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Excerpt
It is difficult to do compliance studies in any informed consent setting. The exclusion criteria almost always include the patients who are most likely to be noncompliant. Thus, there is almost certain bias toward compliance. This may well be one likely explanation for the failure to show therapeutic benefits of single-dose azithromycin compared with week-long regimens of doxycycline for treatment of chlamydial infections.2
However, the Bachmann study points out another potential explanation for the failure to show differences in therapeutic responses. In this study, 67% of the patients receiving a doxycycline course for genital chlamydial infection skipped at least one whole day of treatment. It has been axiomatic that to treat chlamydial infection, one has to use relatively long courses of treatment and maintain relatively high tissue levels of antibiotics. These studies suggest the possibility that the current recommendations are overkill. In other words, it must require less antibiotic to cure a chlamydial infection if a 65% compliance problem only results in a 5% failure rate. In part, it is probably because the CDC treatment guidelines often reflect caution. There is some assumption of less than optimal compliance in the treatment guidelines, as they typically call for more treatment (either dose or duration) than has been shown to be effective in treatment trials. With chlamydia, for example, many treatment trials found 1 gm of tetracycline (4 × 250 mg) or 100 mg of doxycycline once a day for 7 days to be effective treatment, but the guidelines called for 2 gm daily of tetracycline or 200 mg of doxycycline daily.
The Bachmann results confirmed a previous compliance study done with doxycycline, performed by some of the same researchers, that found only one fourth of patients were completely compliant with the regimen and essentially the same proportion was completely noncompliant.3 (Noncompliant is defined as taking >48 hours after leaving the clinic to start medication or having at least 1 day without doxycycline in any 5 consecutive day period.)
The bottom line, of course, is that we really don't know the minimally effective treatment for chlamydial infections. The first study did not look at tests of cure. However, the basic question of how much treatment is enough has not really been answered. Certainly, none of the earlier studies were done with tests of cure that have the sensitivity and ease of performance that today's nucleic acid amplification tests have. There is a suggestion, however, that less than the whole-recommended regimen is certainly effective in treating the great majority of infections.
The pharmacology of certain drugs may play a role here. For example, the high efficacy of azithromycin is due to its high and persistent intracellular antibiotic levels. Tetracyclines have good cell penetration, but are not concentrated and do not persist at such high levels. However, minocycline was presumed to have a higher lipid solubility profile and better cell penetration. Also, there is anecdotal evidence in the literature (that is largely ignored) that indicates that single-dose minocycline was highly effective at treating chlamydial genital infection.4 This was never confirmed by another group.
