Trial Indicates Azithromycin Therapy May Be Beneficial for Subset of CFS Patients; Raises Questions for Continuing Research

In a group of 99 Chronic Fatigue Syndrome patients treated experimentally for six weeks with azithromycin, a subgroup of 58 patients reported a positive decrease in overall symptom severity. Azithromycin is an antibiotic, but is also believed to possess beneficial immunomodulation (immune system affecting) abilities.

Changes in patients’ symptoms were determined by comparisons of extensive pre- and post-trial self-assessments. Their global impressions of change were scored as: improvement, no change, and worsening of symptoms. Patients were then classified as “responders” and “nonresponders.” No patients experienced worsening.

The researchers, working in the CFS and Pain Research Center in Amsterdam, speculate that the overall improvement in symptoms for the responder subset may be owing to azithromycin’s ability to reduce the bacterial load in these individuals’ systems, and/or its ability to modulate the immune cells in their brains or peripheral immune systems. CFS is often associated with greater susceptibility to episodic and chronic infections, and with a chronically activated or “primed” immune system that may be associated with some symptoms.

More-specific findings of this study were that:
n The average improvement for the 58 “responders” was not great, but exceeded the maximum improvement they had experienced with previous fluctuations in their condition. Also, the proportion of responders in the study group (59 percent) exceeds the average 19.6 percent of CFS patients who have responded positively to placebo or “fake” doses in previously reported therapy trials.
n On an individual case basis, none of the responders improved enough to achieve pre-CFS symptom status (full recovery), though the maximum estimated individual improvement was 80 percent.
n The responders tended to be younger (average age 34.7, standard deviation plus or minus 11.5 years) than the nonresponders (average age 40.3, plus or minus 12.7 years).
n As noted in an item-by-item table, improvements noted in the responders were associated with measures of fatigue according to the Multidimensional Fatigue Inventory, and included general, physical, and mental fatigue; activity, and motivation. Their average pain score was also slightly improved. But average scores on measures of psychological symptoms such as depression anxiety, and distress were slightly less positive for the responders.

Another finding of the study was that, after the azithromycin treatment, the responders’ blood plasma levels of acetylcarnitine were lower on average than for the nonresponders. The researchers speculate that the reason for the lower acetylcarnitine levels in the responders’ blood has to do with cellular energy production. Acetylcarnitine is involved in the cells’ normal use of fatty acids to produce energy (oxidation). They cite studies offering preliminary evidence of a relationship between CFS patients’ fatigue and dysfunction of cellular energy production, indicating “a complex response involving acetylcarnitine.” Are the responders’ cells using more acetylcarnitine, for example?

Background. The researchers have been experimenting with various clinical therapies for CFS patients. The patients involved in the azithromycin trial had previously taken part in trials of counseling therapy and supplementation with L-carnitine (delivered to the cells as acetylcarnitine). But neither therapy had produced a “sufficient” effect. Participants were those who elected to try yet another therapy, and were not selected based on measures of symptoms or immune activity. Further, retrospective review concluded that the histories and physical examinations of the responders and nonresponders were not indicative for the differences in their response.

Dosage and side effects. The patients received 500 mg of azithromycin on three consecutive days of each week during the six-week trial. The only side effects were “minor bowel problems that resolved by dividing the daily dosage of azithromycin.”

The article describing this trial, “Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data,” by Ruud C.W. Vermeulen and Hans R. Scholte, was published August 15, 2006 by the Journal of Translational Medicine. The full text of the article with tables and footnotes citing associated studies is available for free review and download at http://www.translational-medicine.com/content/4/1/34

Note: The information provided here is not intended to diagnose, treat, cure, mitigate, or prevent any disease.