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U.S. Department of Health and Human Services

  
Education Materials > Publications > Improving Patients Adherence to TB Treatment > Appendix

Improving Patient Adherence to Tuberculosis Treatment (1994)

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Appendix

Section Topics

Testing for the Presence of TB Drugs or Their Metabolites in Urine

Several simple, reliable, and relatively inexpensive tests for demonstrating the presence in urine of TB drugs or their metabolites have been developed. Methods for performing a variety of tests, by Eidus and Ling, were published in a World Health Organization technical bulletin in 1969. (1). More recently, others have published the methods and results of testing urine for the presence of isoniazid (INH) and its metabolites, pyrazinamide (PZA) and its metabolites, rifampin and its metabolites, and ethambutol (EMB) (2-6).

A procedure for detecting the INH metabolite isonicotinic acid in urine by using a reagent-impregnated paper test strip was described by Kilburn et al (5). This dipstick test measures the presence of the most widely used TB medication and can be conveniently incorporated into TB patient care (see instructions at end of the appendix). The Bacto INH test strips, for example, are available from Difco Laboratories, in Detroit, Michigan. The Potts-Cozart method (6), an alternative to the test strip method, is based upon a similar chemical reaction, may be less expensive, and was used by the Arkansas Department of Health.

Note: Caution is needed in the interpretation of results of urine tests for drug metabolites. For example, the reliability of INH test strips in clinical situations depends upon 1) the sensitivity and specificity of the strips in detecting the presence of isonicotinic acid in urine, 2) the rate at which individual patients metabolize INH, and 3) the timing of the test in relation to the time when pills are ingested.

The INH test strips were shown to be 99% sensitive (very few false-negatives) and 100% specific (no false-positives) for one group of patients when urine was collected 20 to 24 hours after pills were ingested, and it is believed that for most patients the test is reliable when conducted at any time within 24 hours after pills are ingested. However, the normal rate of INH metabolism differs in various patient populations, and the average time required for clearance of INH from the urine can be less than 4 hours.

In addition to normal differences between patients, which are constant over time, temporary factors such as fluid intake, illness, or dehydration may affect INH clearance and lead to false test results.

How to Test Urine for INH and Its Metabolites by Using Bacto INH Test Strips

  1. Store the test strips in the refrigerator at 20 to 80 C until ready to use.
  2. Ask the patient to collect a urine specimen in a small container.
  3. Each paper test strip is enclosed in a small plastic tube. Take one test strip enclosed in its sealed plastic tube from the jar. Cut off one corner of the plastic tube at the arrow end of the strip.
  4. At the opposite end of the strip from the arrow, squeeze about 1/2 inch of the plastic tube between thumb and forefinger (to create a suction) and insert the cut end of the tube into the urine specimen, below the surface.
  5. Release pressure between thumb and forefinger, drawing urine into the plastic tube. Liquid should rise in the tube to cover the arrow on the paper strip.
  6. The tube may now be left to float in the urine container or may be transferred to a test tube.
  7. Keep the tube at room temperature and observe results in 15 to 30 minutes.
  8. Look for a blue, purple, or green color on the strip and in the liquid in the tube. These colors are a positive test result, indicating the presence of INH or its metabolites in the specimen. If the reaction is weak, only the paper strip may appear colored.

Note: Use Bacto INH control disk each time a urine test is conducted. (See instructions on the package of control disks for storage and use recommendations.)

References

  1. Eidus L, Ling GM. Tests for the detection of antituberculosis drugs or their metabolites in the urine. WHO Tech Bull 1969;76:1-9.
  2. Burkhardt KR, Nel EE. Monitoring regularity of drug intake in tuberculosis patients by means of simple urine tests. S Afr Med J 1980;57:981-5.
  3. Kirsten C, Armstrong C, Gatner EMS. A simple test for the identification of ethambutol in urine. S Afr Med J 1980;58:992.
  4. Ellard GA, Grenfield C. A sensitive urine-test method for monitoring the ingestion of isoniazid. J Clin Pathol 1977;30:84-7.
  5. Kilburn JO, Beam RE, David HL, Sanches E, Corpe RF, Dunn W. Reagent-impregnated paper strip for detection of metabolic products of isoniazid in urine. Am Rev Respir Dis 1972;106:923-4.
  6. Henderson WT. The development and use of the Potts-Cozart tube test for the detection of isoniazid (INH) metabolites in urine. J Ark Med Soc 1986; 82(10):445-6.

 


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