ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model

by Ravi Jothi, Seong-Tshool Hong, Munkhtur Enkhtsatsral, Shunmugiah Karutha Pandian, Shanmugaraj Gowrishankar

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP’s therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 μg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 μg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

Exploring perceptions and operational considerations for use of a smartphone application to self-monitor blood pressure in pregnancy in Lombok, Indonesia: protocol for a qualitative study

Introduction

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal deaths globally and require close monitoring of blood pressure (BP) to mitigate potential adverse effects. Despite the recognised need for research on self-monitoring of blood pressure (SMBP) among pregnant populations, there are very few studies focused on low and middle income contexts, which carry the greatest burden of HDPs. The study aims to understand the perceptions, barriers, and operational considerations for using a smartphone software application to perform SMBP by pregnant women in Lombok, Indonesia.

Methods and analysis

This study includes a combination of focus group discussions, in-depth interviews and workshop observations. Pregnant women will also be provided with a research version of the smartphone BP application to use in their home and subsequently provide feedback on their experiences. The study will include pregnant women with current or past HDP, their partners and the healthcare workers involved in the provision of antenatal care services within the catchment area of six primary healthcare centres. Data obtained from the interviews and observations will undergo thematic analyses using a combination of both inductive and deductive approaches.

Ethics and dissemination

The study was approved by the World Health Organization (WHO) and Human Reproduction Programme (HRP) Research Project Review Panel and WHO Ethical Review Committee (A65932) as well as the Health Research Ethics Committee, Faculty of Medicine, Universitas Mataram in Indonesia (004/UN18/F7/ETIK/2023).

Findings will be disseminated through research publications and communicated to the Lombok district health offices. The analyses from this study will also inform the design of a subsequent impact evaluation.

Availability of access, watch, and reserve (AWaRe) group of antibiotics in community pharmacies located close to a tertiary care hospital in Lalitpur, Nepal

by Nisha Jha, Bibechan Thapa, Samyam Bickram Pathak, Sajala Kafle, Anish Mudvari, Pathiyil Ravi Shankar

Introduction

The access, watch, and reserve (AWaRe) classification of antibiotics was developed in 2019 by the WHO Expert Committee on the Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national, and global levels. The objectives of this study were to assess the availability of antibiotics as per WHO AWaRe classification at community pharmacies located around a tertiary care hospital in Lalitpur and to compare these antibiotics with the national essential medicine list of Nepal.

Method

The cross-sectional study was conducted at community pharmacies located within a two-kilometer radius of a teaching hospital from August to November 2022. A total of 82 community pharmacies registered with the Nepal Chemist and Druggists Association and the Department of Drug Administration were studied. Data was collected using a standard proforma containing the names of the antibiotics classified as per the WHO’s AWaRe classification.

Results

Access group of antibiotics, Ampicillin, (82;100%), Amoxycillin, (82;100%), Flucloxacillin, (82;100%), and Metronidazole, (82;100%) were available in all community pharmacies. Results from the watch group showed that Azithromycin, (80; 97.6%) was available in all pharmacies followed by Cefixime, (80; 97.6%), Ciprofloxacin, (73; 89%), Levofloxacin, (74; 90.2%)and Ofloxacin, (74; 90.2%). Linezolid, (24; 29.3%) was the most common antibiotics available from the reserve group of antibiotics. Colistin was the second commonly available antibiotic. The most available antibiotic from the not recommended group were Ampicillin/Cloxacillin (82; 100%), followed by Piperacillin/Sulbactam, (39; 47.6%). There were differences in the classification of antibiotics between the WHO AWaRe list and the Essential Medicines list of Nepal in terms of numbers of antibiotics listed.

Conclusion

Antibiotics from the not recommended and reserve groups were commonly available in community pharmacies. The implementation of antibiotic guidelines should be emphasized along with strict monitoring of the sale of antibiotics without a prescription in community pharmacy settings.