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A Multi-Center Cross-Sectional Observational Study Of Antibiotic Resistance And The Genotypes Of Propionibacterium Acnes Isolated From Chinese Patients With Acne Vulgaris

Posted on:2017-08-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y K FanFull Text:PDF
GTID:1314330515459737Subject:Dermatology and venereology
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Background Acne vulgaris is a common chronic inflammatory disease involving the pilosebaceous units (PSUs), which mainly implicates teenagers and young adults.Numerous epidemiologic surveys performed in several provinces of China revealed an incidence rate of 36.4% to 54.9% among population aged 10 to 22 years, and more than 85% of the surveyed individuals reported developing acne lesions at least once during their lifetime. Propionibacterium acnes (P. acnes) are facultative anaerobic Gram-positive bacteria which reside in the PSUs and have long been deemed of contributing to the pathogenesis of acne vulgaris, such as hyperkeratinization, seborrhea and inflammation activation, although buzzing controversies still remains. Considering their marked therapeutic effects and also recommendation by several prestigious international guidelines,many kinds of antibiotics are widely applied in management of acne vulgaris for quite a long period, including China, which raises the issue of antibiotic resistance on a global scale.Many countries or regions, especially Europe, have conducted serial studies or prolonged surveillance of antibiotic resistance regarding P. acnes. However, due to improper antibiotics application and supervision, antibiotic resistance has become an emerging threat in Chinese public medical and health service. As with our profession,however, no comprehensive and persuasive domestic observational study concerning antibiotic resistance of P. acnes has been reported to date, so the efficacy of antimicrobial therapy in acne is unclear without an objective monitor in our country. This multi-centered study is aiming at obtaining a comprehensive and compelling data of antibiotic resistance conditions of acne patients in China, investigating potential relations between antibiotic resistance and the severity of disease and medication history, and hoping this knowledge could be informative and applicable in clinical practice. Moreover, there are several underlying mechanisms that might results in macrolides and tetracyclines resistance of P.acnes has been discovered. In our study a preliminary discussion on the mechanisms of antibiotic resistance has been conducted in order to verify the former theory.Objectives This cross-sectional, multi-center observational study is aimed at understanding the status of antibiotic resistance in P. acnes, by investigating the measures of acne management in several provinces in central China and analyzing the genotypes of antibiotic resistant strains of P. acnes.Methods Altogether 312 strains of P. acnes were collected from patients in 5 medical centers across China (Southwest Hospital Affilliated to the Third Military Medical University; Xijing Hospital Affilliated to the Fourth Military Medical University; The Second People's Hospital of Chengdu; The First Hospital of Wuhan; The First Hospital Affiliated to the Kunming Medical University) after reviewing the corresponding medical history in detail. The samples underwent antibiotic susceptibility assays by agar dilution method with a total of 11 classes of antibiotics being tested. The antibiotic-resistant strains were screened and further analyzed by investigation of the genotypes regarding 23 S rRNA,16S rRNA and erm(X). The statistic data are processed by Microsoft Excel and SPSS 19.0.The breakpoint of statistical significance is 0.05 (P=0.05).Results Altogether 364 individuals with acne vulgaris have accepted sampling and 312 strains of P. acnes,, one from each patient have been yielded by culture. The yielding rate is 85.7%. The gender ratio is 1: 1.65 (male vs female) and the average age of the whole cohort is 22.3 years, most of which suffered from mild to modest facial lesions. Around 70.5% of patients had received therapy before, and 61.4% of them had used antibiotics as part of their regimens. Most of the patients had used more than 2 classes of antibiotics as combined therapy. The predominant resistance occurred in macrolides and lincomycin with resistance rate of 47.8% in average, and congruent cross-resistant is observed between erythromycin, azithromycin and lincomycin (ML). The resistance to tetracyclines(including tetracycline, doxycycline and minocycline), chloramphenicol and moxifloxacin was scarce. Only 2 tetracycline-resistance cases have been identified while no minocycline-resistance strain detected. Also P. acnes are intrinsically resistant to metronidazole and sulfamethoxazole. The emergence of minimum inhibitory concentration(MICs) elevation (including resistant cases) for tetracyclines is associated with its application (P<0.005), but similar relation have not been discovered concerning ML. The genotypes of the reported macrolide-lincosamide-streptogramin B (MLSB) resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist.Tn5432 sequence is presented in more than 75% of tested strains, most of which are ML resistant.Conclusions P. acnes are universally residing in the skin lesions of acne patients implicating close association between the microbes and pathogenesis if acne vulgaris.Antibiotics are the most frequently used medication in management of acne in our country and combined therapies are much common. The emergence of tetracycline resistance correlates with its application history. The tetracyclines, chloramphenicol and quinolones have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China. P. acnes are intrinsically resistant to metronidazole and sulfamethoxazole; while fusidic acid is able to inhibit growth of P. acnes effectively, their MICs in this case is increased significantly compared to staphylococcus. There were no significant connection between carrying antibiotic resistant strains and severity of skin lesions. New underlying resistance determinants of ML and tetracyclines may exist, which require further elucidation. The results of this study has filled the gap of correlative data in China, and hoping it will serves as an instructive reference in clinical practice.
Keywords/Search Tags:acne vulgaris, Propionibacterium acnes, antibiotic resistance, genotype, China
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