Analogues of Disulfides from Allium stipitatum demonstrate potent anti-tubercular activities through drug efflux pump and Biofilm inhibition

Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB)

Public perceptions on the use of antibiotics at a market place in Kumasi, Ghana: A cross-sectional study

Background: Ghana launched its National Action Plan (NAP) to curb the spread of AMR in 2017. The current study was designed to gather data on the public perception concerning antibiotic use by surveying a population at Kejetia market in Kumasi with the aim of informing the design and implementation of public health campaigns linked to the NAP in Ghana. Method: A cross sectional study was conducted at the Kejetia market in Kumasi, Ghana between November 2017 and January 2018. Participants were adults over 18 years of age and data were gathered via a questionnaire regarding participants’ perceptions on the acquisition, use and disposal of antibiotics. Results: The number of participants was 302 of which nearly 60% were female. Statistically significant associations were identified between gender and level of education (p<0.05, Fisher’s exact test). Amoxicillin and metronidazole were the most commonly used antibiotics. Females were three times more likely to use these agents for diarrhoea than males and more likely to purchase them from non-pharmacy outlets and market pedlars. Conclusion: This study shows access to and the and misuse of antibiotics without prescriptions amongst this surveyed population. Antibiotics were also used more by females and by people with a lower level of education. This research highlights antibiotic misuse within a target population that needs addressing by implementation of the NAP

Development of a rapid, reliable and quantitative method – “SPOTi” for testing antifungal efficacy

A reference method for the antimicrobial susceptibility testing of common fungal pathogens such as dermatophytes, is currently lacking. In this study, we report the successful adaptation of solid agar-based spot culture growth inhibition assay (SPOTi) for dermatophytes, currently being used as a gold-standard in the anti-tubercular drug discovery field. The fungal-SPOTi assay correlated with the disc-diffusion method, and is validated using mycelial plugs. We propose the fungal-SPOTi as a high-throughput alternative to the disc-diffusion and broth micro-dilution anti-fungal assays to screen novel anti-fungals

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Natural Products as Antibiofilm Agents

Biofilms, are vastly structured surface-associated communities of microorganisms, enclosed within a self-produced extracellular matrix. Microorganisms, especially bacteria are able to form complex structures known as biofilms. The presence of biofilms especially in health care settings increases resistance to antimicrobial agents which poses a major health problem. This is because biofilm-associated persistent infections are difficult to treat due to the presence of multidrug-resistant microorganisms. This chapter will give an idea about documented agents including isolated compounds, crude extracts, decoctions, fractions, etc. obtained from natural sources such as plants, bacteria, fungi, sponge and algae with antibiofilm activities. Furthermore, we have done phylogenetic analysis to identify plant families most prolific in producing plant species and compounds with good antibiofilm properties so as to aid in prioritizing plant species to investigate in future studies. The data in this chapter will help serve as valuable information and guidance for future antimicrobial development

The Phytochemistry and Pharmacology of Tulbaghia, Allium, Crinum and Cyrtanthus: &lsquo;Talented&rsquo; Taxa from the Amaryllidaceae

Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer&rsquo;s disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional and pharmacological applications