Norihisa Noguchi

The prevalence of antimicrobial-resistant Cutibacterium acnes in acne patients has increased owing to inappropriate antimicrobial use. Commensal skin bacteria may play an important role in maintaining the balance of the skin microbiome by producing antimicrobial substances. Inhibition of Cu. acnes overgrowth can prevent the development and exacerbation of acne vulgaris. Here, we evaluated skin bacteria with anti-Cu. acnes activity. Growth inhibition activity against Cu. acnes was tested using 122 strains isolated from the skin of healthy volunteers and acne patients. Comparative genomic analysis of the bacterium with or without anti-Cu. acnes activity was conducted. The anti-Cu. acnes activity was confirmed by cloning an identified gene cluster and chemically synthesized peptides. Cu. avidum ATCC25577 and 89.7% of the Cu. avidum clinical isolates (26/29 strains) inhibited Cu. acnes growth. The growth inhibition activity was also found against other Cutibacterium, Lactiplantibacillus, and Corynebacterium species, but not against Staphylococcus species. The genome sequence of Cu. avidum showed a gene cluster encoding a novel bacteriocin named avidumicin. The precursor protein encoded by avdA undergoes post-translational modifications, supposedly becoming a circular bacteriocin. The anti-Cu. acnes activity of avidumicin was confirmed by Lactococcus lactis MG1363 carrying avdA. The C-terminal region of the avidumicin may be essential for anti-Cu. acnes activity. A commensal skin bacterium, Cu. avidum, producing avidumicin has anti-Cu. acnes activity. Therefore, avidumicin is a novel cyclic bacteriocin with a narrow antimicrobial spectrum. These findings suggest that Cu. avidum and avidumicin represent potential alternative agents in antimicrobial therapy for acne vulgaris.

Staphylococcus epidermidis , a major skin bacterium, can cause opportunistic infections. Use of antimicrobial agents against Cutibacterium acnes for acne treatment becomes a risk factor for emergence of antimicrobial-resistant skin bacteria. In this study, the impact of antimicrobial treatment of acne vulgaris on S. epidermidis antimicrobial resistance was assessed. A total of 344 S. epidermidis strains isolated from patients with acne vulgaris who visited hospital (165 strains) and dermatological clinics (179 strains), respectively, were analyzed. Except for doxycycline, the resistance rates were higher in strains isolated from patients who had used antimicrobials for acne treatment than in those isolated from patients who had not used antimicrobials. The prevalence rates of strains with erm (C) from patients who used macrolides and clindamycin (hospital, 78.0%; clinics, 61.3%) and those of strains with tet (M) from patients who used tetracyclines (hospital, 27.5%; clinics, 42.4%) were significantly higher than those of strains from patients who did not use antimicrobials ( p < 0.05). All strains with erm (A) (8/8) and 91.7% strains with erm (C) (156/170) showed high-level resistance to macrolides and clindamycin (MIC ≥256 μg/mL). Furthermore, almost all strains with tet (M) showed resistance to minocycline. Our results showed that the use of antimicrobials for acne treatment may lead to an increased prevalence of antimicrobial-resistant S. epidermidis . In particular, the emergence of minocycline-resistant strains with tet (M) owing to the use of tetracyclines (doxycycline and minocycline) is a critical issue. Appropriate antimicrobial use for acne treatment may be an important strategy to prevent the emergence of antimicrobial-resistant skin bacteria.

Pseudomonas aeruginosa is a major biofilm-forming, opportunistic pathogen. Tolerance to antimicrobial agents due to biofilm formation may lead to the emergence of antimicrobial-resistant bacterial strains. Thus, adjunctive agents that can inhibit biofilm formation are necessary to enhance the therapeutic efficacy of antimicrobial agents. In this study, we evaluated the anti-biofilm formation activity of selected Chinese herbal medicines and nutraceuticals, which are commercially available in Japan. Among the eight agents evaluated for their potential to inhibit biofilm formation, Eiekikaryu S, Iribakuga and Hyakujunro significantly reduced P. aeruginosa biofilm formation (P rhlR, rhlA and lasB) in P. aeruginosa was significantly suppressed by Eiekikaryu S, Iribakuga and Hyakujunro (P P. aeruginosa .

The increasing incidence of Haemophilus influenzae with decreased susceptibility to quinolones (quinolone low-susceptible H. influenzae ) in Japan has raised concerns about therapeutic failure. Thus, assessment of effective antimicrobial agents is necessary to establish an effective therapeutic strategy against resulting infections. In this study, in vitro bactericidal effects of quinolones on low-susceptible H. influenzae strains were evaluated using time-kill curve analysis. For tosufloxacin, log reduction values for low-susceptible strains were significantly lower than those for susceptible strains at both Cmax and 1/2 Cmax. Conversely, although the log reduction values were lower for susceptible strains, the Cmax of levofloxacin and β-lactams (amoxicillin and cefditoren) indicated bactericidal effects. In addition, higher concentrations of tosufloxacin at 2×Cmax and 4×Cmax had bactericidal effects on not only susceptible but also low-susceptible strains. These data strongly suggest that we should consider the presence of low-susceptible strains and reconsider the appropriate dosage of tosufloxacin for treatment, especially for paediatric patients.

The prevalence of antimicrobial‐resistant Cutibacterium acnes is an important concern for the antimicrobial treatment of acne vulgaris. We hypothesized that antimicrobial treatment regimens for acne vulgaris would change following the revisions in the Japanese acne treatment guidelines, which added a statement regarding appropriate antimicrobial usage. Here, we studied the changes in antimicrobial use and antimicrobial‐resistant C. acnes isolated from acne patients. A total of 127 C. acnes isolates collected from 212 patients with acne between 2013 and 2018 were used. Roxithromycin and clindamycin resistance rates were approximately 50% and 40%, respectively. In contrast, the prevalence of low doxycycline‐susceptible strains (minimum inhibitory concentration [MIC] ≥8 μg/mL) in 2018 (17.4%) was 5.6‐fold higher than that in 2013 (3.1%). Although the number of patients with severe and moderate acne did not change, the number of patients with a history of oral tetracycline use increased. The incidence of low doxycycline‐susceptible strains was high in patients with a history of oral tetracycline use. The prevalence of strains with a 16S rRNA mutation, which confers reduced susceptibility to tetracyclines, increased by 8.6‐fold (12.1%) from 2016 to 2018 in comparison with the previously revised guidelines (1.4%). Furthermore, the prevalence of low susceptibility strains with two resistance factors, 16S rRNA mutation and ribosomal S10 protein substitution, also increased. Approximately 10% of strains had the exogenous resistance gene, tet(W) (2013 to 2015, 10.1%; 2016 to 2018, 8.6%), and these strains showed different susceptibility to doxycycline dependent on the expression of tet(W) (MIC range 0.5–8 μg/mL). Our data show that the antimicrobial resistance pattern in C. acnes changes according to the trend of antimicrobial usage for acne treatment. Therefore, we should pay heed to the rapid dissemination of tetracycline resistance in C. acnes owing to acquisition of 16S rRNA mutation and tet(W).

Introduction. Empirical evidence suggests that Portulaca oleracea L. treats enteric infections, including dysentery, cholera, and acute infectious gastroenteritis. Aim. The aim of this study is to clarify the growth-inhibitory effects of Portulaca oleracea L. extract against 56 strains of intestinal pathogens. Methodology. ‘Gogyo-so-cha (GSC)’ was used as the P. oleracea L. formulation. A growth curve analysis was used to measure the growth-inhibitory effects of GSC, and Shiga toxin induction was measured using the latex agglutination test. Results. GSC demonstrated strong bactericidal effects against Shigella dysenteriae and Vibrio cholerae strains from various isolates. GSC demonstrated weak or no bactericidal effects against intestinal commensal bacteria, including Enterococcus spp. and Escherichia coli . GSC did not induce Shigella toxins. Conclusion. GSC significantly inhibited the growth of intestinal pathogens, including S. dysenteriae and V. cholerae , without adversely affecting the intestinal flora, supporting the usage of GSC in traditional Chinese medicine. Taken together, GSC would be of immense value in the developing world, where diarrhoeal infectious diseases continue to pose a major health risk.

Antimicrobial resistance (AMR) is a serious problem worldwide. We searched for the AMR determinants of various bacteria isolated from clinical settings and studied their resistance mechanisms and molecular epidemiology. This review focuses on the AMR of Staphylococcus aureus, a major gram-positive pathogen, which has the ability to acquire resistance to antimicrobials. The resistance factors of S. aureus are frequently found on mobile elements, including plasmids and transposons. We determined the complete DNA sequence of the tetracycline-resistance plasmid and found that the inducible expression of tetK in S. aureus was regulated by a post-transcriptional attenuation mechanism. Furthermore, outbreaks of methicillin-resistant S. aureus (MRSA) in hospitals and communities have led us to study infection controls, including the antiseptic susceptibility evaluation and molecular epidemiology of MRSA. Various antiseptic resistance determinants, such as qacA/B and smr, were identified on plasmids and characterized. We demonstrated that the plasmid-mediated efflux pump QacB variant QacIII confers fluoroquinolone efflux ability to S. aureus. Studies on MRSA epidemiology had shown that community-acquired MRSA (CA-MRSA) was disseminated into hospitals and that an increased use of alcohol-based rubs could reduce the incidence of MRSA infections in such institutions. Additionally, the study of CA-MRSA collected from communities and hospitals showed an increase in Panton-Valentine leucocidin (PVL)-positive CA-MRSA, causing severe skin and soft tissue infections. Moreover, various PVL-positive CA-MRSA clones have disseminated in Japan, whereas the USA300 LV/J clone evolved in that country. Our study provides important information regarding MRSA infection control.