described in an unrelated report by Brudney and Dobkin.
They studied 224 tuberculosis patients admitted to Harlem Hospital
in 1988. Of 178 patients discharged on tuberculosis treatment, 89%
were lost to follow-up and did not complete therapy. Forty-eight
patients were readmitted to the hospital with infectious tuberculosis
within 1 year (41).
The Advisory Council for the Elimination of Tuberculosis has
issued recommendations aimed at preventing drug-resistant tuberculosis
(42). Drug susceptibility tests should
be performed on all initial isolates of M. tuberculosis.
Additional isolates should be tested for patients whose cultures
remain positive after 3 months of therapy or who have signs of failure
or relapse. Susceptibility testing not only guides clinical therapeutic
decisions, but also allows tuberculosis control programs to monitor
drug resistance trends and evaluate tuberculosis control efforts.
Second, initial regimens for treating tuberculosis should include
four drugs: isoniazid, rifampin, pyrazinamide, and either ethambutol
or streptomycin. When drug susceptibility results become available,
the regimen can be adjusted accordingly. More drugs may be required
for initial regimens in institutions where outbreaks of multidrug-resistant
tuberculosis are occurring. In areas where resistance to isoniazid
or rifampin is less than 4%, an initial regimen of three drugs may
be adequate. The continued surveillance of drug resistance is necessary
to detect changes in local drug resistance patterns and to evaluate
the appropriateness of initial regimens in given areas.
Third, therapy for tuberculosis should be directly observed by
a health care provider. Nonadherence to therapy is a major cause
of treatment failure, and it may contribute to the emergence of
drug resistance. Directly observed therapy (DOT) is an effective
way to ensure adherence, but the method must be tailored to each
patient's needs and preferences.
Tuberculosis that is resistant to isoniazid alone can be treated
successfully by using rifampin and ethambutol for a minimum of 12
months, preferably supplemented by pyrazinamide for the first 2
months. In addition, a four-drug regimen has been shown to be highly
effective for isoniazid-resistant organisms. Rifampin resistance,
however, significantly reduces cure rates and increases the complexity
and the required length of treatment (43).
The treatment of multidrug-resistant tuberculosis should be based
on the in vitro susceptibility test results and the patient's
treatment history (5,44,45).
The regimen should include at least three drugs preferably
drugs that the patient has not received before to which the
patient's organism is susceptible. The regimen should include an
injectable medication whenever possible. If the regimen must be
changed for any reason, two medications should be added simultaneously
to avoid selecting for drug-resistant mutants.
Medications used to treat multidrug-resistant tuberculosis are
less effective, more costly, and more likely to cause adverse reactions
than the five first-line drugs (44-48).
Treatment is further complicated because of the length of therapy
needed to prevent relapse: generally, therapy for multidrug-resistant
tuberculosis should continue an additional 18 to 24 months after
culture results convert to negative.
Because of the high failure and relapse rates associated with multidrug-resistant
tuberculosis, surgical resection has been used by some clinicians
to supplement medical therapy. The surgical resection of a major
pulmonary focus is best performed once aggressive medical therapy
has achieved a clinical response. The administration of antituberculosis
medications should continue for 18 to 24 months after culture results
convert to negative. Iseman and associates reported that in a series
of 99 patients being treated for multidrug-resistant tuberculosis,
the combination of surgical resection and medical therapy produced
lower rates of failure and relapse compared with that of historical
Preventive Therapy for Persons Exposed to Multidrug-Resistant
When taken appropriately, isoniazid preventive therapy is very
effective in preventing the development of active tuberculosis in
persons infected with susceptible strains of M. tuberculosis,
even in persons coinfected with HIV. Rifampin is recommended for
persons infected with isoniazid-resistant strains (43,50).
In the outbreaks of multidrug-resistant tuberculosis, numerous
tuberculin skin test conversions were documented among persons exposed
to multidrug-resistant tuberculosis. Preventive therapy for persons
exposed to multidrug-resistant tuberculosis has not been studied,
but CDC has published guidelines for the management of such contacts
(51). Decisions regarding preventive therapy
should be based on the likelihood that the contact has been newly
infected, that the infecting organisms are multidrug-resistant,
and that active tuberculosis will develop. If the likelihood of
these factors is low, standard preventive therapy is recommended.
Alternative regimens should be considered for persons who are likely
to be newly infected with a multidrug-resistant strain and who are
at high risk for the development of active disease if infected.
CDC recommends that alternative regimens include at least two drugs
to which the infecting organism is known to be susceptible. Potential
alternative regimens include pyrazinamide and ethambutol or pyrazinamide
and a quinolone (e.g., ciprofloxacin) for 6 to 12 months.
Controlling the tuberculosis epidemic and preventing drug-resistant
tuberculosis necessitate that health care providers diagnose tuberculosis
early and initiate effective therapy promptly and that tuberculosis
patients successfully complete therapy. Specifically, directly observed
therapy should be used more widely, initial treatment regimens should
be used that prevent the development of drug-resistant tuberculosis,
and treatment activities should be coordinated between public health
departments and other facilities that provide care for patients
with tuberculosis. Surveillance of drug resistance must be done
to determine the appropriate initial regimen for tuberculosis in
given areas, define risk factors for drug resistance, and detect
transmission of drug-resistant tuberculosis.
Furthermore, appropriate infection control practices must be used
to prevent the transmission of tuberculosis in health care settings
(52). Different infection control measures
interrupt the transmission of tuberculosis at different points in
the transmission process. The most effective infection control measures
curb transmission at the source by preventing the generation of
infectious droplet nuclei. Examples of administrative control methods
include the early diagnosis of disease and prompt initiation of
effective therapy for persons with active tuberculosis, preventive
therapy for persons with tuberculosis infection, and instruction
of patients to cover their noses and mouths with a tissue when coughing.
Booths and hoods used for aerosolized pentamidine or sputum induction
are other examples of source control measures.
Potentially infectious patients should be placed in tuberculosis
isolation in a private room that has negative pressure relative
to the rest of the facility. The air from the room should be exhausted
directly to the outside or through a high-efficiency particulate
air (HEPA) filter, if recirculation of air into the general ventilation
system from the room is unavoidable. Isolation should be continued
until the patient is no longer infectious. Patients known or suspected
to have active tuberculosis should be considered infectious if they
are coughing, if they are undergoing cough-inducing procedures,
if their sputum smears contain acid-fast bacilli, if they are not
receiving antituberculosis chemotherapy, if they recently started
receiving chemotherapy, or if they are not responding to therapy.
Most patients with drug-susceptible disease become noninfectious
after 2 to 3 weeks of therapy, but the period of infectiousness
varies from patient to patient. Patients with drug-susceptible disease
who are receiving effective therapy and who show signs of response
to therapy (i.e., a reduction in cough, the resolution of fever
and a decreasing number of bacilli on sputum smears) are probably
no longer infectious. However, patients with drug-resistant disease
may take longer to respond to therapy, especially if drug resistance
is not suspected and they are not receiving effective therapy. Therefore,
patients should be considered infectious until their sputum smears
are free of bacilli on 3 consecutive days.
Ventilation and other engineering controls can be used to eliminate
infectious droplet nuclei once they are released into the air, but
these infection control measures are less efficient and less effective
than administrative control methods. Ventilation reduces airborne
contaminants by introducing uncontaminated air into the room, thereby
diluting the concentration of contaminants. The contaminants are
removed by exhausting the air from the room directly to the outside.
Potential supplemental measures include HEPA filters and germicidal
ultraviolet irradiation. These supplemental measures require proper
installation and regular maintanence by qualified personnel, and
their use in preventing tuberculosis transmission has not been well
studied. Furthermore, exposure to ultraviolet irradiation may pose
substantial health risks. Short-term exposure to germicidal ultraviolet
irradiation is known to cause keratoconjunctivitis and erythema,
and long-term exposure has been associated with an increased risk
of basal cell carcinoma.
Of all infection control methods, the use of personal protective
equipment is the least efficient and least effective. These devices
protect only the wearer, and they function only when they fit properly
and are worn correctly. Administrative controls and engineering
controls are necessary to protect all persons in the facility from
airborne contaminants. Personal protective devices should be worn
by health care workers in areas where the air is likely to be contaminated
with a higher concentration of infectious droplet nuclei such as
isolation rooms or rooms used for cough-inducing procedures.
A tuberculosis screening and prevention program for health care
workers is an essential component of infection control programs
in health care facilities. All persons working in health care facilities
should be skin tested upon employment. Persons who have negative
skin test results should be retested periodically. Screening will
detect tuberculosis infection in persons for whom preventive therapy
may be appropriate. In addition, skin test results must be analyzed
to evaluate the effectiveness of an infection control program by
determining whether tuberculosis is being transmitted in the facility.
Most cases of drug-resistant tuberculosis in the United States
can be prevented by using drug-susceptibility surveillance to monitor
trends, directly observed therapy to ensure adherence to and completion
of therapy, and initial regimens that include four drugs. Most of
the transmission of drug-resistant tuberculosis in health care settings
could be prevented by fully implementing the current CDC guidelines.
Additional research is needed to identify more rapid diagnostic
techniques, develop new drugs that are less toxic and require shorter
courses of treatment, and evaluate the role of supplemental infection
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