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1.
JAC Antimicrob Resist ; 6(1): dlae023, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38389802

ABSTRACT

Background: Antimicrobial resistance (AMR) is a global public health problem that is fuelled by the inappropriate prescribing of antibiotics, especially those from the 'watch' and 'reserve' antibiotic lists. The irrational prescribing of antibiotics is particularly prevalent in developing countries, including Zambia. Consequently, there is a need to better understand prescribing patterns across sectors in Zambia as a basis for future interventions. This study evaluated the prescribing patterns of antibiotics using the WHO prescribing indicators alongside the 'access, watch and reserve' (AWaRe) classification system post-COVID pandemic at a faith-based hospital in Zambia. Methods: A cross-sectional study was conducted from August 2023 to October 2023 involving the review of medical records at St. Francis' Mission Hospital in Zambia. A WHO-validated tool was used to evaluate antibiotic prescribing patterns alongside the AWaRe classification tool. Results: Out of 800 medical records reviewed, 2003 medicines were prescribed. Each patient received an average of 2.5 medicines per prescription. Antibiotics were prescribed in 72.3% of encounters, of which 28.4% were injectable. The most frequently prescribed antibiotics were amoxicillin (23.4%-access), metronidazole (17.1%-access), ciprofloxacin (8%-watch) and ceftriaxone (7.4%-watch), with 77.1% overall from the 'access' list. Encouragingly, 96.5% of the medicines were prescribed by their generic names and 98% were from the Zambia Essential Medicines List. Conclusions: There were high rates of antibiotic prescribing, including injectable antibiotics, which needs addressing going forward. It is crucial to implement targeted measures, including antimicrobial stewardship programmes, to improve future antibiotic prescribing in Zambia and reduce the risk of AMR.

2.
J Appl Microbiol ; 134(8)2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37480242

ABSTRACT

AIMS: This study aims to prioritize fungal strains recovered from under-explored habitats that produce new metabolites. HRMS dereplication is used to avoid structure redundancy, and molecular modelling is used to assign absolute configuration. METHODS AND RESULTS: MBC15-11F was isolated from an amphipod and identified using ITS, 28S, and ß-tubulin phylogeny as Aspergillus sydowii. Chemical profiling using taxonomic-based dereplication identified structurally diverse metabolites, including unreported ones. Large-scale fermentation led to the discovery of a new N-acyl adenosine derivative: (S)-sydosine (1) which was elucidated by NMR and HRESIMS analyses. Two known compounds were also identified as predicted by the initial dereplication process. Due to scarcity of 1, molecular modelling was used to assign its absolute configuration without hydrolysis, and is supported by advanced Mosher derivatization. When the isolated compounds were assessed against a panel of bacterial pathogens, only phenamide (3) showed anti-Staphylococcus aureus activity. CONCLUSION: Fermentation of A. sydowii yielded a new (S)-sydosine and known metabolites as predicted by HRESIMS-aided dereplication. Molecular modelling prediction of the absolute configuration of 1 agreed with advanced Mosher analysis.


Subject(s)
Amphipoda , Animals , Aspergillus , Staphylococcus aureus/genetics , Molecular Structure
3.
Beilstein J Org Chem ; 17: 2390-2398, 2021.
Article in English | MEDLINE | ID: mdl-34621401

ABSTRACT

Five new phenolic siderophores 1-5 were isolated from the organic extract of a culture broth in a modified SGG medium of Pseudomonas sp. UIAU-6B, obtained from sediments collected from the Oyun river in North Central Nigeria. The structure of the new compounds, pseudomonin A-C (1-3) and pseudomobactin A and B (4 and 5) isolated alongside two known compounds, pseudomonine (6) and salicylic acid (7), were elucidated based on high-resolution mass spectrometry, 1D and 2D NMR analyses. The absolute configuration of the threonine residue in compounds 1-5 was determined by Marfey analysis. The antimicrobial evaluation of compound 4 exhibited the most potent activity against vancomycin-sensitive Enterococcus faecium VS144754, followed by 3 and 5, with MIC values ranging from 8 to 32 µg/mL. Compounds 2 and 3 exhibited moderate activity against Mycobacterium tuberculosis H37Rv, with MIC values of 7.8 and 15.6 µg/mL, respectively. Plausible biosynthetic hypotheses toward the new compounds 1-5 were proposed.

4.
Molecules ; 26(14)2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34299519

ABSTRACT

There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.


Subject(s)
Curcumin/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacokinetics , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Biological Availability , Curcumin/pharmacokinetics , Curcumin/pharmacology , Delayed-Action Preparations/chemistry , Humans , Polyphenols/administration & dosage , Polyphenols/pharmacokinetics , Polyphenols/pharmacology
5.
J Pharm Pharmacol ; 73(11): 1427-1441, 2021 Oct 07.
Article in English | MEDLINE | ID: mdl-34132342

ABSTRACT

OBJECTIVES: Vesicular drug delivery has become a useful approach for therapeutic administration of pharmaceutical compounds. Lipid vesicles have found application in membrane biology, immunology, genetic engineering and theragnostics. This review summarizes topical delivery, specifically dermal/transdermal, ocular and transungual, via these vesicles, including future formulation perspectives. KEY FINDINGS: Liposomes and their subsequent derivatives, viz. niosomes, transferosomes, pharmacososmes and ethosomes, form a significant part of vesicular systems that have been successfully utilized in treating an array of topical disorders. These vesicles are thought to be a safe and effective mode of improving the delivery of lipophilic and hydrophilic drugs. SUMMARY: Several drug molecules are available for topical disorders. However, physicochemical properties and undesirable toxicity have limited their efficacy. Vesicular delivery systems have the potential to overcome these shortcomings due to properties such as high biocompatibility, simplicity of surface modification and suitability as controlled delivery vehicles. However, incorporating these systems into environmentally responsive dispersants such as hydrogels, ionic liquids and deep eutectic solvents may further enhance therapeutic prowess of these delivery systems. Consequently, improved vesicular drug delivery can be achieved by considering combining some of these formulation approaches.


Subject(s)
Administration, Ophthalmic , Drug Delivery Systems , Eye , Lipids/chemistry , Liposomes/chemistry , Nails , Skin , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical , Deep Eutectic Solvents/chemistry , Drug Carriers/chemistry , Humans , Skin Absorption
6.
Molecules ; 25(24)2020 Dec 16.
Article in English | MEDLINE | ID: mdl-33339110

ABSTRACT

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Biomimetics , COVID-19 Drug Treatment , Drug Delivery Systems/methods , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Host-Pathogen Interactions/drug effects , Humans , Nanostructures/chemistry , SARS-CoV-2/pathogenicity
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