A break-even analysis of benzoyl peroxide and hydrogen peroxide for infection prevention in shoulder arthroplasty.

BACKGROUND: Newer strategies to decolonize the shoulder of Cutibacterium acnes may hold promise in minimizing the occurrence of infections after shoulder arthroplasty, but little is known about their cost-effectiveness. Break-even models can determine the economic viability of interventions in settings with low outcome event rates that would realistically preclude a randomized clinical trial. We used such modeling to determine the economic viability of benzoyl peroxide and hydrogen peroxide for infection prevention in shoulder arthroplasty. METHODS: Skin decolonization protocol costs ($11.76 for benzoyl peroxide; $0.96 for hydrogen peroxide), baseline infection rates for shoulder arthroplasty (0.70%), and infection-related care costs ($50,230) were derived from institutional records and the literature. A break-even equation incorporating these variables was developed to determine the absolute risk reduction (ARR) in the infection rate to make prophylactic use economically justified. The number needed to treat was calculated from the ARR. RESULTS: Topical benzoyl peroxide is considered economically justified if it prevents at least 1 infection out of 4348 shoulder arthroplasties (ARR = 0.023%). Hydrogen peroxide is economically justified if it prevents at least 1 infection out of 50,000 cases (ARR = 0.002%). These protocols remained economically viable at varying unit costs, initial infection rates, and infection-related care costs. CONCLUSIONS: The use of topical benzoyl peroxide and skin preparations with hydrogen peroxide are highly economically justified practices for infection prevention in shoulder arthroplasty. Efforts to determine drawbacks of routine skin decolonization strategies are warranted as they may change the value analysis.

An update on formulation strategies of benzoyl peroxide in efficient acne therapy with special focus on minimizing undesired effects.

Benzoyl peroxide (BPO) in the form of over the counter monotherapeutics or prescription-only combinations is a key component of topical acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. Various galenic approaches have been pursued to resolve this ambivalence, but only a few have managed to enter the market. This article aims to give a comprehensive overview of the published experimental vehicle systems and to identify the fundamental rationales. With regard to the formulation, an increase in the tolerability of BPO can essentially be achieved by combining BPO with re-fattening and moisturizing substances, by incorporating it and controlling its release, as well as by targeted deposition of the active ingredient at the site of action, i.e. drug targeting. Recently, novel particulate formulations have been proposed that combine several of these design principles and are expected to bring new developments in this dynamic field of research.

Benzoyl peroxide use transiently decreases Cutibacterium acnes load on the shoulder.

BACKGROUND: Cutibacterium acnes is the most common pathogen in shoulder prosthetic joint infections. Short-contact benzoyl peroxide (BPO) solutions effectively reduce C acnes loads on the shoulder preoperatively. It is unknown how long the effect of BPO lasts. We evaluated C acnes counts 1 week after BPO application. We hypothesized that BPO would decrease C acnes burden with a rebound after 1 week. METHODS: Screening of 102 healthy volunteers with no history of shoulder surgery or C acnes infection was performed to establish bacterial counts. Thirty-four participants were selected based on an established threshold. Each was given BPO 5% for 3 consecutive days of application on either the left or right shoulder as indicated by a random number generator. Deep sebaceous gland cultures were obtained with a detergent scrub technique before BPO application, after 3 days of use, and 1 week after BPO treatment commenced. RESULTS: The differences between the logarithmic reduction and the logarithmic rebound at the anterior, lateral, and posterior sites were statistically significant. Anteriorly, the average log reduction was -0.44 and the average log rebound was 0.69 (P = .003). Laterally, reduction was -0.64 and rebound was 0.74 (P = .003). Posteriorly, reduction was -0.63 and rebound was 0.78 (P = .008). At the axilla, reduction was -0.40 and rebound was 0.31 (P = .10). The differences in C acnes burden between pretreatment and 1-week counts at all sites were not statistically significant. CONCLUSION: A significant decrease in C acnes burden occurred after BPO application but was not permanent. Significant rebound occurred just 1 week later.

Topical application of phenolic compounds suppresses Propionibacterium acnes-induced inflammatory responses in mice with ear edema.

Acne vulgaris (AV), a severe chronic inflammatory dermatosis, commonly treated with systemic or topical antibiotics that exacerbate bacterial resistance and pose adverse side effects, new approaches for suppressing or reducing Propionibacterium acnes-induced inflammatory responses and thereby treating AV remain necessary. In response, the goal of our study was to investigate the therapeutic potential of phenolic compounds in the in vivo inflammatory process induced by P. acnes. Mice were intradermally challenged with a suspension containing 1.0 × 107 CFU/mL of P. acnes per ear, after which groups of mice were variously treated with 20 µg of resveratrol, quercetin, gallic acid, or benzoyl peroxide. Mice ears were measured (mm) before each inducement and treatment. At the end of the experiment, activity catalase and superoxide dismutase, levels of myeloperoxidase (MPO), interleukin-1 beta (IL-1ß), tumor necrosis factor alpha, thiobarbituric acid reactive substances (TBARS), and glutathione were evaluated. Mice treated with resveratrol, quercetin, or gallic acid produced a 40%, 40%, and 30% reduction of the edema, respectively, while mice treated with resveratrol or gallic acid produced a 50 and 45% reduction in IL-1ß, also respectively, and a 35% reduction in MPO. Compared to mice in the control group (210 ± 21 µmol/mg protein) and ones treated with benzoyl peroxide (339.7 ± 21.3 µmol/mg protein), mice treated with resveratrol, quercetin, or gallic acid showed low levels of TBARS (71 ± 12 µmol/mg, 62 ± 10 µmol/mg, and 104 ± 15 µmol/mg protein, respectively). Such results suggest that phenolic compounds are a good alternative for the development of cosmetics that can be used to treat AV. Graphical abstract ᅟ.

Benzoyl Peroxide Inhibits Quorum Sensing and Biofilm Formation by Gardnerella vaginalis 14018.

Infection recurrence and antibiotic resistance of bacterial vaginosis-associated pathogenic biofilms underline the need for novel and effective treatment strategies. In this study, we evaluated the antimicrobial, antibiofilm, and quorum sensing inhibitory effects of benzoyl peroxide and salicylic acid against Gardnerella vaginalis ATCC 14018, the predominant pathogen of bacterial vaginosis. While the highest tested concentrations of 250 and 125 µg/mL for both compounds were not sufficient in completely inhibiting the growth of G. vaginalis ATCC 14018, they did prevent biofilm formation by inhibiting the bacterial quorum sensing system in the pathogen. To our knowledge, this report is the first evidence that benzoyl peroxide can have a quorum sensing-mediated biofilm controlling effect, as demonstrated using subinhibitory concentrations of this compound in order to reduce the cost, dosage, and negative side effects associated with current antimicrobial treatments.

Clinical evidence for washing and cleansers in acne vulgaris: a systematic review.

PURPOSE: Washing and over-the-counter cleansers are common interventions in acne vulgaris (AV), but the clinical evidence for their benefit is poorly understood. This systematic review presents clinical studies of washing and cleanser efficacy in acne vulgaris to guide treatment recommendations of dermatologists. MATERIALS AND METHODS: We surveyed English-language articles indexed in MEDLINE (1951-March 2017) and EMBASE (1974-March 2017). Articles were required to be prospective studies of a single over-the-counter cleanser or washing intervention in AV with an objective AV outcome measurement published in a peer-reviewed journal. RESULTS AND CONCLUSIONS: Fourteen prospective studies representing 671 participants were included in this review. Modalities investigated included face washing frequency, true soap/syndet cleansing bars, antiseptic cleansers, alpha and beta-hydroxy (i.e. salicylic) acid cleansers, and several proprietary formulations. Given the low number of well-performed clinical studies of cleansers and washing, it is difficult to formulate reliable recommendations. We hope that our findings highlight the necessity of further investigation in this area.

Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris.

When do efficacy outcomes in clinical trials correlate with clinical relevance? analysis of clindamycin phosphate 1.2%-benzoyl peroxide 3.75% gel in moderate to severe acne vulgaris.

Acne vulgaris (AV) is a common skin disease that is challenging to successfully treat due to its complex underlying pathophysiology and chronicity. Unrealistic expectations based on the desire for rapid and complete clearance or local tolerability reactions related to topical medications often lead to incomplete adherence with therapy, premature treatment cessation, and poor therapeutic outcomes. Despite stressing to patients the importance of compliance and the lag time of several weeks before visible improvement may be noted with treatments for AV, data on evaluation of the time taken to achieve a clinically meaningful improvement of AV that may be perceived by clinicians and patients are limited. Clindamycin phosphate 1.2%-benzoyl peroxide 3.75% (clindamycin-BP 3.75%) gel has been shown in pivotal trials to be effective and well tolerated in patients with moderate to severe AV. This article reviews a new concept referred to as time to onset of action (TOA), which is described in detail and illustrated using the pivotal trial data with clindamycin-BP 3.75% gel for treatment of AV.

In vitro evaluation of bioactive potential of Bacillus methylotrophicus YML008 against Propionibacterium acnes.

Acne vulgaris is the most common skin diseases that people experience during their lives. Thirteen rhizosphere isolates were screened against Propionibacterium acnes. The bacterium exhibited the highest activity against P. acnes was identified as Bacillus methylotrophicus YML008 by 16S rRNA gene sequencing. Scanning electron microscopy was used to assess the changes in morphology of P. acnes. Preliminary studies on the antimicrobial substance demonstrated the hydrophilic nature of compound with MIC of 0.17mg/ml and MBC of 0.3mg/ml. The cytotoxic effect of the extract was least (80% survival) as compared to benzyperoxide (40% survival). These results suggest YML008 as a promising bioresource and may be useful as a lead bacterium to develop a new type of anti-acne skin care prep to cure or prevent acne. Further, mechanism of action and proper clinical trials may be promising for this research.

[Bacterial resistance in acne? A meta-analysis of the controversy]. / ¿Resistencia en el acné? Un metaanálisis a propósito de la controversia.

BACKGROUND: Acne is one of the dermatological pathologies with the highest incidence around the world. It is a multifactorial disease and its treatment can be complex. Propionibacterium acnes play a key role in the inflammation of this dermatosis. Topical antibiotics, including mainly erythromycin and clindamycin, have been used, but there is controversy over their use due to the widely documented bacterial resistance. For this reason a meta-analysis of the publications over the past 10 years is presented in order to confirm this hypothesis. MATERIAL AND METHODS: A search was made of the publications over the past 10 years that included the results of antibiogams of patients with acne. MeSH type searches were performed with the terms "acne vulgaris", "Propionibacterium acnes", "topical administration", "treatment", "erythromycin", "clindamycin", "nadifloxacin", "antibacterial agent", "bacterial drug resistance" in PubMed, Ovid, EBSCO, Cochrane, ScienceDirect and ClinicalKey meta-searches. RESULTS: A total of 13 articles were found that met the inclusion criteria. The mean odds ratio (OR 1.24, 95% CI) of the articles showed a slight tendency toward resistance of Propionibacterium acnes. CONCLUSIONS: An increase in bacterial resistance to topical erythromycin and clindamycin can be confirmed, thus the use of these antibiotics is recommended in selective cases for short periods, and in combination with benzoyl peroxide for the best clinical outcome in patients with acne vulgaris.

In vitro antimicrobial activity of benzoyl peroxide against Propionibacterium acnes assessed by a novel susceptibility testing method.

Benzoyl peroxide (BPO), a therapeutic agent for acne vulgaris, was assessed for in vitro antimicrobial activity against Propionibacterium acnes using a novel broth microdilution testing that improved BPO solubility. We searched for a suitable culture medium to measure the minimum inhibitory concentration (MIC) of BPO against P. acnes and finally found the Gifu anaerobic medium (GAM) broth supplemented with 0.1(v/v)% glycerol and 2(v/v)% Tween 80, in which BPO dissolved up to 1250 µg/mL and P. acnes grew well. The MICs and minimum bactericidal concentrations (MBCs) of BPO against 44 clinical isolates of P. acnes collected from Japanese patients with acne vulgaris were determined by our testing method using the supplemented GAM broth. The MICs of BPO were 128 or 256 µg/mL against all isolates of P. acnes regardless of susceptibility to nadifloxacin or clindamycin. The MBCs of BPO were also 128 or 256 µg/mL against the same isolates. Moreover, BPO at the MIC showed a rapid bactericidal activity against P. acnes ATCC11827 in time-kill assay. In conclusion, we could develop a novel assay for the MIC and MBC determinations of BPO against P. acnes, which is reliable and reproducible as a broth microdilution testing and the present results suggest that BPO has a potent bactericidal activity against P. acnes.

Sensory and Functionality Differences of Whey Protein Isolate Bleached by Hydrogen or Benzoyl Peroxide.

UNLABELLED: Whey protein is a highly functional food ingredient used in a wide variety of applications. A large portion of fluid whey produced in the United States is derived from Cheddar cheese manufacture and contains annatto (norbixin), and therefore must be bleached. The objective of this study was to compare sensory and functionality differences between whey protein isolate (WPI) bleached by benzoyl peroxide (BP) or hydrogen peroxide (HP). HP and BP bleached WPI and unbleached controls were manufactured in triplicate. Descriptive sensory analysis and gas chromatography-mass spectrometry were conducted to determine flavor differences between treatments. Functionality differences were evaluated by measurement of foam stability, protein solubility, SDS-PAGE, and effect of NaCl concentration on gelation relative to an unbleached control. HP bleached WPI had higher concentrations of lipid oxidation and sulfur containing volatile compounds than both BP and unbleached WPI (P < 0.05). HP bleached WPI was characterized by high aroma intensity, cardboard, cabbage, and fatty flavors, while BP bleached WPI was differentiated by low bitter taste. Overrun and yield stress were not different among WPI (P < 0.05). Soluble protein loss at pH 4.6 of WPI decreased by bleaching with either hydrogen peroxide or benzoyl peroxide (P < 0.05), and the heat stability of WPI was also distinct among WPI (P < 0.05). SDS PAGE results suggested that bleaching of whey with either BP or HP resulted in protein degradation, which likely contributed to functionality differences. These results demonstrate that bleaching has flavor effects as well as effects on many of the functionality characteristics of whey proteins. PRACTICAL APPLICATIONS: Whey protein isolate (WPI) is often used for its functional properties, but the effect of oxidative bleaching chemicals on the functional properties of WPI is not known. This study identifies the effects of hydrogen peroxide and benzoyl peroxide on functional and flavor characteristics of WPI bleached by hydrogen and benzoyl peroxide and provides insights for the product applications which may benefit from bleaching.

Short communication: The influence of solids concentration and bleaching agent on bleaching efficacy and flavor of sweet whey powder.

Recent studies have demonstrated the effect of bleaching conditions and bleaching agent on flavor and functional properties of whey protein ingredients. Solids concentration at bleaching significantly affected bleaching efficacy and flavor effects of different bleaching agents. It is not known if these parameters influence quality of sweet whey powder (SWP). The purpose of this study was to determine the effects of solids concentration and bleaching agent on the flavor and bleaching efficacy of SWP. Colored cheddar whey was manufactured, fat separated, and pasteurized. Subsequently, the whey (6.7% solids) was bleached, concentrated using reverse osmosis (RO) to 14% solids, and then spray dried, or whey was concentrated before bleaching and then spray dried. Bleaching treatments included a control (no bleaching, 50 °C, 60 min), hydrogen peroxide (HP; 250 mg/kg, 50 °C, 60 min), benzoyl peroxide (50 mg/kg, 50 °C, 60 min), lactoperoxidase (20 mg/kg of HP, 50 °C, 30 min), and external peroxidase (MaxiBright, DSM Food Specialties, Delft, the Netherlands; 2 dairy bleaching units/mL, 50 °C, 30 min). The experiment was repeated in triplicate. Sensory properties and volatile compounds of SWP were evaluated by a trained panel and gas chromatography-mass spectrometry, respectively. Bleaching efficacy (norbixin destruction) and benzoic acid were measured by HPLC. Differences in bleaching efficacy, sensory and volatile compound profiles, and benzoic acid were observed with different bleaching agents, consistent with previous studies. Solids concentration affected bleaching efficacy of HP, but not other bleaching agents. The SWP from whey bleached with HP or lactoperoxidase following RO had increased cardboard and fatty flavors and higher concentrations of lipid oxidation compounds compared with SWP from whey bleached before RO. The SWP bleached with benzoyl peroxide after RO contained less benzoic acid than SWP from whey bleached before RO. These results indicate that solids concentration at bleaching and bleaching agent affect quality of SWP.

Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity.

A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes) which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide (BPO) (a potent antibacterial) was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of -43 mV; the entrapment efficiencies of tretinoin (TRA) and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 µg/cm(2) and 5.04±0.014 µg/cm(2), respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 µg, 2.68 µg, and 15.54 µg amounts of TRA and 68.85 µg, 59.98 µg, and 143.78 µg amounts of BPO were retained in the layers of skin, respectively. In vivo studies of the niosomal gel and antiacne cream of TRA and BPO showed that the niosomal gel was more efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower dose of BPO provided the same therapeutic index at targeted sites in comparison to the antiacne cream.

Development and characterization of a novel antiacne niosomal gel of rosmarinic acid.

The antibacterial and anti-inflammatory potential of rosemarinic acid (ROA), a naturally occurring ester of caffeic acid has been well reported. Antibacterial effect of ROA is attributed to nucleoid damage with an increase in spatial division and condensation of genetic material. ROA has been found dynamic against many human pathogenic bacterial strains but its inhibitory prospective has never been established against skin inflammations caused by Propionibacterium acne. The skin surface in acne prone areas is colonized with Staphylococcus aureus and Propionibacterium acnes which contribute to inflammation and acne. Resistance to current antimicrobial therapies suggested the need to explore new antimicrobial agents against acne. Present work included the preparation of ROA-loaded niosomes and their in vitro antimicrobial evaluation against P. acne and S. aureus. This work also included the development of niosomal gel of rosmarinic acid for sustained delivery to bacteria infected cells. Niosomes of rosmarinic acid were formulated by reverse phase evaporation method using different ratio of span 85 and cholesterol. The prepared formulations were evaluated for its vesicle size, entrapment efficiency, in vitro release study and antibacterial activity. In vivo study of developed formulation was conducted on Swiss albino mice in comparison with solution of plain drug and a marketed formulation of benzoyl peroxide. It was evident that niosomes are novel carrier for delivery of naturally occurring antimicrobial agents, in deeper tissues of skin. The results showed that drug-loaded niosomes dispersed in the gelling agent are an effective delivery system for treatment of acne vulgaris.

Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents.

Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

The role of benzoyl peroxide in the new treatment paradigm for acne.

Bacterial resistance became a true clinical concern for dermatologists in the 1980s, when the first reports emerged of the resistance of Propionibacterium acnes to oral antibiotics. Subsequent studies have documented acne treatment failure associated with resistance to topical antibiotics. Beyond dermatology practice, antibiotic resistance has now become recognized as a worldwide health concern. In contrast to antibiotics commonly used in the treatment of acne, benzoyl peroxide (BP)'s mechanism of action is different. Benzoyl peroxide is a bactericidal agent. Combining BP with a topical antibiotic in a stable formulation has been proven in clinical trials to reduce total P acnes count by 99.7% after 1 week of therapy, eliminating both susceptible and resistant strains of P acnes. However, we have recently noticed BP's benefits as monotherapy in the treatment of acne. Benzoyl peroxide works rapidly on P acnes without causing antibiotic resistance. Hence, we may have to reconsider the role of topical antibiotics such as clindamycin in the treatment paradigm of acne vulgaris.

Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1?

Acne pathogenesis has recently been linked to decreased nuclear FoxO1 levels and increased mTORC1 activity. This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1. Benzoyl peroxide (BPO), by activation of oxidative stress-inducible kinases, increases nuclear FoxO levels promoting Sestrin3-mediated AMPK activation. Furthermore, BPO-derived ROS may activate AMPK via ataxia-telangiectasia mutated. Isotretinoin and all-trans retinoic acid may stimulate FoxO gene expression. Doxycycline may enhance FoxOs nuclear retention by inhibiting the expression of exportin 1. Suppression of TNFα signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKß-TSC1-mediated mTORC1 activation. Erythromycin attenuates ERK1/2 activity and thereby increases TSC2. Azelaic acid may decrease mTORC1 by inhibiting mitochondrial respiration, increasing cellular ROS and nuclear FoxO levels. Antiandrogens may attenuate mTORC1 by suppressing mTORC2-mediated Akt/TSC2 signalling. This hypothesis unmasks a common mode of action of antiacne agents as either FoxO enhancers or mTORC1 inhibitors and thus provides a rational approach for the development of new antiacne agents.