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Current Trends Primary Resistance to Antituberculosis Drugs --
United States
From March 20, 1975, through September 30, 1982, 20 city and
state
laboratories throughout the United States submitted 12,157
mycobacterial cultures to CDC for drug susceptibility testing as
part
of a survey of primary drug resistance (PDR) (1,2). PDR is defined
as
drug resistance among persons with tuberculosis (TB) who are not
known
to have had prior treatment with antituberculosis (anti-TB) drugs.
Mycobacterium tuberculosis organisms resistant to one or more
anti-TB
drugs were isolated from 6.9% of cases surveyed.
A marked decline occurred in the percentage of PDR over the
period
of the survey, and large differences were noted by race/ethnicity.
Figure 1 shows the generally declining trend and the markedly
higher
percentages of PDR among Asian and Hispanic cases (overall
percentages
were 14.8% - Asians; 11.8% - Hispanics; 6.1% - blacks; 4.9% -
whites;
and 4.1% - American Indians). Too few cultures were submitted from
American Indians for a meaningful display of the secular trend for
this group.
A highly significant (p = 0.005) inverse relationship was noted
between age and percentage of PDR. The PDR percentages ranged from
14.0% for ages 0-10 years to 3.6% for ages 91-99 years. PDR
percentages were highest for isoniazid (4.0%), streptomycin (3.8%),
and ethionamide (1.1%). Percentages for other drugs tested
(p-aminosalicylic acid (PAS)), rifampin, ethambutol, kanamycin,
capreomycin, and cycloserine) were less than 1%.
Table 1 shows the variation in percentages of PDR by geographic
area. Even after adjustment by logistic regression modeling for
differences between areas in race/ethnic and age distributions,
there
were substantial and statistically significant differences among
area-specific percentages, ranging from 3.9% for Washington State
to
11.3% for the border region of south Texas surrounding Harlingen.
Reported by Div of Tuberculosis Control, Center for Prevention
Svcs,
Div of Bacterial Diseases, Center for Infectious Diseases, CDC. Editorial Note
Editorial Note: The occurrence of PDR is an indicator of
transmission
of resistant organisms from TB patients who have received
inadequate
or inappropriate treatment. Thus, PDR percentages can serve as one
measure of the effectiveness of TB control programs.
The data from this survey show a relatively low level of PDR in
the United States. Furthermore, there has been a declining trend
for
PDR during the past 8 years. The reason for this decline is
uncertain; however, changing patterns of anti-TB therapy may be
partly
responsible. Using the drug combination of isoniazid and rifampin
has
been shown to decrease the likelihood that drug resistance will
emerge
during therapy (3). Increased use of chemotherapy with these two
drugs may offer at least a partial explanation for the decline.
Data from this study show higher percentages of PDR among Asian
and Hispanic populations and for areas where high concentrations of
these groups reside. The proportion of the Asian and Hispanic
population in this study who are foreign-born is not known; thus,
it
is impossible to ascertain whether the majority of drug-resistant
infections in these populations were acquired in the United States
or
in other countries. Furthermore, because of language barriers,
inaccurate histories about previous anti-TB treatment could
partially
explain the higher resistance percentages among Asians and
Hispanics.
However, PDR percentages are known to be higher among TB patients
from
the developing countries of Asia and Latin America (4); in these
countries, anti-TB drugs are available over the counter, and
self-medication is common. TB control programs in these countries
often do not have sufficient resources to give properly supervised
therapy, nor can they afford to use effective chemotherapy regimens
containing rifampin and isoniazid. These factors all increase the
risk of PDR.
In the United States, drug susceptibility testing of the
initial
M. tuberculosis isolate is indicated for (1) groups known to have a
higher prevalence of drug resistance, such as Asians and Hispanics,
(2) persons with a history of previous treatment with anti-TB
drugs,
(3) persons who fail to become culture negative by the fourth month
of
therapy, and (4) persons who have been exposed to drug-resistant TB
(5). Until results of drug susceptibility tests are available, a
patient should be treated with a regimen that includes at least two
drugs to which the infecting organisms are highly likely to be
susceptible. Subsequent modification of the regimen should be made
based upon test results and the patient's response to therapy.
References
Kopanoff DE, Kilburn JO, Glassroth JL, Snider DE Jr, Farer LS,
Good RC. A continuing survey of tuberculosis primary drug
resistance in the United States: March 1975 to November 1977.
A
United States Public Health Service cooperative study. Am Rev
Respir Dis 1978; 118:835-42.
CDC. Primary resistance to antituberculosis drugs--United
States. MMWR 1980, 29:345-6.
Snider DE Jr, Long MW, Cross FS, Farer LS. Six months
isoniazid-rifampin therapy for pulmonary tuberculosis: report
of
a United States Public Health Service cooperative trial. Am
Res
Respir Dis (in press).
Kleeberg HH, Boshoff MS. A world atlas of initial drug
resistance. Tuberculosis Research Institute of the South
African
Medical Research Council, Pretoria, South Africa, 1980.
American Thoracic Society. Treatment of tuberculosis and other
mycobacterial diseases. Am Rev Respir Dis 1983;127:790-6.
Disclaimer
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