Characterisation of antibiotic-resistant Propionibacterium acnes from acne vulgaris and other diseases

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Laboratory Medicine

Sammanfattning: Propionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacterium that belongs to the normal microflora. The skin is the major habitat but it can also be found in other body regions. P. acnes plays an important role in the pathogenesis of acne vulgaris. The general perception is that P. acnes is a microorganism with low virulence, but during the last years, the prevalence of severe, life-threatening infections caused by P. acnes has increased, especially in immuno-compromised patients and in those with prosthetic devices. Long courses of antibiotics have been a mainstay of acne treatment. The consequence has been the development of antibiotic-resistant P. acnes. The aim of the present investigation was to perform a characterisation of P. acnes antibiotic-resistant clinical isolates collected from acne patients and various other diseases. The resistance pattern, genetic diversity and molecular resistance mechanisms have been studied. We have found that acne patients in Stockholm treated with antibiotics had a significantly higher risk of carrying resistant P. acnes strains, than acne patients who did not receive such a treatment. Furthermore, we have demonstrated that antimicrobial resistance has emerged among P. acnes strains isolated from different severe, lifethreatening infections in Europe. The prevalence of tetracycline resistant isolates was lower as compared to erythromycin and clindamycin resistant isolates. The bacterial resistance in P. acnes isolates obtained from various diseases mirrors the situation with antimicrobials presently in use in different countries. We have developed a new pulsed-field gel electrophoresis protocol as typing method for P. acnes strains. Pulsedfield gel electrophoresis is a powerful tool in epidemiology for the determination of clonal identity of bacteria. We have demonstrated that antibiotic-resistant P. acnes population is polyclonal and that skin isolates do not represent a separate pulsed-field type when compared with the bacterial population from other sites than the skin. We have shown that an acne patient may be colonized with different P. acnes strains with various resistance phenotypes, suggesting that certain bacterial clones are more prone to acquire resistance against a specific antibiotic. The resistant strains from acne and other diseases showed well-known mutations in the 23S rRNA and 16S rRNA, but also new mechanisms of resistance have evolved. It is conceivable that mobile genetic elements carrying resistance genes have developed and can be transferred to other pathogenic bacteria. There is a complex relationship between antibiotic resistance and outcome in acne vulgaris. It is still an open question how much of the antibiotic efficacy in acne is due to the anti-propionibacterial or anti-inflammatory effect. Treatment with oral tetracycline combined with a topical retinoid proved to be a good clinical alternative to oral isotretinoin, regardless of the presence of antibiotic-resistant P. acnes on the skin. The resistance seems to move from the acne patients to the community. We have shown that carriage of resistant P. acnes isolates occurs, not only in acne patients and their close contacts, but also in the general population. Close contacts within families were found to carry the same clonal type of antibiotic-resistant P. acnes as acne patients. The cost of resistance may be ameliorated by compensatory mutations causing the stabilization of the antibioticresistant bacterial population. Efforts should be made in preventing the development of resistance and the accumulation of antibiotic resistant P. acnes strains.

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