Antimicrobial-resistant
strains have emerged and disseminated throughout the world. The 23S rRNA mutation and
(X) gene are known as the major resistance determinants of macrolides and clindamycin in
...We isolated eight high-level macrolide-clindamycin-resistant
strains with no known resistance determinants, such as 23S rRNA mutation and
(X), from different acne patients in 2008 between 2013 and 2015. The aim of this study was to identify the novel mechanisms of resistance in
Whole-genome sequencing revealed the existence of a plasmid DNA, denoted pTZC1 (length, 31,440 bp), carrying the novel macrolide-clindamycin resistance gene
(50) and tetracycline resistance gene
(W). pTZC1 was detected in all
isolates (eight strains) exhibiting high-level macrolide-clindamycin resistance, with no known resistance determinants (MIC of clarithromycin, ≥256 μg/ml; clindamycin, ≥256 μg/ml). Transconjugation experiments demonstrated that the pTZC1 was horizontally transferred among
strains and conferred resistance to macrolides, clindamycin, and tetracyclines. Our data showed, for the first time, the existence of a transferable multidrug-resistant plasmid in
Increased prevalence of this plasmid will be a great threat to antimicrobial therapy for acne vulgaris.
Cutibacterium species such as C. acnes, C. avidum, and C. granulosum are known anaerobic skin inhabitants and often cause surgical site infections. These species are genetically similar and are ...difficult to identify rapidly. In addition, their pathogenicity and antimicrobial resistance remain unknown. In this study, antimicrobial resistance in Cutibacterium isolates was studied and a multiplex PCR method for their identification was developed.
A total of 497 C. acnes, 71 C. avidum, and 25 C. granulosum strains which were isolated from the acne pustule and infectious regions, were used.
The antimicrobial resistance rates of C. acnes, C. avidum, and C. granulosum strains isolated from patients with acne vulgaris were higher than those of strains isolated from patients with infectious diseases. In particular, macrolide-clindamycin-resistant strains were isolated most frequently from all species. Among the resistant strains, strains with 23S rRNA mutations were the most common in C. acnes (24.3%, 71/292), whereas C. avidum and C. granulosum strains were most frequently found with erm(X). For the first time, a C. granulosum strain carrying pTZC1, which codes erm(50) and tet(W), was isolated from patients with acne vulgaris. Regarding the rapid identification of causative pathogens from infectious regions, three Cutibacterium species were identified with 100% sensitivity and specificity using multiplex PCR method.
Our data showed that antimicrobial resistance differed among Cutibacterium species. The multiplex PCR method may contribute to the rapid detection of Cutibacterium species and selection of appropriate antimicrobial agents.
・Multidrug-resistant Cutibacterium species inhabit the skin.・Antimicrobial resistance levels differed among Cutibacterium species.・Multiplex PCR method was developed for rapid identification of Cutibacterium species.
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.
There have been very few studies on the prevalence and severity of acne scars in Japanese patients. The aim of the present study was to investigate the prevalence of acne scars and their impact on ...the quality of life (QOL) in Japanese acne patients. Acne scars were classified as mini-scars (atrophic scars of ≥0.5 and <2 mm in diameter) atrophic scars (≥2 mm in diameter), and hypertrophic scars. The severity of acne and acne scars were evaluated. The background of patients and their QOL in relation to acne were assessed. Of 240 subjects, 218 (90.8%) had scars. All patients with scars had mini-scars; 61.2% and 14.2% of 240 had atrophic scars and hypertrophic scars, respectively. Severe scarring was found in patients who had experienced severe acne symptoms, although 15.0% of patients with scars had experienced only mild acne symptoms. The total Dermatology Life Quality Index score was significantly higher in patients with scars than in patients without scars (5.9 ± 4.4 vs 4.2 ± 4.1). Almost all the patients had small atrophic scars with a diameter of 0.5 or more and less than 2 mm, which we have termed "mini-scars". Acne scars had a negative impact on patient QOL. Early initiation of treatment is recommended to avoid acne scars.
The Guidelines for the Treatment of Acne Vulgaris of the Japanese Dermatological Association was first published in Japanese in 2008 and revised in 2016 and 2017. These guidelines (GL) indicate the ...standard acne treatments in Japan and address pharmaceutical drugs and treatments applicable or in use in Japan. In these GL, the strength of the recommendation is based on clinical evidences as well as availability in Japanese medical institutions. In the 2016 and 2017 GL, some of the clinical questions were revised, and other questions were added in accordance with approval of topical medicines containing benzoyl peroxide (BPO). Rather than monotherapies of antibiotics, the 2017 GL more strongly recommend combination therapies, especially fixed-dose combination gels including BPO in the aspects of pharmacological actions and compliance in the acute inflammatory phase to achieve earlier and better improvements. The 2017 GL also indicate to limit the antimicrobial treatments for the acute inflammatory phase up to approximately 3 months and recommend BPO, adapalene, and a fixed-dose combination gel of 0.1% adapalene and 2.5% BPO for the maintenance phase to avoid the emergence of antimicrobial-resistant Propionibacterium acnes. The 2017 GL also discuss rosacea, which requires discrimination from acne and a different treatment plan.
Propionibacterium acnes and Staphylococcus epidermidis are normal skin inhabitants that are frequently isolated from lesions caused by acne, and these micro-organisms are considered to contribute to ...the inflammation of acne. In the present study, we examined the antimicrobial susceptibilities and resistance mechanisms of P. acnes and S. epidermidis isolated from patients with acne vulgaris in a university hospital in Japan from 2009 to 2010. Additionally, we analysed the relationship between the antimicrobial resistance of P. acnes and the severity of acne vulgaris. Some P. acnes strains (18.8 %; 13/69) were resistant to clindamycin. All strains had a mutation in the 23S rRNA gene, except for one strain that expressed erm(X) encoding a 23S rRNA methylase. Tetracycline-resistant P. acnes strains were found to represent 4.3 % (3/69) of the strains, and this resistance was caused by a mutation in the 16S rRNA gene. Furthermore, three strains with reduced susceptibility to nadifloxacin (MIC = 16 µg ml(-1)) were detected. When analysing the correlation between the antimicrobial resistance of P. acnes and S. epidermidis, more than 80 % of the patients who carried clindamycin-resistant P. acnes also carried clindamycin-resistant S. epidermidis. However, no epidemic strain that exhibited antimicrobial resistance was detected in the P. acnes strains when analysed by PFGE. Therefore, our results suggest that the antimicrobial resistance of P. acnes is closely related to antimicrobial therapy. Additionally, those P. acnes strains tended to be frequently found in severe acne patients rather than in mild acne patients. Consequently, the data support a relationship between using antimicrobial agents and the emergence of antimicrobial resistance.
A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, ...she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.
The efficacy of adapalene for acne treatment has been established. However, because of local adverse reactions, a fair number of patients discontinue adapalene treatment before experiencing its ...effects. To examine the usefulness of moisturizers concomitant with adapalene on adherence to treatment and its therapeutic effects in patients, 100 patients with mild to severe acne vulgaris were randomly assigned to one of two groups: group A, in which patients received adapalene in combination with a moisturizer (heparinoid); or group B, in which treatment consisted of adapalene alone and was converted to combination therapy with a moisturizer if local adverse reactions occurred that made adherence to treatment difficult. After 4 weeks of treatment, we compared the proportion of patients who adhered to therapy until the end of week 4, the number of treatment dropouts, and changes in the number of inflammatory eruptions and comedones between the groups. All of the patients in group A and 70% in group B continued the initial therapy until the end of week 4. In group B, three patients withdrew their consent and one patient stopped attending follow-up visits. The treatment period with the initial therapy was significantly elongated by the concomitant use of a moisturizer. No adverse effect of the use of a moisturizer was observed on the number of comedones and inflammatory eruptions. The concomitant use of a moisturizer with adapalene from the beginning of treatment did not affect its therapeutic effects and helped to improve adherence to treatment with adapalene.
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