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

1. 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.

2. CDC. Primary resistance to antituberculosis drugs--United States. MMWR 1980, 29:345-6.

3. 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).

4. 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.

5. American Thoracic Society. Treatment of tuberculosis and other mycobacterial diseases. Am Rev Respir Dis 1983;127:790-6.

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