The unseen use of antimicrobials: Drivers of human antibiotic use in a community in Thailand and implications for surveillance.

We investigated sociocultural and economic drivers of human antimicrobial use (AMU) in Thailand through ethnographic research, interviews, focus groups and a cross-sectional survey. This community-based study generated findings clustered around three key themes: treatment-seeking practices, medicine use, and interpretation of biomedical constructs. Participants sought care from public health facilities for chronic conditions, but medicines from the private sector were considered more powerful and were preferred for acute complaints. Many antibiotics were unrecognised as such by consumers due to the practice at private healthcare facilities of dispensing repackaged medicines without identifying labels. This unseen use of antibiotics is probably driven by economic drivers including market competition in the private sector, policy implementation drivers whereby rational drug use policies mainly target the public sector, behavioural drivers relating to treatment seeking-practices, and sociocultural drivers that influenced participants' understanding of medical terms and concepts. Participants regarded antibiotics as reducing inflammation and were uncertain about the distinctions between anti-inflammatories, antibiotics, and pain relievers. Antimicrobial Resistance (AMR) was understood as a form of drug tolerance to be remedied by changing the medicine. Community surveys may not provide accurate estimates of AMU where people are unable to distinguish antibiotics reliably from other medicines.

Antimicrobial Use in COVID-19 Patients in the First Phase of the SARS-CoV-2 Pandemic: A Scoping Review.

This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores the impact of documented antibiotic prescribing on treatment outcomes in COVID-19 patients. The review complies with PRISMA guidelines for Scoping Reviews and the protocol is registered with the Open Science Framework. In the first six months of the pandemic, there was a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs. 41.9% for patients with mild or moderate illness and those with severe or critical illness. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs. 13.1%), higher discharge rates (80.9% vs. 69.3%), and shorter length of hospital stay (9.3 days vs. 12.2 days). In the first 6 months of the pandemic, antibiotics were prescribed for COVID-19 patients regardless of severity of illness. A large proportion of antibiotic prescribing for mild and moderate COVID-19 patients did not have clinical evidence of a bacterial co-infection. Antibiotics may not be beneficial to COVID-19 patients without clinical evidence of a bacterial co-infection.

One Health drivers of antibacterial resistance: Quantifying the relative impacts of human, animal and environmental use and transmission.

OBJECTIVES: Antibacterial resistance (ABR) is a major global health security threat, with a disproportionate burden on lower-and middle-income countries (LMICs). It is not understood how 'One Health', where human health is co-dependent on animal health and the environment, might impact the burden of ABR in LMICs. Thailand's 2017 "National Strategic Plan on Antimicrobial Resistance" (NSP-AMR) aims to reduce AMR morbidity by 50% through 20% reductions in human and 30% in animal antibacterial use (ABU). There is a need to understand the implications of such a plan within a One Health perspective. METHODS: A model of ABU, gut colonisation with extended-spectrum beta-lactamase (ESBL)-producing bacteria and transmission was calibrated using estimates of the prevalence of ESBL-producing bacteria in Thailand. This model was used to project the reduction in human ABR over 20 years (2020-2040) for each One Health driver, including individual transmission rates between humans, animals and the environment, and to estimate the long-term impact of the NSP-AMR intervention. RESULTS: The model predicts that human ABU was the most important factor in reducing the colonisation of humans with resistant bacteria (maximum 65.7-99.7% reduction). The NSP-AMR is projected to reduce human colonisation by 6.0-18.8%, with more ambitious targets (30% reductions in human ABU) increasing this to 8.5-24.9%. CONCLUSIONS: Our model provides a simple framework to explain the mechanisms underpinning ABR, suggesting that future interventions targeting the simultaneous reduction of transmission and ABU would help to control ABR more effectively in Thailand.

Qualitative exploration of the experiences of men who use drugs of obtaining psychoactive medicinal products in Jordan.

In Jordan, almost any medication can be bought from pharmacies. This ready availability is linked with abuse. Previous literature describes medicine abuse from pharmacists' and general public perspectives. Here we investigate experiences of 17 men in addiction treatment in Amman (21-39 years) of obtaining psychoactive medicines. Alprazolam, clonazepam, bromazepam and tramadol were most commonly abused. Psychoactive medicines were obtained from street dealers, but pharmacies were preferred. Regulations appears ineffective; lack of understanding of pharmacists of the abuse potential of some medicines was perceived; 'softening rules' on supply was attributed to cultural and social norms around familiarity.

A qualitative exploration of the experiences of community dwelling older adults with sensory impairment/s receiving polypharmacy on their pharmaceutical care journey.

BACKGROUND: Most developed countries have increasing numbers of community dwelling older people with both multi-morbidity and sensory impairment that includes visual, hearing or dual impairment. Older people with sensory impairment are more likely to have chronic health conditions and to be in receipt of polypharmacy (>4 medicines). It is important to understand their experience of pharmaceutical care provision to facilitate a safe, appropriate and person centred approach. AIM: this study explored the pharmaceutical care experiences and perspectives of older people with sensory impairment receiving polypharmacy. DESIGN AND SETTING: exploratory qualitative study with semi-structured telephone or face-to-face interviews with community dwelling older adults with sensory impairment receiving polypharmacy in Scotland in 2016. METHODS: in total, 23 interviews were conducted with older people from seven of the 14 Scottish Health Board areas. SUBJECTS: over half the participants (n = 12) had dual sensory impairment, six had visual impairment and five had hearing impairment. RESULTS: three overarching themes were identified reflecting different stages of participants' pharmaceutical care journey: ordering and collection of prescriptions; medicine storage; and administration. At each stage of their journey, participants identified barriers and facilitators associated with their pharmaceutical care. CONCLUSIONS: this is the first comprehensive, in-depth exploration of the pharmaceutical care journey needs of older people with sensory impairment. As the number of community dwelling older people with sensory impairment and polypharmacy increases there is a requirement to identify challenges experienced by this population and offer solutions for safe and effective pharmaceutical care provision.

Quality indicators and community pharmacy services: a scoping review.

BACKGROUND: Quality indicators are a commonly used improvement tool in health care. There is growing interest and activity in the use of quality indicators to improve community pharmacy practice. OBJECTIVES: To conduct a scoping review of the use of quality indicators for community pharmacy practice, including their methods of development and evaluation. METHODS: Electronic databases (EMBASE and PubMed) were searched to identify papers published between January 2008 and April 2018. No limits were applied for language of publication or country of origin. Studies were included if they reported empirical data regarding the development or evaluation of quality indicators. All study designs were eligible for inclusion. Duplicate independent screening was undertaken of the search results. Data extraction was performed by one reviewer. RESULTS: Of the 988 records identified from the database search, 15 articles were included. The studies were conducted in 12 countries from six continents. Eleven studies described the development of quality indicators, eight of which included the evaluation of the psychometric properties of the indicators developed. Four studies examined the impact of quality indicators on practice all of which reported improvements in some aspects of quality, mainly with structure indicators rather than those relating to process and outcome. CONCLUSIONS: Whilst there is a growing emphasis on promoting improvement in community pharmacy services, evidence is lacking of the effect of indicators on improving quality. Measurable process and outcome indicators are needed. The future development of quality indicators would also benefit from a multi-stakeholder approach.

'Has she seen me?': a multiple methods study of the pharmaceutical care needs of older people with sensory impairment in Scotland.

OBJECTIVES: To explore the pharmaceutical care needs of, and service provision to, older people with sensory impairment (visual, hearing and dual impairment) on prescribed polypharmacy (≥4 medicines) in Scotland. DESIGN: Interviews were conducted with older people with sensory impairment and community pharmacy personnel, which informed the content of a subsequent national cross-sectional survey of community pharmacists. SETTING: Scotland, 2015-2016. PARTICIPANTS: Older people with sensory impairment and community pharmacy personnel. RESULTS: Interviews were completed with 23 older people with sensory impairment (dual impairment n=13, visual or hearing impairment n=5 of each) and 30 community pharmacy personnel from eight of 14 Scottish Health Boards. A total of 171 survey responses were received.Older people reported that they did not always disclose their sensory impairment to pharmacy personnel. They also reported that medicines were difficult to identify particularly when their name, shape or colour changed. Pharmacy personnel relied on visible cues such as white canes or guide dogs to identify visual impairment and suggested that hearing loss was less visible and more difficult to identify. Many assistive aids in support of medicine management, such as dosette boxes, seemed inadequate for complex medication regimens. Few community pharmacy personnel reported receiving training in the care of people with sensory impairment. CONCLUSIONS: This is the first comprehensive, multistakeholder, in-depth exploration of the pharmaceutical care needs of older people with sensory impairment. Strategies are needed to enable people with sensory impairment to disclose their impairment to pharmacy personnel (and other healthcare providers). Community pharmacy personnel require training to deliver person-centred pharmaceutical care for older people with sensory impairment particularly regarding communication with individuals in this vulnerable population.

Development of a filter to prevent infections with spore-forming bacteria in injecting drug users.

BACKGROUND: In heroin injectors, there have been a number of outbreaks caused by spore-forming bacteria, causing serious infections such as anthrax or botulism. These are, most likely, caused by injecting contaminated heroin, and our aim was to develop a filter that efficiently removes these bacteria and is also likely to be acceptable for use by people who inject drugs (i.e. quick, simple and not spoil the hit). METHODS: A prototype filter was designed and different filter membranes were tested to assess the volume of liquid retained, filtration time and efficiency of the filter at removing bacterial spores. Binding of active ingredients of heroin to different types of membrane filters was determined using a highly sensitive analytical chemistry technique. RESULTS: Heroin samples that were tested contained up to 580 bacteria per gramme, with the majority being Bacillus spp., which are spore-forming soil bacteria. To remove these bacteria, a prototype filter was designed to fit insulin-type syringes, which are commonly used by people who inject drugs (PWIDs). Efficient filtration of heroin samples was achieved by combining a prefilter to remove particles and a 0.22 µm filter to remove bacterial spores. The most suitable membrane was polyethersulfone (PES). This membrane had the shortest filtration time while efficiently removing bacterial spores. No or negligible amounts of active ingredients in heroin were retained by the PES membrane. CONCLUSIONS: This study successfully produced a prototype filter designed to filter bacterial spores from heroin samples. Scaled up production could produce an effective harm reduction tool, especially during outbreaks such as occurred in Europe in 2009/10 and 2012.

Electrospun Zein/PCL Fibrous Matrices Release Tetracycline in a Controlled Manner, Killing Staphylococcus aureus Both in Biofilms and Ex Vivo on Pig Skin, and are Compatible with Human Skin Cells.

PURPOSE: To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. METHODS: Zein/PCL triple layered fibrous dressings with entrapped tetracycline were electrospun. The successful entrapment of tetracycline in these dressings was validated. The successful release of bioactive tetracycline, the destruction of preformed biofilms, and the viability of fibroblast (FEK4) cells were investigated. RESULTS: The sustained release of tetracycline from these matrices led to the efficient destruction of preformed biofilms from Staphylococcus aureus MRSA252 in vitro, and of MRSA252 and ATCC 25923 bacteria in an ex vivo pig skin model using 1 × 1 cm square matrices containing tetracycline (30 µg). Human FEK4 cells grew normally in the presence of these matrices. CONCLUSIONS: The ability of the zein-based matrices to destroy bacteria within increasingly complex in vitro biofilm models was clearly established. An ex vivo pig skin assay showed that these matrices, with entrapped tetracycline, efficiently kill bacteria and this, combined with their compatibility with a human skin cell line suggest these matrices are well suited for applications in wound healing and infection control.

Killing bacteria within biofilms by sustained release of tetracycline from triple-layered electrospun micro/nanofibre matrices of polycaprolactone and poly(ethylene-co-vinyl acetate).

We report the controlled release of the antibiotic tetracycline (tet) HCl from a triple-layered electrospun matrix consisting of a central layer of poly(ethylene-co-vinyl acetate (PEVA) sandwiched between outer layers of poly-ε-caprolactone (PCL). These micro/nanofibre layers with tet successfully encapsulated (essentially quantitatively at 3 and 5 % w/w) in each layer, efficiently inhibited the growth of a panel of bacteria, including clinical isolates, as shown by a modified Kirby-Bauer disc assay. Furthermore, they demonstrated high biological activity in increasingly complex models of biofilm formation (models that are moving closer to the situation in a wound) by stopping biofilm formation, by killing preformed biofilms and killing mature, dense biofilm colonies of Staphylococcus aureus MRSA252. Tet is clinically useful with potential applications in wound healing and especially in complicated skin and skin-structure infections; electrospinning provides good encapsulation efficiency of tet within PCL/PEVA/PCL polymers in micro/nanofibre layers which display sustained antibiotic release in formulations that are anti-biofilm.

Zein/polycaprolactone electrospun matrices for localised controlled delivery of tetracycline.

We report the controlled release of the antibiotic tetracycline (Tet) from triple-layered (3L) electrospun matrices consisting of zein or a zein/PCL blend, where the drug was loaded into the central layer with the two outer layers acting as diffusion barriers. These fibrous matrices successfully encapsulated Tet and efficiently inhibited the growth of a clinical isolate, the methicillin-resistant Staphylococcus aureus strain MRSA252, as demonstrated in a modified Kirby-Bauer disc assay over 5 days. Whilst untreated zein fibres are unstable in an aqueous environment, rapidly shrinking due to plasticisation and film formation, blending zein with PCL stabilised the electrospun matrices and prevented them from shrinking. These 3L formulations display sustained antibiotic release and provide a proof of concept for zein-based polymeric matrices as wound dressings to treat or prevent bacterial infection. This is the first demonstration of the controlled release of a clinically used antibiotic from electrospun zein-based matrices.

Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate).

We report the controlled release of tetracycline (Tet) HCl from a three-layered electrospun matrix for the first time. Five formulations of electrospun poly-ε-caprolactone (PCL) and poly(ethylene-co-vinyl acetate) (PEVA) have been designed, prepared as micro/nanofibre layers, and assayed for the controlled release of the clinically useful antibiotic Tet HCl with potential applications in wound healing and especially in complicated skin and skin-structure infections. Tet HCl was also chosen as a model drug possessing a good ultraviolet (UV) chromophore and capable of fluorescence together with limited stability. Tet HCl was successfully incorporated (essentially quantitatively at 3 %, w/w) and provided controlled release from multilayered electrospun matrices. The Tet HCl release test was carried out by a total immersion method on 2 × 2 cm(2) electrospun fibrous mats in Tris or phosphate-buffered saline heated to 37 °C. The formulation PCL/PEVA/PCL with Tet HCl in each layer gave a large initial (burst) release followed by a sustained release. Adding a third layer to the two-layered formulations led to release being sustained from 6 days to more than 15 days. There was no detectable loss of Tet chemical stability (as shown by UV and NMR) or bioactivity (as shown by a modified Kirby-Bauer disc assay). Using Tet HCl-sensitive bacteria, Staphylococcus aureus (ATCC 25923), the Tet HCl-loaded three-layered matrix formulations were still showing significantly higher antibacterial effects on days 4 and 5 than commercially available Antimicrobial Susceptibility Test Discs of Tet HCl. Electrospinning provides good encapsulation efficiency of Tet HCl within PCL/PEVA/PCL polymers in micro/nanofibre layers which display sustained antibiotic release.