MAC: New Drug, Sparfloxacin, Enters Trials

A new member of the quinolone family of antibiotics is about to be tested against Mycobacterium avium complex (MAC, also called MAI) at twelve clinical trial sites around the U. S. The new possibility, called sparfloxacin, has been found to be more active against MAC than the older quinolones, including ciprofloxacin, in test-tube studies. Sparfloxacin was developed by Dainippon Pharmaceutical Company in Japan, where it has been tested extensively to treat gynecologic, skin, respiratory, and urinary tract infections. We spoke to a principal investigator of the MAC study, Lowell Young, M. D., of the Kuzell Institute in San Francisco, which will coordinate the laboratory results of all the various trial sites.

Dr. Young told us that this study is designed to determine the safety of the drug, although he is eager to watch for suggestions of effectiveness. The major side effects connected to sparfloxacin are skin sensitivity to sunlight or ultraviolet light, which was reported in French and Japanese patients on the drug, and digestive system problems in some Japanese patients.

As of press time, only five of the study's sites were ready to enroll participants:

* Denver, Colorado -- 303/893-7051

* Irvine, California -- 714/753-0670

* Orange, California -- 714/856-5454

* Portland, Oregon -- 503/494-7735

* San Francisco -- 415/561-1734.

We hope to publish the locations of the other sites for the sparfloxacin trial when they are ready to start; persons who miss this information and are interested in knowing the entry criteria and location of the other sites may call the U. S. commercial developer, Parke-Davis, in Ann Arbor, MI, at 800/521-3084, extension 7297.

MAC has been considered an unlikely infection to respond well to monotherapy (treatment with a single agent), and a number of antibiotics have been tried against MAC in various combinations and with various responses. In this trial participants will be given four weeks of sparfloxacin alone, and then four weeks in combination with ethambutol. The protocol for the study mentions that in test-tube studies this combination was synergistically active against nine of ten different strains of MAC, and the addition of rifampin to the ethambutol and sparfloxacin provided activity against all ten strains.

The last significant development in MAC research involved two promising new macrolide antibiotics -- clarithromycin and azithromycin (see AIDS TREATMENT NEWS #113, October 19, 1990). We asked about the potential value of combining sparfloxacin with one of these, and were told that in mouse studies, a combination of azithromycin and sparfloxacin obtained positive preliminary results -- but not as convincing, in the doses tested, as a combination of azithromycin, clofazimine, and amikacin. These last two drugs are already widely used to treat MAC in humans. Amikacin, however, is not recommended for extended maintenance therapy, which of course is necessary with AIDS-related MAC. So better combinations are still needed. When safe doses of sparfloxacin are established, the next logical step would be human studies combining the drug with one of the macrolides or other MAC drugs.

Meanwhile, azithromycin is just now successfully completing its own safety trials as a single agent against MAC, and the manufacturer, Pfizer, is scheduled to begin efficacy studies soon. Outside of clinical trials, Pfizer has made the drug available to treat toxoplasmosis through a compassionate use program. Interested physicians may call 203/441-5701. Similarly, for treating MAC, clarithromycin is available now from Abbott Laboratories through an open trial program (see AIDS TREATMENT NEWS #129). Interested physicians or patients may call 800/688- 9118.

Clarithromycin is also available through buyers' clubs in New York (212/532-0280) and Los Angeles (213/748-1295). We have not heard of buyers' club access for sparfloxacin or azithromycin.