痤疮患者痤疮丙酸杆菌耐药性的研究进展

痤疮丙酸杆菌在痤疮发生中起重要作用。局部或系统使用抗生素治疗痤疮的炎症性损害，取得了很好的疗效。然而，近年来有关痤疮丙酸杆菌耐药导致痤疮治疗失败的报道逐年增多。概述了痤疮丙酸杆菌在痤疮发生中的作用、耐药现状及其发生机制，以及如何能够尽可能减少或避免耐药菌的产生，从而提高药物疗效。     

痤疮患者痤疮丙酸杆菌耐药性的研究进展

痤疮丙酸杆菌在痤疮发生中起重要作用。局部或系统使用抗生素治疗痤疮的炎症性损害 ,取得了很好的疗效。然而 ,近年来有关痤疮丙酸杆菌耐药导致痤疮治疗失败的报道逐年增多。概述了痤疮丙酸杆菌在痤疮发生中的作用、耐药现状及其发生机制 ,以及如何能够尽可能减少或避免耐药菌的产生 ,从而提高药物疗效。     

痤疮丙酸杆菌对大环内酯-林可酰胺类抗生素临床耐药表型分析

目的:了解痤疮丙酸杆菌对大环内酯-林可酰胺类抗生素交叉耐药和临床表型情况。方法:通过体外分离、培养、鉴定痤疮丙酸杆菌,使用琼脂稀释法进行体外药敏实验并使用韦恩图统计药敏交叉耐药数据结果。结果:156株痤疮丙酸杆菌对四种抗生素的药物敏感性试验中,17株对四种大环内酯-林可酰胺类抗生素全敏感,余139株对四种抗生素单一或多重耐药。其中二重耐药率为19. 4%(27/139),三重耐药率为5. 7%(8/139),四重耐药率高达28. 1%(39/139)。结论:东莞地区痤疮患者痤疮丙酸杆菌对大环内酯-林可酰胺类抗生素存在多重、交叉耐药,可能与大环内酯-林可酰胺类抗生素药物作用机理相似有关。     

寻常痤疮患者痤疮丙酸杆菌耐药性及其分子机制

目的:了解寻常痤疮患者中痤疮丙酸杆菌耐药情况,并探讨其可能的分子生物学机制。方法:选择18例寻常痤疮患者炎症性皮损,厌氧条件下分离、培养和鉴定获得12个痤疮丙酸杆菌临床株。采用纸片法对红霉素、克林霉素、甲硝唑和四环素4种常用抗生素进行体外药敏试验。根据药敏试验结果,选择对红霉素耐药菌株并提取细菌DNA,对23S rRNA基因扩增和测序,分析其核苷酸序列变化。结果:所有菌株均对四环素高度敏感而对克林霉素和甲硝唑均耐药,11个临床株对红霉素耐药,仅一株中度敏感。对12株23S rRNA序列经PCR测序后发现共7株发生第1392位A→G、第1393位A→G,第1518位A→G、第1533位T→C、第1569位A→G、第1814位G→A、第1839位G→A、第1946位T→C、第1974位A→G、第2034位T→C、第2058位A→T、第2273位A→G和第2513位T→C碱基变化,其余5株的核苷酸序列没有变化。结论:结合以前关于PA耐药基因的分子检测结果 ,除了已经报道的第2058位A→T变化外,本研究发现多个23S rRNA新突变位点以及同一菌株发生多位点突变,而部分菌株的核苷酸序列没有变...     

痤疮的抗生素治疗及耐药现状

痤疮丙酸杆菌在痤疮发生、发展过程中起着重要作用,外用或口服抗生素对痤疮炎性皮损有肯定疗效。然而随着抗生素的广泛使用,耐药问题日益严峻,研究表明超过50%的痤疮丙酸杆菌出现了耐药,尤其是对大环内酯类抗生素。本文对抗生素治疗痤疮的作用机理与使用现状、耐药机制与耐药现状进行综述。     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

痤疮患者痤疮丙酸杆菌对大环内酯类抗生素的敏感性分析

目的:了解广东省东莞地区痤疮患者痤疮丙酸杆菌对三种大环内酯类抗生素的敏感性情况。方法:采用质谱检测系统鉴定痤疮丙酸杆菌,琼脂稀释法测定痤疮丙酸杆菌对红霉素、阿奇霉素和克拉霉素的最小抑菌浓度(MIC)。结果:104例痤疮患者中分离出70株痤疮丙酸杆菌,对大环内酯类抗生素的耐药率从高到低依次为:阿奇霉素71.43%(50/70)、克拉霉素65.71%(46/70)、红霉素32.86%(23/70)。三种抗生素间存在交叉耐药。结论:东莞地区痤疮患者痤疮丙酸杆菌对大环内酯类抗生素有较高的耐药率并且存在交叉耐药,为该地区痤疮治疗的临床用药提供了借鉴。     

痤疮丙酸杆菌生物膜的构建

目的:构建痤疮丙酸杆菌的生物膜,明确其生长特性,以期更加深入了解痤疮丙酸杆菌的致病机制。方法:痤疮丙酸杆菌标准株及临床株分别接种厌氧肉汤,麦氏比浊法调整细菌浓度,接种96孔板,XTT法检测490nm吸光值,取平均值判定最佳成膜细菌浓度;菌液接种入装有盖玻片6孔板,厌氧培养,不同时间点进行扫描电镜(SEM)观察。结果:最佳成膜时间可以判定为接种后96h,最佳成膜浓度为1×108cfu/mL;两者形成生物膜的形态无明显差别。结论:本研究明确了痤疮丙酸杆菌的最佳成膜浓度,构建成其生物膜,为进一步研究痤疮丙酸杆菌奠定一定基础。     

The bacteriology of acne vulgaris and antimicrobial susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne lesions

We examined the species of bacteria aerobically and anaerobically isolated from 30 acne lesions and determined antimicrobial susceptibilities of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) using nine antimicrobial agents. Among the bacteria isolated, S. epidermidis was most dominant. Both P. acnes and S. epidermidis were isolated from half of the acne lesions. The MIC of seven antimicrobials (ampicillin, erythromycin, roxithromycin, clindamycin, tetracycline, minocycline, nadifloxacin) against P. acnes was under 3.13 micrograms/ml. There were very few resistant strains of P. acnes, but many of S. epidermidis. More than 30% of the S. epidermidis isolates were resistant to erythromycin, roxithromycin, and clindamycin. After long-term systemic antibiotic therapy, the resistant strains of S. epidermidis increased, but P. acnes resistance was still limited. When we use antimicrobial agents for the treatment of acne, it should be noticed that not only P. acnes but also S. epidermidis in the acne lesions may acquire resistance to antimicrobials.     

Antibiotic susceptibility of Propionibacterium acnes isolated from acne vulgaris in Korea

Propionibacterium acnes plays an important role in the development of acne, and inflammatory lesions are improved by antibiotics. Long-term use of antibiotics may result in development of resistant strains and treatment failure. The aim of the present study was to investigate the isolation rate of P. acnes and to evaluate its antibiotic susceptibility to widely used antibiotics in acne in Korea. Among 46 patients, 31 P. acnes strains were cultured. Isolated P. acnes was measured for minimum inhibitory concentration (MIC) of tetracycline, doxycycline, minocycline, erythromycin and clindamycin using an Epsilometer test. Age, disease duration and previous history of antibiotic therapy for acne were compared in relation to the MIC. The mean MIC of tetracycline, minocyclines, doxycycline, clindamycin and erythromycin were all below the breakpoint of antibiotic resistance. The patients with acne vulgaris with disease duration of more than 2 years documented higher MIC values in doxycycline, erythromycin, and clindamycin than those of less than 2 years. The patients who were previously treated with topical or systemic antibiotics showed higher MIC in doxycycline. Antibiotic resistance of P. acnes is still low in Korea, but at this point, there is an increasing trend of MIC. Caution and acknowledgement of increased risk of antibiotic resistant P. acnes should be advised in acne antibiotic treatment to minimize and avoid the emergence of the resistant strain.     

Detection of Propionibacterium acnes polypeptides which have stimulated an immune response in acne patients but not in normal individuals

Abstract Patient and normal volunteer sera were used as probes in two-dimensional PAGE of P. acnes culture supernatant fluid and cell extracts to determine whether specific P. acnes polypeptides were associated with the immune reaction in acne. Eight polypeptides, Mr 20 to 131 × 10³, pi 4.7 to 6.5 in the cell extract, and 7 polypeptides Mr 10 to 24 kD, pI 4.8 to 7.5 in the culture supernatant fluid were specifically highlighted by patient sera and not volunteer sera. These polypeptides were not related to described extracellular enzymes of P. acnes. It is possible that these polypeptides are involved in the induction of acne.     

Correlation between Propionibacterium acnes biotypes, lipase activity and rash degree in acne patients

We examined the possible correlation between biotypes of Propionibacterium acnes, lipase activity, and rash degree in acne patients. Among 5 P. acnes biotypes, P. acnes biotype 3 (B3) was the most common, followed by P. acnes biotypes 1, 2 and 4; P. acnes biotype 5 was not found. P. acnes B3 was isolated from more severe skin rashes than those of the other biotypes. Production of propionic acid (PA) and butyric acid (BA) by P. acnes B3 was higher than those by the other P. acnes biotypes. As the rash degree in acne patients was more severe, the production of PA and BA elevated. Although only a few P. acnes strains were examined in the present study, P. acnes B3 had the highest lipase activity and might have the greatest influence on skin rash in acne patients.     

Antibiotic resistance of microbial strains isolated from Korean acne patients

Over several decades, topical and systemic antibiotics have been the mainstay of treatment for acne vulgaris. The widespread and long‐term use of antibiotics in the treatment of acne has resulted in the spread of resistant bacterial strains and treatment failure. We aimed to examine the bacteriology of acne vulgaris and to evaluate its susceptibility to the antibiotics widely used for acne in Korea. We examined the species of bacteria aerobically and anaerobically isolated from 100 Korean acne patients. Among the bacteria isolated, Staphylococcus epidermidis (36 patients) was the most common, followed by Propionibacterium acnes (30 patients). Eleven strains of P. acnes (36.7%) and 25 strains of S. epidermidis (69.4%) were resistant to one or other of the antibiotics tested. A higher proportion of P. acnes isolates were resistant to clindamycin (30%) and erythromycin (26.7%), than to any other antibiotics tested (P = 0.0003). Some S. epidermidis isolates were resistant to tetracycline and doxycycline in addition to clindamycin and erythromycin. In the previous studies, few strains of P. acnes were found to be resistant to any of the antibiotics, but this study shows that antibiotic‐resistant strains have been increasing in Korea acne patients.     

Propionibacterium acnes resistance to antibiotics in acne patients

The minimal inhibitory concentration (MIC) of Propionibacterium acnes in seventy-five acne patients receiving long-term antibiotic therapy demonstrated the emergence of resistant strains. The mean MIC in thirty-three patients receiving long-term tetracycline was four to five times higher than that found in control groups of acne patients not receiving antibiotic therapy and controls free of acne. The average MIC for erythromycin was more than 100 times higher in those receiving long-term antibiotic therapy. In a second group of sixty-two patients, the clinical course and number of P. acnes were correlated with the presence of "resistant strains" defined as P. acnes with a tenfold increase in MIC to tetracycline or erythromycin. Patients with resistant strains had higher counts of P. acnes and clinically were not doing as well as those with sensitive strains.     

The antibiotic susceptibility of Propionibacterium acnes: a 15-year bacteriological study and retrospective evaluation

Propionibacterium acnes strains were isolated from the comedones of 46 acne patients, and their susceptibilities to penicillin G, ampicillin, erythromycin, clindamycin, tetracycline, doxycycline, minocycline, cephalexin and gentamycin were studied by examining their minimum inhibitory concentrations. Two additional standard strains were included in the study. In the results, differing antibiotic susceptibilities were found, and P. acnes strains were the most sensitive to erythromycin and clindamycin, followed by ampicillin and minocycline. The highest levels of resistance were observed against clindamycin, erythromycin and tetracycline. Non-resistant strains were detected only against minocycline. A comparison of these results with others obtained by similar studies in our department during the last 15 years showed a progressive tendency toward antibiotic resistance for Propionibacterium acnes, probably related to the systemic administration of antibiotics for the treatment of bacterial infections other than acne.     

Multicenter cross‐sectional observational study of antibiotic resistance and the genotypes of Propionibacterium acnes isolated from Chinese patients with acne vulgaris

Antibiotics are widely applied in management of acne vulgaris, which raises the issue of antibiotic resistance. Due to improper application and supervision of antibiotics, antibiotic resistance has become a serious problem in China. So, the efficacy of antimicrobial therapy in acne is unclear without an objective monitor of antibiotic resistance of Propionibacterium acnes. This cross‐sectional, multicenter observational study is aimed at understanding the status of antibiotic resistance in P. acnes, investigating the measures of acne management in China and analyzing the genotypes of antibiotic‐resistant strains of P. acnes. Altogether, 312 strains of P. acnes were collected from patients in five medical centers across central China 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 23S rRNA, 16S rRNA and erm(X). The predominant resistance occurred in macrolides and lincomycin with an overall resistance rate of 47.8%. The resistance to tetracyclines was scarce with only two cases identified. The emergence of minimum inhibitory concentration elevation for tetracyclines is associated with its application history (P < 0.005). The genotypes of the reported macrolide–lincosamide–streptogramin B resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist. The tetracyclines have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China.     

Resolution of inflammatory acne vulgaris may involve regulation of CD4+ T-cell responses to Propionibacterium acnes

BACKGROUND: Propionibacterium acnes has been strongly implicated in inflammatory acne. However, its role in the disease is unclear. It has been hypothesized that an immune response to P. acnes and/or P. acnes heat shock proteins (HSPs) may play a role in the pathogenesis of inflammatory acne. OBJECTIVES: To compare the cell-mediated immune response to P. acnes and HSPs in acne patients, nonacne controls and individuals with resolved acne. METHODS: The proliferative response of peripheral blood mononuclear cells (PBMC) from acne patients, resolved acne donors and healthy controls to P. acnes, P. acnes HSP60 and HSP70, and mycobacterial HSPs was assessed by lymphocyte transformation assay (LTA). The proliferative response of purified CD4+ T cells was further analysed by limiting dilution analysis (LDA). Contingency tables (G-test) were used to analyse the proportion of individuals in each group showing a positive proliferative response for LTA or data fitting single-hit kinetics for LDA. RESULTS: Analysis of stimulation of PBMC with P. acnes, P. acnes HSP60 and HSP70 in the LTA showed the proportion of positive responders to be independent of subject group. However, the proportion of acne patients with a positive response to mycobacterial HSPs was significantly higher than those for the other subject groups. Analysis of LDA data showed the proportion of resolved donors with responses to P. acnes fitting the single-hit kinetics model to be significantly lower than those of the other groups. There were no significant differences in responses to other antigens. CONCLUSIONS: The significantly lower proportion of resolved donors demonstrating a single-hit kinetics response to P. acnes by LDA may represent negative regulation of the CD4+ T-cell response to P. acnes in these subjects.     

Characterization of acne patients carrying clindamycin-resistant Cutibacterium acnes: A Japanese multicenter study

Use of antimicrobials for acne treatment is correlated with an increased occurrence of antimicrobial-resistant Cutibacterium acnes. To clarify the role of antimicrobial use on the resistance and to investigate the characteristics of resistant strains, we conducted a multicenter study in dermatological clinics frequently visited by new patients with acne vulgaris. We collected specimens in 264 acne patients and tested 164 C. acnes strains isolated from 164 patients visiting 13 dermatological clinics. Antimicrobial susceptibility testing showed that the rates of resistance for tetracyclines, macrolides and clindamycin were significantly higher in C. acnes strains isolated from patients using antimicrobials for acne treatment than patients not using them. In particular, clindamycin-resistant strains were frequently isolated from patients with older median age (≥24 years) and severe/moderate acne. After investigating the resistance mechanism of 15 high-level clindamycin-resistant strains, the transposable clindamycin resistance genes, erm(X) or erm(50), were detected in 14 strains. Using single-locus sequence typing for C. acnes, the strains with erm(X) or multidrug resistance plasmid pTZC1 coding erm(50) and tetracycline resistance gene tet(W) were classified into clade F, which were specifically isolated from Japanese patients with acne, except for one strain. Our data showed that patients’ information, such as antimicrobial use, age and acne severity, are valuable in estimating whether a patient carries antimicrobial-resistant C. acnes. Additionally, our results suggest that the clade F strains have a high risk of acquiring multidrug resistance.