Five Percent Monolaurin Vaginal Gel for the Treatment of Bacterial Vaginosis: A Randomized Placebo-Controlled Trial.

OBJECTIVE: The aim of the study was to test the hypothesis that 5% monolaurin vaginal gel, a naturally occurring monoglyceride shown to have antimicrobial effects on vaginal pathogens without affecting Lactobacillus species, cures bacterial vaginosis (BV). MATERIALS AND METHODS: This was a multicenter, double-blinded, randomized controlled trial comparing 5% monolaurin vaginal gel to vehicle placebo (glycol-based) gel administered twice daily for 3 days. Nonpregnant, nonbreastfeeding women between ages 18 and 50 years were recruited and BV confirmed. Primary outcome was clinical cure assessed by resolution of all 4 Amsel criteria. Secondary outcomes included safety and tolerability assessed by solicited urogenital adverse events. Exploratory outcomes included colony counts for vaginal microbes associated with healthy vaginal flora (Lactobacillus species) and the dysbiosis often associated with BV (Gardnerella species and Mobiluncus species). A 2:1 test article to placebo randomization scheme was planned. RESULTS: One hundred nine women participated with 73 randomized to the treatment arm and 36 to the placebo arm. There was no significant difference in clinical cure for BV (p = .42) with 17% of the monolaurin group and 25% of the placebo group achieving clinical cure. Lactobacilli species counts increased in the monolaurin group compared with placebo (1.0 × 10 vs -5.2 × 10). Two thirds of both groups reported solicited urogenital adverse events, but these were mild to moderate with no significant difference between groups (p = .24). CONCLUSIONS: Monolaurin was no more clinically or microbiologically effective than placebo in curing BV. Future research should explore whether monolaurin may be used to increase Lactobacilli species.

Mono laurina na prevenção e tratamento de pacientes com COVID-19 / Mono laurine in the prevention and treatment of patients with Covid-19

OBJETIVO: Esta nota técnica tem por objetivo apresentar informações sobre o uso da monolaurina na prevenção e no tratamento de pacientes com COVID-19. DOS FATOS: Trata-se de despacho proveniente do Centro de Operações de Emergências em Saúde Pública (COE) e encaminhado ao Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE/MS). O despacho em questão apresenta um e-mail encaminhado pelo profissional Dr. Ronaldo Amaral de Paiva (vinculado à Universidade Federal de Viçosa), intitulado "Ações técnicas efetivas para o combate à Covid-19", que traz informações acerca do uso da monolaurina no tratamento da COVID-19 para análise no âmbito de suas competências e medidas julgadas pertinentes. BUSCA NA LITERATURA E SELEÇÃO DOS ESTUDOS: Com base na pergunta PICO estruturada, foram realizadas buscas nas bases de dados Medline (via PubMed) e Embase com acesso em 05 de maio de 2020. As estratégias de busca estão descritas conforme o Quadro 2 abaixo e mostram que não foram identificados estudos científicos sobre a questão de pesquisa. As plataformas de registros de ensaios clínicos ClinicalTrial.gov e International Clinical Trials Registry Platform (ICTRP), da Organização Mundial de Saúde (OMS), também foram consultadas. Foram utilizados os termos de busca: SARS-COV-2, COVID-19, 2019 novel coronavirus, 2019-nCoV, severe acute respiratory syndrome coronavirus 2, Wuhan coronavirus, COVID, monolaurin e glycerol monolaurate. Da mesma forma, nenhum estudo foi identificado em ambas as plataformas de registro. CONCLUSÕES: Embora haja evidências substanciais de ação antiviral de monoglicerídeos em vírus de RNA envelopados, não foram identificadas evidências científicas que corroborem o uso da monolaurina na prevenção ou tratamento de pacientes da COVID-19. Portanto, não foi possível aferir informações sobre um potencial efeito da substância sobre as membranas protetoras do SARS-CoV-2. Sendo assim, conclui-se que não há eficácia comprovada do uso na prevenção e tratamento da COVID-19. É prudente alertar sobre o crescente número de informações on-line, pretensamente fundadas em evidências científicas, que disseminam suposições de que produtos naturais, como o óleo de coco (23,24), teriam um efeito "protetor" contra a infecção pelo SARS-CoV-2. Não há qualquer regulamentação por nenhuma agência de vigilância sanitária nacional ou internacional para esses produtos que inclua essa finalidade de uso. Haja vista a precariedade de evidências acerca do tema, o presente documento será atualizado à medida que elas forem identificadas.

Staphylococcus aureus in Atopic Dermatitis: Past, Present, and Future.

: The role of Staphylococcus aureus (SA) in the pathogenesis and management in atopic dermatitis is rapidly evolving. The modern understanding of SA in atopic dermatitis now includes an expanded array of virulence factors, the interplay of clonal and temporal shifts in SA populations, and host factors such as filaggrin and natural moisturizing factor. New, emerging therapies that focus on long-term, targeted elimination of SA colonization are currently under investigation (Br J Dermatol 2017;17(1)63-71). Herein, we discuss and review the latest staphylococcal and microbiome-modifying therapies including topical antibiotics, topical natural oil fatty acids, anti-SA vaccines, microbial transplantation, vitamin D supplementation, dupilumab and proposed future investigative directions.

In Vivo Antifungal Activity of Monolaurin against Candida albicans Biofilms.

Monolaurin is a natural compound that has been known for its broad antimicrobial activities. We evaluate the antifungal activity of monolaurin against Candida albicans biofilms in vivo using a novel bioluminescent model to longitudinally monitor oral fungal infection. Oral fungal infection in vivo was performed using bioluminescent engineered C. albicans (SKCa23-ActgLUC) biofilms on Balb/c mice. The antifungal activity of monolaurin was determined by comparing three groups of mice (n=5/group): monolaurin, vehicle control, and positive control (nystatin). All mice were immunosuppressed with cortisone acetate and oral topical treatments were applied for 5 d. In vivo imaging system (IVIS) imaging was used to monitor the progression of infection over a 5-d period. Total photon flux and ex vivo microbiological analysis of the excised tongues were used to determine the overall fungal burden. Oral topical treatments of monolaurin have resulted in a significant decrease (p<0.05) in the total photon flux over 4 and 5 d post-infection in comparison to the vehicle control group. Furthermore, monolaurin treated group had a significant decrease in colony formation unit of tongue tissue compared to the vehicle control. Our findings support monolaurin as a promising antifungal compound in vivo, which may translate to its future use in the treatment of oral candidiasis.

Non-aqueous glycerol monolaurate gel exhibits antibacterial and anti-biofilm activity against Gram-positive and Gram-negative pathogens.

BACKGROUND: Skin and surgical infections due to Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii are causes of patient morbidity and increased healthcare costs. These organisms grow planktonically and as biofilms, and many strains exhibit antibiotic resistance. This study examines the antibacterial and anti-biofilm activity of glycerol monolaurate (GML), as solubilized in a non-aqueous vehicle (5% GML Gel), as a novel, broadly-active topical antimicrobial. The FDA has designated GML as generally recognized as safe for human use, and the compound is commonly used in the cosmetic and food industries. METHODS: In vitro, bacterial strains in broths and biofilms were exposed to GML Gel, and effects on bacterial colony-forming units (CFUs) were assessed. In vivo,subcutaneous incisions were made in New Zealand white rabbits; the incisions were closed with four sutures. Bacterial strains were painted onto the incision sites, and then GML Gel or placebo was liberally applied to cover the sites completely. Rabbits were allowed to awaken and were examined for CFUs as a function of exposure time. RESULTS: In vitro, GML Gel was bactericidal for all broth culture and biofilm organisms in <1 hour and <4 hour, respectively; no CFUs were detected after the entire 24 h test period. In vivo, GML Gel inhibited bacterial growth in the surgical incision sites, compared to no growth inhibition in controls. GML Gel significantly reduced inflammation, as viewed by lack of redness in and below the incision sites. CONCLUSIONS: Our findings suggest that 5% GML Gel is useful as a potent topical antibacterial and anti-inflammatory agent for prevention of infections.

Early events in sexual transmission of HIV and SIV and opportunities for interventions.

To constrain the growth of the HIV/AIDS pandemic and ultimately end it, effective measures must be developed to prevent sexual mucosal transmission, the major route by which new infections are acquired. I review sexual mucosal transmission of HIV and SIV, with a focus on vaginal transmission in the SIV rhesus macaque animal model, and the evidence for small founder populations of infected cells and the local expansion at the portal of entry necessary to establish systemic infection. These early events represent windows of maximum opportunity for interventions to prevent systemic infection. I highlight the paradoxical role the innate immune response plays in actually facilitating transmission, and a novel microbicide strategy that targets this innate response to prevent systemic infection, and I conclude with an agenda for future research that emphasizes mucosal immunology, virology and pathogenesis studies at each anatomic site of entry.

Glycerol monolaurate inhibits Candida and Gardnerella vaginalis in vitro and in vivo but not Lactobacillus.

We investigated the effects of glycerol monolaurate (GML) on Lactobacillus, Candida, and Gardnerella vaginalis human vaginal microflora. Our previous work demonstrated that 6 months of GML treatment vaginally does not alter lactobacillus counts in monkeys. Candida and G. vaginalis are commonly associated with vaginal infections in women, many becoming chronic or recurrent. In vitro growth inhibition studies determined the effects of GML (0 to 500 microg/ml) against multiple Candida species and G. vaginalis. A randomized, double-blind study investigated the effects of GML on vaginal microflora Lactobacillus, Candida, and G. vaginalis in colonized or infected women (n=36). Women self-administered intravaginal gels containing 0% (n=14), 0.5% (n=13), or 5% (n=9) GML every 12 h for 2 days. Vaginal swabs were collected before and immediately after the first gel administration and 12 h after the final gel administration. Swabs were tested for Lactobacillus, Candida, G. vaginalis, and GML. In vitro GML concentrations of 500 microg/ml were candicidal for all species tested, while a concentration of 10 microg/ml was bactericidal for G. vaginalis. Control and GML gels applied vaginally in women did not alter vaginal pH or Lactobacillus counts. Control gels reduced G. vaginalis counts but not Candida counts, whereas GML gels reduced both Candida and G. vaginalis. No adverse events were reported by participating women. GML is antimicrobial for Candida and G. vaginalis in vitro. Vaginal GML gels in women do not affect Lactobacillus negatively but significantly reduce Candida and G. vaginalis.

Inability of two topical treatments to influence the course of experimentally induced dermatophytosis in cats.

An experimental model of dermatophytosis was used to compare the efficacy of 2 topical antifungal treatments against Microsporum canis infection in cats. Infection was established in 24 cats by topical application of 10(5) M canis macroconidia to the skin of the lateral part of the abdomen under an occlusive bandage. Three groups of 6 cats each then were treated twice weekly for 18 weeks with chlorhexidine shampoo and dip, detergent shampoo vehicle only, or glyceryl monolaurate shampoo. Six cats were left untreated as controls. The experimentally induced infections strongly resembled naturally developing infections of moderate to severe nature. Signs of infection peaked in severity at 5 weeks after inoculation, then gradually resolved over 7 to 16 additional weeks. Dermatophytes were consistently isolated on culture for at least 8 weeks of treatment. Mycologic cure (defined as lack of dermatophyte isolation on 3 successive weekly cultures) was attained in 8 cats at the end of 18 weeks of treatment. Infections appeared to resolve at equivalent rates in all groups of cats, including controls. Consistent or meaningful significant differences in variables such as lesion size, clinical sign score, or total infection score were not found between treated and control groups. Our study revealed that this topical treatment regimen with chlorhexidine or glyceryl monolaurate is ineffective against M canis infection in cats.

Evaluation of postmilking teat germicides containing Lauricidin, saturated fatty acids, and lactic acid.

The efficacies of postmilking teat germicides containing Lauricidin (glyceryl monolaurate), saturated fatty acids, lactic acid, and lauric acid were determined against new IMI caused by Staphylococcus aureus and Streptococcus agalactiae in three controlled infection trials. In trial 1, a germicide was evaluated containing 1% Lauricidin, 5% caprylic and capric acids, 6% lactic acid, and .85% lauric acid. New IMI with Staph. aureus and Strep. agalactiae were reduced 81.3 and 49.6%, respectively. Trial 2 germicide involved an artificially aged sample of the formulation evaluated in trial 1. The germicide was aged at 40 degrees C for 5 mo, which was approximately equal to 2 yr at room temperature (24 degrees C). Reductions in new IMI were 81.2 and 27.5% for Staph. aureus and Strep. agalactiae, respectively. In trial 3, a teat germicide aged at ambient temperature for 33 mo, which was originally formulated to contain 1% Lauricidin, 5% caprylic and capric acids, and 6% lactic acid, was evaluated. Reductions in new IMI were 75.5 and 40.4% for Staph. aureus and Strep. agalactiae, respectively. The formulation evaluated in trial 1 was superior to other formulations in reducing new IMI by the two test organisms.

Influence of selected fatty acids upon plaque formation and caries in the rat.

Weanling rats were given high-sucrose cariogenic diets containing 2 per cent lauric acid, linoleic acid, nonanoic acid or monolaurin. Plaque accumulation was determined on the incisors of half the animals during only the last 3 days of the study and on the remaining animals at the conclusion of a 21-day test period when both sulcal and smooth-surface caries were assessed. No significant differences between the test groups in food consumption were observed nor were there any differences in body weight gain. The least amount of plaque was observed in the animals given monolaurin; the other fatty acids exerted no significant effect upon plaque accumulation. The smooth-surface caries data indicated that the least number of lesions occurred in the animals on the diet containing monolaurin. Nonanoic acid was significantly more effective in limiting sulcal caries than any of the other fatty acids studied. Thus both monolaurin and nonanoic acid have significant cariostatic activity in the rat.