The Anticancer Agent 3,3'-Diindolylmethane Inhibits Multispecies Biofilm Formation by Acne-Causing Bacteria and Candida albicans.

The Gram-positive anaerobic bacterium Cutibacterium acnes is a major inhabitant of human skin and has been implicated in acne vulgaris formation and in the formation of multispecies biofilms with other skin-inhabiting organisms like Staphylococcus aureus and Candida albicans. Indoles are widespread in nature (even in human skin) and function as important signaling molecules in diverse prokaryotes and eukaryotes. In the present study, we investigated the antibacterial and antibiofilm activities of 20 indoles against C. acnes. Of the indoles tested, indole-3-carbinol at 0.1 mM significantly inhibited biofilm formation by C. acnes without affecting planktonic cell growth, and the anticancer drug 3,3'-diindolylmethane (DIM) at 0.1 mM (32 µg/mL) also significantly inhibited planktonic cell growth and biofilm formation by C. acnes, whereas the other indoles and indole itself were less effective. Also, DIM at 0.1 mM successfully inhibited multispecies biofilm formation by C. acnes, S. aureus, and C. albicans. Transcriptional analyses showed that DIM inhibited the expressions of several biofilm-related genes in C. acnes, and at 0.05 mM, DIM inhibited hyphal formation and cell aggregation by C. albicans. These results suggest that DIM and other indoles inhibit biofilm formation by C. acnes and have potential use for treating C. acnes associated diseases. IMPORTANCE Since indoles are widespread in nature (even in human skin), we hypothesized that indole and its derivatives might control biofilm formation of acne-causing bacteria (Cutibacterium acnes and Staphylococcus aureus) and fungal Candida albicans. The present study reports for the first time the antibiofilm and antimicrobial activities of several indoles on C. acnes. Of the indoles tested, two anticancer agents, indole-3-carbinol and 3,3'-diindolylmethane found in cruciferous vegetables, significantly inhibited biofilm formation by C. acnes. Furthermore, the most active 3,3'-diindolylmethane successfully inhibited multispecies biofilm formation by C. acnes, S. aureus, and C. albicans. Transcriptional analyses showed that 3,3'-diindolylmethane inhibited the expressions of several biofilm-related genes including lipase, hyaluronate lyase, and virulence-related genes in C. acnes, and 3,3'-diindolylmethane inhibited hyphal formation and cell aggregation by C. albicans. Our findings show that 3,3'-diindolylmethane offers a potential means of controlling acne vulgaris and multispecies biofilm-associated infections due to its antibiofilm and antibiotic properties.

Effect of Tranexamic Acid against Staphylococcus spp. and Cutibacterium acnes Associated with Peri-Implant Infection: Results from an In Vitro Study.

Tranexamic acid (TXA) is extensively used in orthopedic surgery and traumatology as an antifibrinolytic agent to control intra- and postoperative bleeding and, therefore, indirectly, to reduce postsurgery infection rates. The hypothesis of an additional antibiotic effect against microorganisms associated with periprosthetic joint infection needs to be further evaluated. We aimed to assess whether TXA could reduce bacterial growth using an in vitro model. ATCC and clinical strains of staphylococci and Cutibacterium acnes were tested against TXA in both planktonic and sessile forms. We recorded the percent reduction in the following variables: log CFU/mL by microbiological culture, percentage of live cells by confocal laser scanning microscopy, and, additionally in sessile cells, metabolic activity by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. Variables were compared between groups using the Kruskal-Wallis test, and the results were reported as median (interquartile range [IQR]). Statistical significance was set at a P value of <0.05. Clinical significance was defined as a reduction of ≥25%. TXA at 50 mg/mL led to a slight reduction in CFU counts (4.5%). However, it was at 10 mg/mL that the reduction reached 27.2% and 33.0% for log CFU/mL counts and percentage of live cells, respectively. TXA was not efficacious for reducing preformed 24-h mature staphylococci and 48-h mature C. acnes biofilms, regardless of its concentration. TXA did not exert an antimicrobial effect against bacterial biofilms. However, when bacteria were in the planktonic form, it led to a clinically and statistically significant reduction in bacterial growth at 10 mg/mL. IMPORTANCE The possible use of TXA as an antibiotic agent in addition to its antifibrinolytic effect may play an important role in the prevention of prosthetic joint infection.

Synergistic combination of Sapindoside A and B: A novel antibiofilm agent against Cutibacterium acnes.

Sapindus saponins extracted from Sapindus mukorossi Gaertn. have been reported to exert antibacterial activity against Cutibacterium acnes (C. acnes). However, there are no reports about their potentials against its biofilm, which is a major contributor to the antibiotic resistance of C. acnes. This study aimed to investigate the synergistic antibiofilm activity and action of the combination of Sapindoside A and B (SAB) against C. acnes. SAB with sub-MICs significantly inhibited the early-formed and mature biofilm of C. acnes and decreased the adhesion and cell surface hydrophobicity (p < 0.05). Also, SAB greatly reduced the production of exopolysaccharide and lipase (p < 0.05), and the binding mode of SAB and lipase was predicted by molecular docking, via hydrogen bonds and hydrophobic interactions. Biofilm observed with electron microscopies further confirmed the high antibiofilm activity of SAB against C. acnes. Furthermore, a significant down-regulation of biofilm biosynthesis-associated genes was observed. The combination index explained the synergistic effects of SAB leading to the above results, and the contribution of SA was greater than that of SB. The current results showed that SAB had synergistic antibiofilm activity against C. acnes, and the Sapindoside A played a major role, indicating that SAB could be a natural antiacne additive against C. acnes biofilm-associated infections.

Facile Biofilm Penetration of Cationic Liposomes Loaded with DNase I/Proteinase K to Eradicate Cutibacterium acnes for Treating Cutaneous and Catheter Infections.

BACKGROUND: The biofilm produced by Cutibacterium acnes is a major infection threat for skin and implanted catheters. Nanoparticles provide a new approach to eradicate biofilms. The present study evaluated the capability of cationic liposomes loaded with DNase I (DNS) and proteinase K (PK) to remove preformed C. acnes biofilms. METHODS: DNS and PK were able to target and disassemble the biofilm by degrading extracellular polymer substances (EPS). Soyaethyl morpholinium ethosulfate (SME) was used to render a positive charge and enhance the antibacterial activity of the liposomes. RESULTS: The cationic liposomes containing enzymes yielded monodisperse nanovesicles ranging between 95 and 150 nm. The entrapment efficiency of the enzymes in the liposomes achieved a value of 67-83%. All liposomal formulations suppressed planktonic C. acnes growth at a minimum inhibitory concentration (MIC) equal to the free SME in the solution. The enzyme in the liposomal form inhibited biofilm growth much better than that in the free form, with the dual enzyme-loaded liposomes demonstrating the greatest inhibition of 54% based on a crystal violet assay. The biofilm-related virulence genes PA380 and PA1035 were downregulated by the combined enzymes in the liposomes but not the individual DNS or PK. Scanning electron microscopy (SEM) and confocal microscopy displayed reduced C. acnes aggregates and biofilm thickness by the liposomal system. The liposomes could penetrate through about 85% of the biofilm thickness. The in vitro pig skin permeation also showed a facile delivery of liposomes into the epidermis, deeper skin strata, and hair follicles. The liposomes exhibited potent activity to eliminate C. acnes colonization in mouse skin and catheters in vivo. The colony-forming units (CFUs) in the catheter treated with the liposomes were reduced by 2 logs compared to the untreated control. CONCLUSION: The data suggested a safe application of the enzyme-loaded cationic liposomes as antibacterial and antibiofilm agents.

Thymol-loaded PLGA nanoparticles: an efficient approach for acne treatment.

BACKGROUND: Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed. RESULTS: Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around - 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage. CONCLUSION: TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment.

Properties of Orthopaedic Cements Biomechanically Little Affected by Exceptional Use of Liquid Antibiotics.

OBJECTIVES: To specify the concentration of the liquid antibiotics to be added to polymethylmethacrylate (PMMA) and its impact on the quality of the spacer is the purpose of this study with liquid clindamycin added to different cements. METHODS: In the present study, eight different cement mixtures were prepared and investigated. In the following, number 1 indicates the references, 2 all cements after liquid clindamycin was added to the liquid cement compound, 3 all cements after liquid clindamycin was added to the cement powder, and 4 all cements after liquid clindamycin was added to the cement dough. After curing, cements were filled into metal moulds and a pressure of 3 bar was maintained for 30 min. Mechanical investigations were carried out according to ISO 5833 (2002) and DIN 53435 (2007). For microbiological tests, standardized cylindrical mouldings (diameter: 25 mm, height: 10 mm) were produced and incubated in 10 ml buffer solution at room temperature for 24 h. All eluates were generated by spreading previously established suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes and methicillin-resistant Staphylococcus aureus (MRSA) with a 0.5 McFarland turbidity standard. RESULTS: Apparently, we found that in all investigated cases, the admixture of liquid antibiotic negatively affected the mechanical characteristics of the cement mould. Among the various test groups, the influence on the ISO compression strength and ISO flexural modulus of the investigated test groups was only minimal when liquid clindamycin was added to cement liquid. Compared to admixing of liquid clindamycin into cement powder or dough ISO compression strength and ISO flexural modulus and flexural strength showed the maximum reduction. The efficacy against chosen germs was reduced as well when liquid antibiotic was admixed instead of powder. This admixture of liquid anti-infective agents resulted in a 234% enhanced elution after 10 days 29 a negative effect on the inhibition zones were detected during the previous period. CONCLUSION: The admixture of powdery antibiotic is preferable to liquid antibiotics. If no powdery antibiotic is available, we can recommend the admixture of liquid antibiotic to liquid cement prior to dough production in case powdery antibiotics cannot be used. However, we discourage the admixture of liquid antibiotic to cement powder or cement dough during early low viscose phase.

Insights into the mechanism of Cymbopogan martinii essential oil in topical therapy of acne vulgaris.

Aim: The present study investigated the essential oil of Cymbopogan martinii (palmarosa oil; PRO) as a potential topical therapy in acne vulgaris. Materials & methods: GC-MS profiling and biocompatibility studies of PRO were undertaken. The antimicrobial potential was assessed against Cutibacterium acnes. anti-inflammatory, antityrosinase activity and lipid peroxidation were also evaluated. Results: Geraniol was identified as the major phytoconstituent, and the oil was found to be safe for topical application. The minimum inhibitory concentration and minimum bactericidal concentration values were noted as 16 µl/ml. PRO reduced the cytokine levels of TNF-α, IL-12 and IL-8 and inhibited tyrosinase. A low concentration of the oil (up to 0.5 µl/ml) produced malondialdehyde levels equivalent to that of untreated cells. Conclusion: PRO may prove useful as a natural topical agent in the management of acne.

Lay abstract Acne vulgaris is a highly prevalent skin condition among adolescents, associated with much psychological distress in the affected individuals. The disease primarily affects the hair follicles and sebaceous glands of the face, neck, chest and back. Hormonal imbalance leads to increased production of sebum. Abnormal cellular processes cause swelling of the follicles and create an environment that is conducive to the growth of Cutibacterum acnes. The bacteria are known to initiate an immune response, rupturing the wall of hair follicles and dispersing the contents into the surrounding skin tissues. Inflammation occurs, further laying the ground for skin blemishes. Although a number of drugs are reported for the topical management of this condition, they do not address all the factors contributing to the development of acne lesions and are also reported to have several adverse effects. Therefore, the existing drugs do not offer a satisfactory solution to the problem. The growing bacterial resistance to antimicrobial drugs is another cause of concern. An agent that effectively counters the various causative factors of acne, is safe for application on human skin and is devoid of the risk of bacterial resistance, would be an ideal anti-acne agent. In this study, the essential oil derived from the plant Cymbopogan martinii (palmarosa oil) was evaluated for its potential to inhibit the growth of C. acnes, and control inflammation and blemishes associated with acne. It was also checked for its compatibility with human skin. The results were promising, advocating the essential oil as a natural and holistic solution for treating acne.

Effects of Ulva sp. Extracts on the Growth, Biofilm Production, and Virulence of Skin Bacteria Microbiota: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes Strains.

Ulva sp. is known to be a source of bioactive compounds such as ulvans, but to date, their biological activity on skin commensal and/or opportunistic pathogen bacteria has not been reported. In this study, the effects of poly- and oligosaccharide fractions produced by enzyme-assisted extraction and depolymerization were investigated, for the first time in vitro, on cutaneous bacteria: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes. At 1000 µg/mL, poly- and oligosaccharide fractions did not affect the growth of the bacteria regarding their generation time. Polysaccharide Ulva sp. fractions at 1000 µg/mL did not alter the bacterial biofilm formation, while oligosaccharide fractions modified S. epidermidis and C. acnes biofilm structures. None of the fractions at 1000 µg/mL significantly modified the cytotoxic potential of S. epidermidis and S. aureus towards keratinocytes. However, poly- and oligosaccharide fractions at 1000 µg/mL induced a decrease in the inflammatory potential of both acneic and non-acneic C. acnes strains on keratinocytes of up to 39.8%; the strongest and most significant effect occurred when the bacteria were grown in the presence of polysaccharide fractions. Our research shows that poly- and oligosaccharide Ulva sp. fractions present notable biological activities on cutaneous bacteria, especially towards C. acnes acneic and non-acneic strains, which supports their potential use for dermo-cosmetic applications.

Potent in vitro synergistic antibacterial activity of natural amphiphilic Sapindoside A and B against Cutibacterium acnes with destructive effect on bacterial membrane.

Sapindus saponins are obtained from the outer bark of Sapindus mukorossi Gaertn. (S. mukorossi), and they have become an interesting subject in the search for new anti-acne agents without resistance. This study aimed to screen the synergistic antibacterial combination from Sapindus saponins and investigated the synergistic antibacterial action via targeting the cell membrane of Cutibacterium acnes (C. acnes) to reduce the effective dose. The combination of Sapindoside A and B (SAB) was obtained with synergistic activity against C. acnes. SAB led to the leakage of ions and disturbed the membrane morphology of C. acnes. The spectral features of cell membrane composition showed obvious changes based on Raman spectroscopy, and changes in membrane protein microenvironment were also observed by fluorescence spectroscopy. Among the above results, the contribution of Sapindoside A was greater than that of Sapindoside B to the synergistic combination of SAB. Furthermore, molecular docking demonstrated that Sapindoside A interacted with penicillin-binding protein 2, playing an important role in peptidoglycan synthesis for the cross wall, and showed a higher binding score than Sapindoside B, further indicating that the greater contribution in the synergistic action of SAB on membrane proteins. Collectively, these results showed that the synergistic antibacterial action of SAB against C. acnes could be achieved by attacking cell membrane, and Sapindoside A played a major role, suggesting that SAB has the potential to be the natural anti-acne agent additive in the cosmetic industry.

Efficacy of common antiseptic solutions against clinically relevant microorganisms in biofilm.

AIMS: Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. METHODS: We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. RESULTS: With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater reductions in nascent MRSA biofilms (logarithmic reduction (LR) = 3.12; p < 0.001) compared to other solutions. Bactisure treatment had the greatest reduction of mature Pseudomonas aeruginosa biofilms (LR = 1.94; p = 0.032) and a larger reduction than Vashe or Irrisept for mature Staphylococcus epidermidis biofilms (LR = 2.12; p = 0.025). Pooled data for all biofilms tested resulted in Bactisure and Povidone-iodine with significantly greater reductions compared to Vashe, Prontosan, and Irrisept solutions (p < 0.001). CONCLUSION: Treatment failure in PJI is often due to failure to clear the biofilm; antiseptics are often used as an adjunct to biofilm clearance. We tested irrigants against clinically relevant microorganisms in biofilm in vitro and showed significant differences in efficacy among the different solutions. Further clinical outcome data is necessary to determine whether these solutions can impact PJI outcome in vivo. Cite this article: Bone Joint J 2021;103-B(5):908-915.

Bacterial pericarditis and empyema caused by Cutibacterium acnes in a patient with metastatic lung cancer.

Bacterial pericarditis and empyema due to Cutibacterium acnes has rarely been reported. C.acnes, a normal component of human skin flora, is often considered a contaminant when isolated from body fluids and thus cases may be underreported. We report the first case of concurrent purulent pericarditis and empyema caused by C. acnes in a patient with newly diagnosed metastatic lung cancer. Our patient underwent pericardial window creation and placement of pericardial and bilateral chest tubes and was successfully treated with culture directed antibiotic therapy.

Zinc(II) Complexes of Amino Acids as New Active Ingredients for Anti-Acne Dermatological Preparations.

Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc-amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability.

Cutibacterium avidum resists surgical skin antisepsis in the groin-a potential risk factor for periprosthetic joint infection: a quality control study.

BACKGROUND: The skin commensal Cutibacterium avidum has been recognized as an emerging pathogen for periprosthetic joint infections (PJI). One currently assumes that the early occurring PJIs are a consequence of skin commensals contaminating the peri-implant tissue during surgery. We addressed whether standard skin antisepsis with povidone-iodine/alcohol before total hip arthroplasty (THA) is effective to eliminate colonizing bacteria with focus on C. avidum. METHODS: In a single-center, prospective study, we screened all patients for skin colonizing C. avidum in the groin before THA. Only in the patients positive for C. avidum, we preoperatively repeated skin swabs after the first and third skin antisepsis and antibiotic prophylaxis. We also obtained dermis biopsies for microbiology and fluorescence in situ hybridization (FISH). RESULTS: Fifty-one out of 60 patients (85%) were colonized on the skin with various bacteria, in particular with C. avidum in 12 out of 60. Skin antisepsis eliminated C. avidum in eight of ten (20%) colonized patients undergoing THA. Deeper skin (dermis) biopsies were all culture negative, but FISH detected single positive ribosome-rich C. avidum in one case near sweat glands. CONCLUSION: Standard skin antisepsis was not effective to completely eliminate colonizing C. avidum on the skin in the groin of patients undergoing THA. Colonizing with C. avidum might pose an increased risk for PJI when considering a THA. Novel more effective antisepsis strategies are needed. Trial registration No clinical trial.

Characterization of the human skin resistome and identification of two microbiota cutotypes.

BACKGROUND: The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity. RESULTS: In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria ("superbugs") existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such "cutotypes" was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development. CONCLUSIONS: The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome. Video abstract.

Hydrogen Peroxide Does Not Significantly Reduce Cutibacterium acnes Suture Contamination in Arthroscopic Rotator Cuff Repair.

PURPOSE: To evaluate the efficacy of application of the 3% hydrogen peroxide (HP)-soaked gauze as an addition to the standard preoperative sterile skin preparation for Cutibacterium acnes suture contamination in arthroscopic rotator cuff repairs. METHODS: A prospective randomized study was undertaken to evaluate 151 consecutive patients undergoing arthroscopic rotator cuff repair. Each shoulder was prepared with 1 of the 2 randomly selected protocols: chlorhexidine alcohol (1% chlorhexidine gluconate in 70% isopropyl alcohol)(control group) and chlorhexidine alcohol with 3% HP (HP-treated group). In the HP-treated group, the 3% HP-soaked gauze was applied over the shoulder for 5 minutes before the application of the chlorhexidine-alcohol. The first cut-tails of the anchor suture after cuff fixation were submitted to aerobic and anaerobic cultures. Patients were clinically evaluated for infection 10 days, 28 days, 3 months, 6 months, and 12 months after surgery. RESULTS: The rate of C acnes-positive cultures was 13.0% (10 of 77 cases) in the control group and 6.8% (5 of 74 cases) in the HP-treated group. The HP-treated group showed a trend of lower C acnes-positive culture rate, which did not reach statistical significance (relative risk, 0.52; 95% confidence interval, 0.19 and 1.45; number needed to treat, 16.1; P = .20). One case of coagulase-negative Staphylococcus (Staphylococcus intermedius) was isolated in the HP-treated group (1 of 74 cases, 1.3%). No other bacteria were isolated. No infections occurred in any of the patients treated in this study during the minimum 3-month follow-up period. One patient in the HP-treated group complained of skin irritation. CONCLUSIONS: The use of a 3% HP-soaked gauze as an addition to the standard preoperative sterile skin preparation for arthroscopic rotator cuff repairs showed only a marginal effect (statistically insignificant) in reducing the C acnes suture contamination rate in the arthroscopic rotator cuff repair patients. LEVEL OF EVIDENCE: I, prospective, randomized trial.

ARTICLE: A Novel Antibiotic Just for Acne.

Dermatologists consistently rank as the most frequent prescribers of systemic antibiotics, and one of the most common diagnoses for which we recommend these agents is acne vulgaris. Up to three quarters of the antibiotics that dermatologists prescribe are in the tetracycline class.1 Even though dermatology as a specialty is well-known for off-label prescribing, it may be surprising to note that no systemic antibiotic had been FDA approved solely for treatment of acne—until recently.

Oral Tetracyclines and Acne: A Systematic Review for Dermatologists.

Oral tetracyclines are the most widely prescribed systemic antibiotic for acne. Synthesis of efficacy and safety of traditional and novel oral tetracyclines is highly informative to clinical practice. We conducted a systematic search of PubMed to identify large interventional and observational studies utilizing oral tetracyclines as an acne treatment. We identified 13 articles meeting inclusion for this review, which represented 226,019 pediatric and adult acne patients. Oral tetracyclines that were included in this systematic review were sarecycline (a novel narrow-spectrum tetracycline), doxycycline, minocycline, and tetracycline. Based on shared and divergent outcome measures, different oral tetracyclines were variably effective against facial acne. Sarecycline also demonstrated efficacy in truncal acne. Members of the oral tetracycline class also differed in their ability to minimize antibiotic resistance and gut dysbiosis. J Drugs Dermatol. 2020;19:11(Suppl):s4-11.

Formulation of Creams Containing Spirulina Platensis Powder with Different Nonionic Surfactants for the Treatment of Acne Vulgaris.

Natural products used in the treatment of acne vulgaris may be promising alternative therapies with fewer side effects and without antibiotic resistance. The objective of this study was to formulate creams containing Spirulina (Arthrospira) platensis to be used in acne therapy. Spirulina platensis belongs to the group of micro algae and contains valuable active ingredients. The aim was to select the appropriate nonionic surfactants for the formulations in order to enhance the diffusion of the active substance and to certify the antioxidant and antibacterial activity of Spirulina platensis-containing creams. Lyophilized Spirulina platensis powder (SPP) was dissolved in Transcutol HP (TC) and different types of nonionic surfactants (Polysorbate 60 (P60), Cremophor A6:A25 (CR) (1:1), Tefose 63 (TFS), or sucrose ester SP 70 (SP70)) were incorporated in creams as emulsifying agents. The drug release was evaluated by the Franz diffusion method and biocompatibility was tested on HaCaT cells. In vitro antioxidant assays were also performed, and superoxide dismutase (SOD) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays were executed. Antimicrobial activities of the selected compositions were checked against Staphylococcus aureus (S. aureus) and Cutibacteriumacnes (C. acnes) (formerly Propionibacterium acnes) with the broth microdilution method. Formulations containing SP 70 surfactant with TC showed the most favorable dissolution profiles and were found to be nontoxic. This composition also showed significant increase in free radical scavenger activity compared to the blank sample and the highest SOD enzyme activity was also detected after treatment with the cream samples. In antibacterial studies, significant differences were observed between the treated and control groups after an incubation time of 6 h.

(+)-Erythro-Δ8'-7S,8R-Dihydroxy-3,3',5'-Trimethoxy-8-O-4'-Neolignan, an Anti-Acne Component in Degreasing Myristica fragrans Houtt.

Acne is a common skin condition observed in adolescents. Nutmeg (Myristica fragrans Houtt) (MF) is a well-known traditional Chinese medicine; its major toxic components, safrole and myristicin, are rich in essential oils. Essential oils of MF (MFO) were extracted by hydrodistillation; the residue was extracted using 50% methanol (MFE-M). The minimum inhibitory concentration (MIC) of MFE-M against Cutibacterium acnes and Staphylococcus aureus was 0.64 mg. Four compounds were obtained from MFE-M: myristicin (1), (+)-erythro-Δ8'-7S,8R- dihydroxy-3,3,5'-trimethoxy-8-O-4'-neolignan (2), (+)-erythro-Δ8'-7-hydroxy-3,4,3',5'-tetramethoxy 8-O-4-neolignan (3), and erythro-Δ8'-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (4). Compound 2 exerted the strongest antimicrobial activity, with MICs of 6.25 and 3.12 µg/mL against C. acnes and S. aureus, respectively. Moreover, 2 inhibited NO, PGE2, iNOS, and COX-2 levels in RAW 264.7 cells induced by LPS or heat-killed C. acnes; NO production at 50% inhibitory concentrations (IC50) was 11.07 and 11.53 µg/mL, respectively. Myristicin and safrole content was higher in MFO than in MFE-M. MFO and MFE-M caused no skin irritation after a single topical application in Wistar rats. MFE-M, with low safrole and myristicin content, did not cause skin irritation and exhibited an anti-acne effect; moreover, 2 was identified as the active substance. Therefore, MFE-M could be employed to develop anti-acne compounds for use in cosmetics.

Inhibitory Effects of a Sargassum miyabei Yendo on Cutibacterium acnes-Induced Skin Inflammation.

Acne vulgaris is a chronic inflammatory condition of skin sebaceous follicles. To explore its effects on acne vulgaris, we investigated the antibacterial and anti-inflammatory activities of Sargassum miyabei Yendo (a brown alga) ethanolic extract (SMYEE) on Cutibacterium acnes (C. acnes)-stimulated inflammatory responses, both in vivo and in vitro. To induce inflammation in vivo, C. acnes was intradermally injected into the dorsal skin of mice, to which SMYEE was applied. The antimicrobial activity of SMYEE was evaluated by the determination of minimum inhibitory concentrations (MICs). To explore in vitro anti-inflammatory effects, HaCaT cells were stimulated with C. acnes after treatment with SMYEE. The levels of IL-8 and the underlying molecular effects in C. acnes-stimulated HaCaT cells were assessed by enzyme-linked immunosorbent assay, Western blotting, and an electrophoretic mobility shift assay. Mouse skin lesions improved after treatment with SMYEE (50 µg/mouse). Neutrophil infiltration was significantly reduced in SMYEE-treated compared to SMYEE-untreated skin lesions. SMYEE reversed the C. acnes-induced increase in IL-8 levels in HaCaT cells and suppressed dHL-60 cell migration. SMYEE also inhibited C. acnes-induced phosphorylation of the extracellular signal-regulated kinase and inhibited activator protein-1 signaling. SMYEE may be a useful treatment for C. acnes-induced acne vulgaris.