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Study questions relevance of antibiotic resistance

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Interesting study that indicates that antibiotics help acne more by reducing inflamation rather than by killing the p acnes bacteria.

San Francisco  The prevalence of Propionibacterium acnes resistance in antibiotic-treated acne patients is high, but appears to be of no clinical relevance, likely because the mechanism of action of antibiotics in clearing acne relates to anti-inflammatory activity. This is according to Anthony C. Chu, M.D., speaking at the 64th Annual Meeting of the American Academy of Dermatology, here.

Dr. Chu and colleagues from Hammersmith Hospital, London, presented the results from a two-part study. This study was designed to investigate the prevalence and therapeutic relevance of P. acnes resistance in antibiotic-treated acne patients and the effect of antibiotics on cell-mediated immune responses.

Antibiotics vs. bacteria

The researchers performed sensitivity testing of P. acnes isolated from the facial skin of 135 acne patients who had been treated with a standard dose of one of five antibiotics (trimethoprim, tetracycline, minocycline, erythromycin or clindamycin) for at least four months. Those in vitro studies revealed bacterial resistance to antibiotic levels achieved in the skin was common, but the laboratory findings had no-to-minimal correlation with the patient's clinical responses.

In the second phase of the study, the effect of antibiotics on peripheral mononuclear blood cell (PBMC) proliferation stimulated by exposure to P. acnes sonicates was investigated, and the results showed the antibiotics had a marked inhibitory effect.

"Rising P. acnes antibiotic resistance has been described in a number of studies as a growing problem and has led to foretelling of doom and gloom regarding the future efficacy of antibiotics for the treatment of acne. Our findings suggest this trend will almost certainly not result in loss of antibiotic utility for this disease," says Dr. Chu, senior lecturer and consultant dermatologist, Hammersmith Hospital.

"However, antibiotics may lose their role in the management of acne in the future because their widespread use is promoting Staphylococcus epidermidis resistance that will be transferred to Staphylococcus aureus and translate into a clinically significant problem with multiresistant strains of that pathogen."

Resistance of P. acnes in the acne patients was studied by plating facial swabs on two sets of selective media containing one of the five antibiotics at concentrations representing either the standard used for investigating antibiotic resistance or the average level achieved in the skin with standard oral or topical therapy. The latter concentration was derived based on published reports and considered as the concentration of clinical relevance. Resistance was defined as growth of two or more colonies on the selective media with no growth on a control plate using non-selective media that is standard for P. acnes cultures.

Resistance high, yet outcomes good

Resistance of P. acnes to both erythromycin and trimethoprim was generally high whether considering bacteria isolated from all patients or just the ones on those antibiotics and in both the cultures containing the standard antibiotic concentration and skin antibiotic concentration. For tetracycline and clindamycin, resistance rates were relatively high in the standard antibiotic media and lower in the cultures prepared with antibiotic at the skin concentrations. For all patients, the resistance rates of both agents in the cultures containing the skin antibiotic concentrations were Â?14 percent.

"The standard levels of tetracycline and clindamycin used for resistance testing are much lower than the concentrations achieved in the skin, and that discrepancy explains the difference in resistance rates between these two test situations," Dr. Chu notes.

While resistance to minocycline was low in the overall population, it was 66 percent for P. acnes derived from minocycline-treated patients cultured in media containing antibiotic at the achieved skin concentration. That rate was much higher than anticipated based on published reports, Dr. Chu says

The effect of bacterial resistance on patient outcomes was evaluated by dividing patients according to whether they were colonized with resistant or nonresistant P. acnes and then determining the proportions of patients who achieved a good clinical response (50 percent or greater improvement in acne grading over a two-month period) within each group. Not only was there little to no correlation between drug resistance and clinical response, but the rates of good responses were higher in the resistant patients than in those with non-resistant P. acnes for four of the five antibiotics (75 percent to 100 percent vs. 65 percent to 85 percent). The differences, however, did not reach statistical significance.

Bacterial eradication irrelevant?

Testing of the effects of antibiotics on PBMC responses was performed recognizing that the pathogenesis of acne is thought to involve a T-cell mediated immune reaction to a P. acnes antigen. For that research, the bacteria were grown in media containing a fatty acid content mimicking the sebum of acne patients (ie., enriched in oleic acid) and then sonicated to produce antigen for stimulating PBMCs isolated from 30 acne patients and 15 unaffected controls.

The results showed there was no difference in the proliferative responses of the PBMCs from the acne patients compared with the controls. That finding was not surprising considering the potent antigenicity of P. acnes, Dr. Chu says.

However, when the studies were repeated in the presence of antibiotics at the concentrations achieved in the skin or serum, the majority of the antibiotics inhibited cellular proliferation, and again there was no difference between the acne patients and controls. "This effect on the PBMCs explains why the antibiotics were associated with a good clinical response despite the presence of bacterial resistance. In other words, therapeutic activity does not depend on bacterial eradication. In that sense, the efficacy of antibiotics in treating acne is analogous to the situation of rosacea where the inflammatory lesions respond to antibiotic treatment even though P. acnes is not involved in their pathogenesis," Dr. Chu says.

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