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1.
In recent years, significant progress has been made in the understanding of the pathophysiological mechanisms of acne and the role of Propionibacterium acnes. With this review, the authors aim to provide an update on the current understanding of the role of P. acnes in the development of acne lesions and analysing the potential implications for future treatments. A total of 188 articles published between January 1980 and March 2013 were searched using key words such as acne, P. acnes, microbiology, Corynebacterium acnes, acne vulgaris, pathogenesis, antibiotic, vaccination and a combination of those key words. From those articles, 77 were analysed in depth. Recent data confirm that P. acnes has a strong proinflammatory activity and targets molecules involved in the innate cutaneous immunity, keratinocytes and sebaceous glands of the pilosebaceous follicle and leads to the development of comedones. Furthermore, the profile of its different strains may differ between healthy subjects and acne patients. The better understanding of the role of P. acnes may allow for new perspectives in the treatment of acne. Novel therapies should target molecules implicated in the activation of innate immunity, including toll‐like receptors, protease‐activated receptors and topical antimicrobial peptides; the latter may be an alternative to topical antibiotics and thus a solution for limiting bacterial resistance induced by topical macrolides. Vaccines may also be promising. However, the most appropriate candidate remains to be selected.  相似文献   

2.
Antimicrobial agents have been used for eradication of Cutibacterium (formerly Propionibacterium) acnes that is an exacerbation factor of the skin disease acne vulgaris. However, the use of antibiotics is associated with an increased risk of promoting the emergence of resistant bacteria and leading to skin dysbiosis. Traditional Japanese Kampo medicines, such as Keigairengyoto, are used to treat acne. However, there is incomplete understanding regarding their functional mechanism in treatment of acne. In this study, we examined the antimicrobial and anti‐lipase activity of the Kampo medicines used empirically for acne treatment. Three oral medicines, Keigairengyoto, Seijoboufuto and Jumihaidokuto, were found to inhibit the growth of C. acnes and decrease the lipase activity. Especially, Keigairengyoto caused remarkable decrease of bacterial lipase activity. Furthermore, topical medicines such as Shiunko and Chuoko significantly decreased the lipase activity in a dose‐dependent manner, without inhibiting C. acnes growth. The topical medicines were found to inhibit the expression of gehA, which codes for extracellular lipase. Our results indicate that Shiunko and Chuoko have potential as effective acne therapeutic agents, especially because they do not promote the emergence of antimicrobial‐resistant bacteria and skin dysbiosis.  相似文献   

3.
Background The increasing prevalence of antimicrobial resistance in Propionibacterium acnes poses a significant challenge to successful treatment outcomes in acne patients. Although P. acnes resistance has been demonstrated throughout the world, no previous data regarding the antimicrobial susceptibility of P. acnes in Colombia are available. Objectives The aim of this study was to determine the antimicrobial susceptibility of P.  acnes to common antibiotics used in the treatment of acne in a Colombian population. Methods Samples were collected from facial acne lesions of 100 dermatology patients. All samples were cultured in anaerobic conditions, and final identification of isolates was performed. Isolates of P. acnes were then subjected to antimicrobial susceptibility tests using erythromycin, clindamycin, tetracycline, doxycycline, and minocycline. Results Propionibacterium acnes isolates resistant to erythromycin (35%), clindamycin (15%), doxycycline (9%), tetracycline (8%), and minocycline (1%) were observed. Isolates with cross‐resistance were also observed (to erythromycin and clindamycin [12%] and to doxycycline and tetracycline [6%]). Overall, 46% of isolates taken from patients with a history of antibiotic use demonstrated resistance, whereas 29% of isolates taken from patients who had never used antibiotics demonstrated resistance. Conclusions Antimicrobial resistance in P. acnes in this Colombian population has a lower prevalence than those reported in Europe and follows a similar pattern to findings elsewhere in Latin America. Resistance is demonstrated even in isolates from patients with no previous history of antibiotic use. Resistance to erythromycin is most commonly observed. Minocycline emerges as the most effective antibiotic.  相似文献   

4.
Current acne treatments present several limitations, posing the need for new effective therapies for long-term administration for recalcitrant or relapsing acne. Key players in acne that may emerge as targets for future acne treatments include the cutaneous loss of diversity of Cutibacterium (formerly Propionibacterium) acnes phylotypes and the insulin-like growth factor-1 signalling pathway. New data about the loss of diversity of microbiota in acne provides the rationale for the potential use of oral or topical probiotics. Another therapeutic approach to modulate the microbiota could be topical formulation of Cacnes bacteriophages to target specifically the pathogenic ‘acnegenic’ Cacnes phylotypes. Insulin-sensitizing agents such as metformin, myo-inositol and d -chiro-inositol represent promising agents, but to date there have been only limited studies and much heterogeneity in the methods of assessing acne efficacy outcomes. Moving towards a holistic approach for patients with acne is the future, by taking into account both internal and external factors, such as pollution, stress, acne family history, age, smoking habits and diet, and addressing quality of life and the psychological impact of acne.  相似文献   

5.
Acne vulgaris is the most common disorder of the pilosebaceous unit leading to inflamed skin characterized by the formation of comedones, papules, pustules and scarring. There is increasing evidence that the abundance of Propionibacterium acnes (P. acnes) in the inflamed acne lesions triggers inflammation. Therefore, in addition to treatment with retinoids, the use of antimicrobial agents has been established as a treatment option for acne. This indicates that antimicrobial mechanisms to control the growth of P. acnes may have an important influence on the severity of inflammatory acne. One import antimicrobial innate defense system comprises the production of antimicrobial peptides (AMP), small molecules with a broad spectrum of antimicrobial activity as well as immunomodulatory properties. Although the role of AMP in acne is still emerging, there is increasing evidence that AMP may be of importance in acne. The aim of this viewpoint is to provide some hypotheses about the potential function of AMP in the pathogenesis of acne and to discuss potential AMP‐based therapies for the treatment of acne.  相似文献   

6.
Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S. epidermidis, from acne patients. A total of 92 and 87 S. epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin‐resistant S. epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high‐level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256 μg/mL) compared with methicillin‐susceptible S. epidermidis strains (2.7%, 3/111 strains) (< 0.01). The rate of levofloxacin resistance in C. acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S. epidermidis strains (= 0.93, < 0.01). The high‐level levofloxacin‐resistant strains were frequently found in patients with history of quinolone use compared with those without (< 0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C. acnes but also S. epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.  相似文献   

7.
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.  相似文献   

8.
The prevalence of antimicrobial‐resistant Propionibacterium acnes strains isolated from acne patients has been increasing in Japan. Here, to estimate the current resistance rate, we tested antimicrobial susceptibility among P. acnes from acne patients having visited a specialized dermatology clinic between 2013 and 2015. Rates of resistance to macrolides and clindamycin were 44.3 (31/70) and 38.6% (27/70), respectively. erm(X), which confers high‐level clindamycin resistance (minimum inhibitory concentration ≥256 μg/mL), was detected in six isolates, whereas no resistance determinants were identified in eight strains showing high‐level resistance to clindamycin. Using single‐locus sequence typing, the P. acnes isolates were classified into five clades (A, E, F, H and K), with all high‐level clindamycin‐resistant strains lacking known clindamycin resistance determinants being grouped together (in clade F). P. acnes isolates from patients previously treated with macrolides and clindamycin showed a macrolide resistance rate (55.3%) significantly higher than that of those from patients not having received these treatments (21.7%, P < 0.05). Furthermore, strains of clade F, which were very rarely isolated from healthy individuals, were more frequently recovered from patients with severe acne (40.0%) than those with mild acne (23.3%). Our data showed an increase in macrolide‐resistant P. acnes prevalence in Japan due to the use of antimicrobial agents for acne treatment. Furthermore, we identified strains of specific phylogenetic groups frequently associated with severe acne patients.  相似文献   

9.
Background Acne is a common chronic inflammatory dermatosis of the pilosebaceous unit. It is characterized by seborrhoea, comedone formation and an inflammatory response consistent with defective cellular immunity to Propionibacterium acnes. Objectives The objective of this study was to investigate the immune reactivity of patients with acne compared with healthy controls by examining the response of peripheral blood mononuclear cells (PBMCs) to stimulation with P. acnes. Particular focus was placed upon measuring the production of interleukin (IL)‐10, which has an established immunoregulatory role. Patients and methods Venous blood was collected from 47 patients with acne and 40 age‐ and sex‐matched healthy controls with no prior history of acne. PBMCs were cultured and their cytokine response to P. acnes investigated. Results Proinflammatory IL‐8 and tumour necrosis factor (TNF)‐α secretion from PBMCs was higher in patients with acne when stimulated with P. acnes. In contrast, a statistically significant reduction in PBMC secretion of anti‐inflammatory IL‐10 in patients with acne was identified. The impaired production of IL‐10 by PBMCs from patients with acne was confined to CD14+ cells presumed to be monocytes. The ability of CD14 cells from patients with acne to phagocytose P. acnes bacteria was also observed to be defective but the addition of exogenous IL‐10 to PBMC cultures restored phagocytic activity. Conclusions These data suggest that patients with acne have a proinflammatory cytokine milieu and crucially are unable to contain early inflammatory changes due to a specific defect in immunosurveillance, namely low monocyte IL‐10 production. Our observations raise the possibility that acne therapeutics might profitably target IL‐10 both as a regulator of proinflammatory cytokines and in augmenting the CD14+ cell phagocytic response.  相似文献   

10.
Background This NHS/HTA‐funded study aimed to rank five commonly used antimicrobial therapies for acne in order of their clinical effectiveness and cost‐effectiveness. We also wanted to identify which agents are less likely to promote resistance and those which are effective in patients who harbour high numbers of resistant Propionibacterium acnes strains. Methods From surgeries and colleges in the Nottingham and Leeds areas, 649 patients with mild to moderate facial acne were recruited. The two primary outcome measures were patient self‐assessment of improvement in overall acne severity and reduction in inflamed lesion count, measured at 18 weeks. Secondary outcome measures included two acne severity scores, assessors' global estimation of improvement, quality of life and utility scores, enumeration of antibiotic resistant propionibacteria, and the incidence of adverse events. Results and Conclusions The most effective treatments (percentage with at least moderate improvement according to patients, mean change in lesion count) were the topical Benzamycin® b.d. (66%, ? 27) and its components given separately (topical erythromycin o.d. + 5% benzoyl peroxide o.d.) (63%, ? 26), followed by 5% benzoyl peroxide b.d. (60%, ? 23). The least effective were oral oxytetracycline (55%, ? 18) and minocycline (54%, ? 22). The most cost‐effective treatment was benzoyl peroxide and least cost‐effective was minocycline. In terms of quality of life, benzoyl peroxide moved down the rankings and minocycline moved up. The two topical erythromycin‐containing regimens produced the largest reductions and the oral treatments the smallest in the prevalence and population density of cutaneous propionibacteria. Prior bacterial colonisation did not affect outcome in the topical groups. Efficacy of both oral preparations was influenced by tetracycline resistant P. acnes strains. Disclaimer The views and opinions expressed are those of the authors and do not necessarily reflect those of the Department of Health.  相似文献   

11.
Background Propionibacterium acnes is an important target in acne management. Antibiotic resistance has increased, reducing its clinical efficiency. Objective To study the prevalence, antimicrobial susceptibility patterns, and resistance mechanisms of P. acnes isolated from patients with acne. Methods Skin swabs were collected from 83 patients. Agar dilution determined the minimum inhibitory concentrations of five antibiotics. Polymerase chain reaction and DNA sequencing were used to identify mutations. Results P. acnes was isolated in 80 of 83 patients (96%), and 27 patients had resistance to antibiotics (33.7%). The mean age was older in the antibiotic‐resistant group (20.8 ± 5.8 vs. 18.3 ± 3.7, P = 0.02). Resistance to trimethoprim–sulfamethoxazole was 26.3%, erythromycin 12.5%, and clindamycin 7.5%. All clindamycin‐resistant strains had cross‐resistance to erythromycin, and 40% erythromycin‐resistant strains had cross‐resistance to trimethoprim–sulfamethoxazole. All strains were sensitive to tetracycline and doxycycline. The use of topical erythromycin or clindamycin was a risk factor to carry resistant strains (P = 0.02, P = 0.04, respectively). Resistance to trimethoprim–sulfamethoxazole was associated with acne severity (P = 0.02). Six of the 10 erythromycin‐resistant strains had a mutation in the peptidyl transferase region of the 23S rRNA gene: one A2058G and five A2059G. No strain carrying mutation G2057A was found. Conclusions Resistance to trimethoprim–sulfamethoxazole was the most common pattern found, and further studies are required to clarify its resistance mechanism. A certain tetracycline resistance was expected, but interestingly all strains remained sensitive. Resistance to erythromycin and clindamycin were influenced using topical formulations. Mutation A2059G was related to high resistance to erythromycin. Antibiotic resistance is increasing, and new strategies are needed.  相似文献   

12.
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14.
Acne is a chronic inflammatory illness of the pilosebaceous follicle where innate immunity plays a central role. In acne, the density of Propionibacterium acnes is increased in the pilosebaceous unit. We hypothesized that the severity of acne is not only dependent on the proliferation of P. acnes but also dependent on the pro‐inflammatory potential of P. acnes strains and consequently constitutes potential triggering factor for acne scarring. We investigated pro‐inflammatory potential of five different strains of P. acnes and P. avidum in skin explants and the preventive effect of zinc gluconate. The expression of immune markers was studied by immunohistochemistry, RT‐qPCR and ELISA. P. acnes strains modulate differently the expression of immune markers both at gene and at protein levels. P. acnes type III had the highest pro‐inflammatory potential by up‐regulating the expression of PAR‐2, TNF‐alpha, MMP‐13 and TIMP‐2, whereas P. avidum had the weakest by up‐regulating only MMP‐13 and TIMP‐2. Preincubation of zinc gluconate, which is a modulator of innate immunity, down‐regulates the expression of most immune markers induced by P. acnes, PAR‐2, TIMP‐2, up‐regulates MMP‐1, TIMP‐1. Our results demonstrate that different P. acnes strains have different inflammatory potential targeting markers of cutaneous innate immunity, and that inflammatory potential can be down‐regulated by zinc gluconate. As such, the inflammatory potential of P. acnes strains on acne skin may influence the severity of inflammatory acne lesions and scars.  相似文献   

15.
Abstract: The etiology of acne is a complex process, and acne is one of the most common skin disorders affecting millions of people. The pathogenesis of acne is closely associated with the bacterium, Propionibacterium acnes which was previously known as Corynebacterium parvum. Both viable and non‐viable P. acnes/C. parvum have been shown to induce an immunostimulatory effect in vivo, suggesting that even dead bacteria continue to activate an inflammatory response. Acne treatments with lasers or devices, induce a bactericidal effect through heat generation which may not address the immunogenic activity of P. acnes and the resulting acne inflammation. Therefore, we sought to determine whether killed P. acnes is capable of inducing an inflammatory response and therefore could be a contributing factor in acne. Direct heat treatment of P. acnes cultures with temperatures ranging from 50°C to 80°C reduced P. acnes viability. Both viable and heat‐killed P. acnes activated the p38 MAP kinase and its downstream substrate Hsp27. Stimulating keratinocytes with normal and heat‐inactivated P. acnes resulted in an induction of proinflammatory nitric oxide and IL‐8 production. Thus killed P. acnes is capable of inducing inflammation in skin suggesting that therapies that have both bactericidal and anti‐inflammatory effects may result in a more effective treatment of patients with acne than treatments that are bactericidal alone.  相似文献   

16.
Background: Inflammatory, medium to severe acne vulgaris is treated with systemic antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as well as the intrinsic anti‐inflammatory properties of these antibiotics. Although there are no correlations between the number of P. acnes and the severity of the disease, associations between the degree of humoral and cellular immune responses towards P. acnes and the severity of acne have been reported. Exact data on practical use of these compounds, such as differential efficacy or side effects are unavailable.A summary of currently available studies is presented. Methods: The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975, the summary of literature in English up to 1999, a systematic review of minocycline from 2002 as well as the data of randomized controlled studies published and listed in Medline thereafter were reviewed. Results: Tetracyclines [tetracycline 1 000 mg daily, doxycycline 100 (?200) mg daily, minocycline 100 (?200) mg daily, lymecycline 300 (?600) mg] and erythromycin 1 000 mg daily are significantly more effective than placebo in the systemic treatment of inflammatory acne.The data for tetracycline are best founded. Clindamycin is similarly effective. Co‐trimoxazole and trimethoprim are likely to be effective. Clear differences between the tetracyclines or between tetracycline and erythromycin cannot be ascertained. The data for the combination with topical treatments [topical benzoyl peroxide (BPO) or retinoids] suggest synergistic effects.Therefore systemic antibiotics should not be used as monotherapy. In case of similar efficacy, other criteria, such as pharmacokinetics (doxycycline, minocycline, lymecycline have longer half‐lives than tetracyclines), the rate of side‐effects (tetracycline: side effect‐rate ~4 % mild side effects; erythromycin: frequent gastrointestinal complaints; minocycline: rare, but potentially severe hypersensitivity reactions; doxycycline: dose‐dependent phototoxic reactions), the resistance rate [percentage of resistant bacteria higher with erythromycin (~ 50 %) than with tetracycline‐therapy (~ 20 %)], and the costs of therapy have to be taken into account. Conclusions: The systemic antibiotic therapy of widespread papulo‐pustular acne not amenable to a topical therapy is effective and well‐tolerated. In general therapy can be carried out for 3 months and should be combined with BPO to prevent resistance.  相似文献   

17.
Background Antibiotics have been used for more than 40 years against Propionibacterium acnes (P. acnes), the most common agent of acne. Antibiotic resistance to this bacterium becomes a worldwide problem in recent years. No studies are available on antibiotic susceptibility patterns of P. acnes among Egyptian acne patients. Objective To determine antibiotic susceptibility patterns of P. acnes isolated from acne patients attending the Dermatology outpatient clinic of an Egyptian university hospital to the most commonly prescribed antibiotics and to determine the difference in relation to age of patients, disease duration and previous antibiotic therapy for acne. Methods Cutaneous samples were obtained from pustular acne lesions on the face of 115 patients, which were cultured in anaerobic media to demonstrate the presence of P. acnes. Antibiotic susceptibility tests of isolated P. acnes were then performed to clindamycin, erythromycin, azithromycin, oxytetracycline and doxycycline by disk diffusion method. Results Propionibacterium acnes was isolated from 98 patients. Eighty‐nine isolates were susceptible to azithromycin, followed by doxycycline and oxytetracycline isolated from 82 and 72 patients respectively. Resistance of P. acnes to clindamycin was detected in 65 patients, followed by erythromycin in 48 patients. Comparing the antibiotic susceptibility patterns of P. acnes isolated from patients with and without previous antibiotic therapy for acne revealed statistically non‐significant differences as regards any of the antibiotics tested except for clindamycin and erythromycin. Statistically non‐significant differences existed between antibiotic susceptibility patterns of P. acnes to all tested antibiotics regarding age of patients (< or ≥20 years) and disease duration (< or ≥2 years). Conclusion Propionibacterium acnes in vitro susceptibility patterns differed among Egyptian patients to the commonly prescribed antibiotics with the highest to lowest resistance to clindamycin, erythromycin, oxytetracycline, doxycycline and azithromycin.  相似文献   

18.
Acne is known as a chronic inflammatory skin disease with sever adverse effects on quality of life in the patients. The increasing resistance to antibiotics has decreased their effectiveness in treating acne. As viable microbial dietary supplements, probiotics provide health benefits through fighting pathogens and maintaining the homeostasis of the gut and skin microbiome. The present article reviewed the potential of probiotics as beneficial microorganisms for treating acne vulgaris. This review of literature was conducted through a bibliographic search of popular databases, including Science Direct, PubMed, Scielo and Medline, using keywords such as probiotics, prebiotics, synbiotics, microbiome, and acne vulgaris to determine potential applications of these beneficial microbiomes in treating acne vulgaris. Acne lesions are associated with increases in proportion of Propionibacterium acnes as a skin commensal bacterium. The environmental studies showed inhibitory effects of probiotics on P. acnes, mediating by antibacterial proteins and bacteriocin‐like inhibitory substances, and their immunomodulatory effects onkeratinocytes and epithelial cells. Probiotics were also found to inhibit cytokine IL‐8 in epithelial cells and keratinocytes, suggesting immunomodulatory activities. Moreover, glycerol fermentation by Staphylococcus epidermidis was found to be a natural skin defense against acne and an overgrowth inhibitor of P. acnes. As an antimicrobial agent in lotions and cosmetic formulations, Lactococcus sp. can decrease the inflammatory mediators that are produced by P. acnes and cause vasodilation, edema, mast cell degranulation and TNF‐alpha release. Oral administration of probiotics was found to constitute an adjuvant therapy to conventional modalities for treating mild‐to‐moderate acne vulgaris.  相似文献   

19.
20.
Propionibacterium acnes (P. acnes), the sebaceous gland and follicular keratinocytes are considered the three actors involved in the development of acne. This exploratory study investigated the characteristics of the skin microbiota in subjects with acne and determined microbiota changes after 28 days of application of erythromycin 4% or a dermocosmetic. Skin microbiota were collected under axenic conditions from comedones, papulo‐pustular lesions and non‐lesional skin areas from subjects with mild to moderate acne according to the GEA grading using swabs. Samples were characterized using a high‐throughput sequencing approach that targets a portion of the bacterial 16S rRNA gene. Overall, microbiota samples from 26 subjects showed an overabundance of Proteobacteria and Firmicutes and an under‐representation of Actinobacteria. Staphylococci were more abundant on the surface of comedones, papules and pustules (P=.004 and P=.003 respectively) than on non‐lesional skin. Their proportions increased significantly with acne severity (P<.05 between GEA‐2 and GEA‐3). Propionibacteria represented less than 2% of the bacteria on the skin surface. At Day 28, only the number of Actinobacteria had decreased with erythromycin while the dermocosmetic decreased also the number of Staphylococci. A significant reduction (P<.05) from Day 0 of comedones, papules and pustules with no significant difference between the products was observed. The bacterial diversity on all sampling areas was similar. The dermocosmetic decreased the number of Actinobacteria and Staphylococcus spp. after 28 days. Staphylococcus remained the predominant genus of the superficial skin microbiota. No significant reduction in Staphylococcus spp. was observed with the topical antibiotic.  相似文献   

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