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Failure to Mention Fixed-Dose Drug Combinations in the ATS/CDC/IDSA Tuberculosis Control Statement/From the Authors

Posted on: Friday, 24 March 2006, 09:00 CST

By Moulding, Thomas; Nolan, Charles M; Taylor, Zachery; Blumberg, Henry M

To the Editor.

The recent American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America (ATS/CDC/ IDSA) statement on the control of tuberculosis (TB) emphasized directly observed therapy (DOT) and included the word DOT 31 times, but failed to mention fixed-dose combinations (FDCs) of anti-TB drugs (1). By contrast, an earlier ATS/ CDC/IDSA statement on treatment of TB recommended the use of FDCs when DOT is given daily or when DOT is not possible for three reasons: ease of administration; potential for reducing medication errors; and preventing the patient from taking a single drug (monotherapy) which, if taken, greatly increases the chance that drug resistance will develop (2). The importance of this treatment recommendation has been confirmed by the finding of very low rates of acquired drug resistance to Mycobacterium tuberculosis, less than 0.3%, among 4,000 HIV-negative patients taking self-supervised therapy (SST) in Los Angeles (3). FDCs of anti-TB drugs are not widely used in the United States. The ratio of money spent for FDCs containing rifampin to individual rifampin pills is approximately 10 to 1 (Mr. Joe Ware, Versapharm, Inc.).

Despite the emphasis on DOT by the ATS/CDC/IDSA, a significant proportion of patients are being treated with SST, since only 78% receive DOT alone or in combination with SST (1). Much of the SST is given in the non-health department private sector, which treats 22% of all patients for the entire duration of therapy plus 21.9% in the initial phase of therapy when the bacterial populations are large and the chance of developing drug resistance is high (4). Since use of DOT by private physicians is rare and not likely to change, use of FDCs in the private sector is particularly important to prevent acquired drug resistance. To correct this deficiency in the recent TB control statement, special directed efforts to promote the widespread use of FDCs need to be carefully considered and vigorously pursued.

Conflict of Interest Statement: T.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

THOMAS MOULDING

Harbor UCLA Medical Center

Torrance, California

References

1. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America. Controlling tuberculosis in the United States. Am J Respir Crit Care Med 2005;172:1169-1227.

2. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America. Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-662.

3. Moulding TS, Le HQ, Rickleen D, Davidson P. Preventing drug resistant tuberculosis with a fixed dose combination of isoniazid and rifampin. Int J Tuberc Lung Dis 2004;8:743-748.

4. Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 2004. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2005.

From the Authors:

We are pleased to respond to Dr. Moulding's letter, because it gives us the opportunity to emphasize an important point about the new American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America (ATS/ CDC/IDSA) statement (1). This statement, comprehensive as it is, does not stand alone in providing recommendations for diagnosis, treatment, prevention, and control of tuberculosis (TB) in the United States. Rather, the statement is one of a series that are issued periodically by the sponsoring organizations (1-4) to guide the spectrum of activities associated with the management and control of TB. This statement makes recommendations for organizing the process of TB control in the United States, including a description of the essential activities and the roles and responsibilities of the range of participants. It was not designed to reiterate recommendations on standards of diagnosis and treatment of TB and latent infection, which are covered in detail in the other current statements (2-A).

As noted by Dr. Moulding, the statement on treatment of TB (2) makes explicit recommendations on practical therapeutic approaches to individual patients managed with directly observed and self- supervised therapy. Directly observed therapy (DOT) needed to be discussed in some detail in our statement because, to quote from the treatment statement, DOT is "the central element in a comprehensive, patient-centered approach to case management" (2) and as such is an essential component of the public health infrastructure for TB control in the United States today.

It is important to emphasize that TB treatment benefits not only the patient with the disease but also the community, and that every medical practitioner who undertakes such treatment assumes the responsibility to not only prescribe an appropriate regimen but also to assure adherence until treatment is completed (2). Collaborative arrangements between practitioners and public health agencies are recommended by both recent ATS/CDC/IDSA statements (1, 2) to achieve this goal of therapy.

These practical issues of TB treatment, such as DOT, case management, and the use of fixed-dose drug combinations, derive their importance from their role in enhancing the likelihood that patients with TB complete the lengthy course of therapy that is necessary to cure the disease and avoid treatment failure, relapse, and the acquisition of drug resistance. New drug regimens that could reduce the length of treatment for TB would potentially lessen the administrative burden and intensity of resources needed for DOT and individualized case management. Work on new TB drugs has been intensifying (5), and there is reason for optimism that the length of standardized therapy for TB can be further reduced (6).

Conflict of Interest Statement: None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

CHARLES M. NOLAN

ZACHERY TAYLOR

HENRY M. BLUMBERG

Co-Chairs of the Ad Hoc Committee of the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America

References

1. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America. Controlling Tuberculosis in the United States. Am J Respir Crit Care Med 2005;172:1169-1227.

2. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America. Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-662.

3. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161:1376-1395.

4. American Thoracic Society/Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221- S247.

5. O'Brien RJ, Spigelman M. New drugs for tuberculosis: current status and future prospects. CUn Chest Med 2005;26:327-340.

6. Nuermberger EL, Yoshimatsu T, Tyagi S, Williams K, Rosenthal I, O'Brien RJ, Vernon AA, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med 2004; 170:1131-1134.

Copyright American Thoracic Society Mar 15, 2006

Source: American Journal of Respiratory and Critical Care Medicine

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