Correspondence

Multiple-Antibiotic-Resistant Bacteria

N Engl J Med 1994; 331:678-679September 8, 1994

Article

To the Editor:

We share the concern expressed by Dr. Tomasz and his colleagues (April 28 issue) in the report on multiple-antibiotic-resistant pathogenic bacteria,1 particularly with regard to tuberculosis. However, we want to clarify an apparent misconception. The available data do not show that outbreaks of multidrug-resistant tuberculosis have occurred in 35 states, as noted in the report. Of the cases of culture-positive tuberculosis reported in the first quarter of 1991, cases of drug-resistant tuberculosis were identified in 36 states, and cases of multidrug-resistant tuberculosis, defined as tuberculosis resistant to isoniazid and rifampin (with or without resistance to other drugs), were identified in 13 states2. From 1990 to 1992, the Centers for Disease Control and Prevention, in collaboration with state and local health departments, investigated outbreaks of multidrug-resistant tuberculosis in only three states: New York, Florida, and New Jersey3.

The accompanying editorial by Dr. Murray (April 28 issue) raises the question, “Can antibiotic resistance be controlled”4? In the first quarter of 1991, 96.5 percent of patients with tuberculosis in the United States were infected with organisms susceptible to at least two of the three main drugs used for treatment (isoniazid, rifampin, and ethambutol),2 including 87.1 percent of patients in New York City and 98.1 percent of those in the rest of the nation. These data suggest that in almost all areas of the country, the recommended four-drug oral regimen of isoniazid, rifampin, pyrazinamide, and ethambutol should be adequate to prevent the emergence of drug resistance, if compliance with therapy can be ensured5.

However, patients with multidrug-resistant tuberculosis will not have a response to the recommended four-drug regimen. For these patients, other regimens are necessary6. It is essential that tests of drug susceptibility be performed on initial isolates from all patients to ensure that therapy is adequate. To be effective, programs for the control of tuberculosis must achieve early identification, isolation, and treatment of people with active infection. These three principles are also critical for controlling the transmission of tuberculosis in the community.

Alan B. Bloch, M.D., M.P.H.
Ida M. Onorato, M.D.
Kenneth G. Castro, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333

6 References

1. 1

   Tomasz A. Multiple-antibiotic-resistant pathogenic bacteria -- a report on the Rockefeller University workshop. N Engl J Med 1994;330:1247-1251
   Full Text | Web of Science | Medline

2. 2

   Bloch AB, Cauthen GM, Onorato IM, et al. Nationwide survey of drug-resistant tuberculosis in the United States. JAMA 1994;271:665-671
   CrossRef | Web of Science | Medline

3. 3

   Kent JH. The epidemiology of multidrug-resistant tuberculosis in the United States. Med Clin North Am 1993;77:1391-1409
   Web of Science | Medline

4. 4

   Murray BE. Can antibiotic resistance be controlled? N Engl J Med 1994;330:1229-1230
   Full Text | Web of Science | Medline

5. 5

   American Thoracic Society, Centers for Disease Control and Prevention. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994;149:1359-1374
   Web of Science | Medline

6. 6

   Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784-791
   Full Text | Web of Science | Medline

Author/Editor Response

Dr. Tomasz replies:

To the Editor: I appreciate the comments of Dr. Bloch and his colleagues. Indeed, their figures concerning reported cases of multidrug-resistant tuberculosis in the United States are the correct ones. However, it may be worthwhile to remember that multidrug resistance in tuberculosis is currently defined as resistance to two specific drugs: isoniazid and rifampin. Isolates with resistance to one of these drugs in combination with two, three, or even a larger number of other antibacterial agents are not called multidrug-resistant, according to current usage. Such strains with resistance, for instance, to isoniazid plus streptomycin plus ethambutol do exist.

Dr. Bloch and his colleagues also point out that tuberculosis isolates from most patients in the United States are susceptible to at least two of the three most frequently used drugs (isoniazid, rifampin, and ethambutol), and therefore the recommended four-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) should be adequate to prevent the emergence (i.e., acquisition) of drug resistance. Although this argument is probably correct, the clinical reality is unfortunately already past this point. A Mycobacterium tuberculosis strain (strain W) with resistance to seven antibiotics (isoniazid, rifampin, ethambutol, streptomycin, kanamycin, ethionamide, and rifabutin) has been reported in New York City, and clones of this strain may spread to other parts of the country.1

Alexander Tomasz, Ph.D.
Rockefeller University, New York, NY 10021-6399

1 References

1. 1

   Plikaytis BB, Marden JL, Crawford JT, Woodley CL, Butler WR, Shinnick TM. Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis. J Clin Microbiol 1994;32:1542-1546
   Web of Science | Medline