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Research in Social & Administrative... Aug 2023Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This...
Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This should, improve antibiotic use, avoid inappropriate prescribing, reduce prescription numbers, aligning with national/international AMS targets. In primary care in the United Kingdom (UK) antibiotics are mainly prescribed for patients with urinary and respiratory symptoms (22.7% and 46% of all antibiotic prescriptions respectively). This study aimed to capture the time-series trends (2014-2022) for commonly prescribed antibiotics for respiratory and urinary tract infections in primary care in England. Trends for Amoxicillin, Amoxicillin sodium, Trimethoprim, Clarithromycin, Erythromycin, Erythromycin ethylsuccinate, Erythromycin stearate, Doxycycline hyclate, Doxycycline monohydrate and Phenoxymethylpenicillin (Penicillin V) were determined. In doing so providing evidence regarding meeting UK antibiotic prescribing rate objectives (a 15% reduction in human antibiotic use 2019-2024). Time series trend analysis of 62,949,272 antibiotic prescriptions from 6,370 General Practices in England extracted from the National Health Service (NHS) Business Services Authority web portal were explored. With additional investigation of prescribing rate trends by quintiles of the Index of Multiple Deprivation (IMD). Overall, there is a downwards trend in antibiotic prescribing for those explored. There is an association between IMD, geographical location, and higher antibiotic prescribing levels (prescribing hot spots). England has a well-documented North-South divide of health inequalities, this is reflected in antibiotic prescribing. The corona virus pandemic (COVID-19) impacted on AMS, with a rise in doxycycline and trimethoprim prescriptions notable in higher IMD areas. Since then, prescribing appears to have returned to pre-pandemic levels in all IMDs and continued to decline. AMS efforts are being adhered to in primary care in England. This study provides further evidence of the link between locality and poorer health outcomes (reflected in higher antibiotic prescribing). Further work is required to address antibiotic use in hot spot areas.
Topics: Humans; Anti-Bacterial Agents; State Medicine; COVID-19; Amoxicillin; Doxycycline; Inappropriate Prescribing; Penicillin V; Trimethoprim; Erythromycin; Primary Health Care; Practice Patterns, Physicians'
PubMed: 37183105
DOI: 10.1016/j.sapharm.2023.05.001 -
Analytical Chemistry Jul 2023Mass spectrometry-based large-scale multi-omics research has proven to be powerful in answering biological questions; nonetheless, it faces many challenges from sample...
Mass spectrometry-based large-scale multi-omics research has proven to be powerful in answering biological questions; nonetheless, it faces many challenges from sample preparation to downstream data integration. To efficiently extract biomolecules of different physicochemical properties, preparation of various sample type needs specific tailoring, especially of difficult ones, such as . In this study, we sought to develop a multi-omics sample preparation method starting with a single set of samples to save time, minimize variability, expand biomolecule coverage, and promote multi-omics integration. We investigated tissue disruption methods to effectively release biomolecules and optimized extraction strategies to achieve broader and more reproducible biomolecule coverage in proteomics, lipidomics, and metabolomics workflows. In our assessment, we also considered speediness and usability of the approaches. The developed method was validated through a study of 16 samples designed to shine light on mitochondrial unfolded protein response (UPRmt), induced by three unique stressors─knocking down electron transfer chain element , mitochondrial ribosome protein S5 , and antibiotic treatment Doxycycline. Our findings suggested that the method achieved great coverage of proteome, lipidome, and metabolome with high reproducibility and validated that all stressors triggered UPRmt in , although generating unique molecular signatures. Innate immune response was activated, and triglycerides were decreased under all three stressor conditions. Additionally, Doxycycline treatment elicited more distinct proteomic, lipidomic, and metabolomic response than the other two treatments. This method has been successfully used to process (data not shown) and can likely be applied to other organisms for multi-omics research.
Topics: Animals; Caenorhabditis elegans; Multiomics; Proteomics; Doxycycline; Reproducibility of Results; Mass Spectrometry; Metabolomics
PubMed: 37432911
DOI: 10.1021/acs.analchem.3c00734 -
Frontiers in Microbiology 2023Four randomized controlled trials have now established that doxycycline post exposure (sex) prophylaxis (PEP) can reduce the incidence of chlamydia and syphilis in men...
BACKGROUND
Four randomized controlled trials have now established that doxycycline post exposure (sex) prophylaxis (PEP) can reduce the incidence of chlamydia and syphilis in men who have sex with men. These studies have concluded that the risk of selecting for antimicrobial resistance is low. We evaluated this risk and using a infection model.
METHODS
We evaluated how long it took for doxycycline resistance to emerge during passage on doxycycline containing agar plates in 4 species - , , and . We then assessed if could acquire resistance to doxycycline (and cross resistance to other antimicrobials) during intermittent exposure to doxycycline in a model of doxycycline PEP.
RESULTS
In our passage experiments, we found that resistance first emerged in . By day 7 the MIC had increased from 2 mg/L to a median of 96 mg/L (IQR 64-96). Under various simulations of doxycycline PEP in the G. mellonella model, the doxycycline MIC of increased from 2 mg/L to 48 mg/L (IQR 48-84). Ceftriaxone and ciprofloxacin MICs increased over ten-fold. Whole genome sequencing revealed acquired mutations in ramR which regulates the expression of the AcrAB-TolC efflux pump.
CONCLUSION
Doxycycline PEP can select for doxycycline, ceftriaxone and ciprofloxacin resistance in in a G. mellonella model. The emergent ramR mutations were similar to those seen in circulating strains of . These findings suggest that we need to assess the effect of doxycycline PEP on resistance induction on a broader range of bacterial species than has hitherto been the case.
PubMed: 37711686
DOI: 10.3389/fmicb.2023.1208014 -
PloS One 2023Nutrition is sturdily and rapidly becoming the foremost determinant of health in today's Sars-Cov-2 and climate change ravaged world. While safe food sustains life,... (Review)
Review
Nutrition is sturdily and rapidly becoming the foremost determinant of health in today's Sars-Cov-2 and climate change ravaged world. While safe food sustains life, contamination obliterates its values and could result in death and short to long term morbidity. The purpose of this scoping review is to explore food contamination in Ghana, between 2001-2022. Using Arksey and O'Malley's procedure, a systematic literature search from PubMed, JSTOR, ScienceDirect, ProQuest, Scopus, Emeralds Insight, Google Scholar, and Google was carried out. Following the inclusion criteria, 40 published and grey literature were covered in this review. The review revealed the following: Studies on food contamination involving Greater Accra, Ashanti, Central, and Eastern Regions alone account for over 50% of the total number of such studies conducted in Ghana; regulators failed in enforcing regulations, monitoring and supervision; managers failed to provide adequate infrastructure and facilities. The most common food safety risks of public health concern are: i) micro-organisms (E. coli/faecal coliforms, Staphylococcus aureus, Salmonella spp, Bacillus cereus, and Viral hepatitis); ii) drugs (Amoxicillin, Chlortetracycline, Ciprofloxacin, Danofloxacin, and Doxycycline) and; iii) chemicals (Chlorpyrifos). Salad, vegetables, sliced mango, meat pie, and snail khebab are of high public health risks. The following deductions were made from the review: Highly contaminated food results in death, short to long term morbidity, economic loss, and threatens to displace Ghana's efforts at achieving the Sustainable Development Goals (SDG) 2. Thus, Government must resource key regulatory bodies to enhance their operational capacity, regulators must foster collaboration in monitoring and supervision of food vendors, and managers of food service outlets must provide adequate facilities to engender food safety culture.
Topics: Humans; Ghana; Public Health; Escherichia coli; COVID-19; SARS-CoV-2; Food Contamination
PubMed: 37561804
DOI: 10.1371/journal.pone.0288685 -
Revue Medicale Suisse Jan 2024The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe... (Meta-Analysis)
Meta-Analysis
The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe community-acquired pneumonia. Administration of doxycycline post-exposure prophylaxis reduced the risk of bacterial sexually transmitted infections at the risk of resistance selection. An herbal preparation decreased mortality in sepsis. A meta-analysis concludes that oseltamivir does not significantly reduce the risk of hospitalisation for influenza. Discontinuation of antibiotic prophylaxis during dental procedures in Sweden did not increase the incidence of viridans group Streptococcus endocarditis. Several studies have led to the introduction of RSV (Respiratory Syncytial Virus (RSV) vaccination. 2023 also saw the resurgence of invasive Group A Streptococcal infections, of which clinicians must be wary.
Topics: Humans; Communicable Diseases; Sepsis; Streptococcal Infections; Influenza, Human; Doxycycline
PubMed: 38231101
DOI: 10.53738/REVMED.2024.20.856-7.55 -
BMJ Open Dec 2023Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The...
Preconceptual administration of doxycycline in women with recurrent miscarriage and chronic endometritis: protocol for the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, a multicentre, double-blind, placebo-controlled, adaptive randomised trial with an embedded translational substudy.
INTRODUCTION
Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births.
METHODS AND ANALYSIS
Chronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as <5 CD138 positive cells per 10 mm) will also be followed up to test validity of the tool. The primary outcome is live births plus pregnancies ≥24 + 0 weeks gestation at the end of the trial, in the first or subsequent pregnancy. Secondary clinical outcomes will also be assessed. Exploratory outcomes will assess the effect of doxycycline treatment on the endometrial microbiota, the differentiation capacity of the endometrium and the senescent profile of the endometrium with CE.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the NHS Research Ethics Committee Northwest-Haydock (19/NW/0462). Written informed consent will be gained from all participants. The results will be published in an open-access peer-reviewed journal and reported in the National Institute for Health and Care Research journals library.
TRIAL REGISTRATION NUMBER
ISRCTN23947730.
Topics: Pregnancy; Female; Humans; Doxycycline; Endometritis; State Medicine; Abortion, Habitual; Chronic Disease; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38040426
DOI: 10.1136/bmjopen-2023-081470 -
Biomolecules Sep 2023Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune...
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed.
Topics: Humans; Matrix Metalloproteinase 2; Periodontal Ligament; Interleukin-17; Osteogenesis; Doxycycline; Periodontitis; Stem Cells; Cell Differentiation; Cells, Cultured
PubMed: 37892119
DOI: 10.3390/biom13101437 -
Journal of Translational Medicine Dec 2023Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health... (Review)
Review
Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.
Topics: Animals; Mice; Humans; Syphilis; Treponema pallidum; Anti-Bacterial Agents; Doxycycline; Vaccines
PubMed: 38105236
DOI: 10.1186/s12967-023-04685-4 -
Genes To Cells : Devoted To Molecular &... Feb 2024Mitophagy is programmed selective autophagy of mitochondria and is important for mitochondrial quality control and cellular homeostasis. Mitochondrial dysfunction and...
Mitophagy is programmed selective autophagy of mitochondria and is important for mitochondrial quality control and cellular homeostasis. Mitochondrial dysfunction and impaired mitophagy are closely associated with various diseases, including heart failure and diabetes. To better understand the pathophysiological role of mitophagy, we generated doxycycline-inducible mitophagy mice using a synthetic mitophagy adaptor protein consisting of an outer mitochondrial membrane targeting sequence and an engineered LIR. To evaluate the activation of mitophagy upon doxycycline treatment, we also generated mitophagy reporter mito-QC mice in which mitochondria tandemly express mCherry and GFP, and only GFP signals are lost in acidic lysosomes subjected to mitophagy. With the ROSA26 promoter-driven rtTA, mitophagy was observed at least in heart, liver, and skeletal muscle. We investigated the relationship between mitophagy activation and pressure overload heart failure or high fat diet-induced obesity. Unexpectedly, we were unable to confirm the protective effect of mitophagy in these two pathological models. Further titration of the level of mitophagy induction is required to demonstrate the potency of the protective effects of mitophagy in disease models.
Topics: Mice; Animals; Mitophagy; Doxycycline; Mitochondria; Mitochondrial Membranes; Heart Failure; Autophagy
PubMed: 38131500
DOI: 10.1111/gtc.13091 -
The Lancet. Infectious Diseases Nov 2023Syphilis is a bacterial infection caused by Treponema pallidum and is primarily transmitted via skin-to-skin or mucosal contact during sexual encounters, or through... (Review)
Review
Syphilis is a bacterial infection caused by Treponema pallidum and is primarily transmitted via skin-to-skin or mucosal contact during sexual encounters, or through vertical transmission during pregnancy. Cases continue to rise globally across various demographic groups despite effective treatment and prevention interventions. We discuss the case of a 28-year-old cisgender man who presented with secondary syphilis 1 month after being inadequately treated for primary syphilis. Individuals can present with symptoms and signs of syphilis to clinicians of various subspecialties due to diverse clinical presentation. All health-care providers should be able to identify the common and less common manifestations of this infection, and adequate treatment and follow-up are crucial to preventing serious sequelae. Novel biomedical prevention interventions, such as doxycycline post-exposure prophylaxis, are on the horizon.
Topics: Male; Pregnancy; Female; Humans; Adult; Syphilis; Treponema pallidum; Doxycycline; Treatment Outcome
PubMed: 37414065
DOI: 10.1016/S1473-3099(23)00211-6