Reduction Of Antimicrobial Resistance Research Articles

Natural products from food sources can alter the spread of antimicrobial resistance plasmids in Enterobacterales.

Antimicrobial resistance (AMR) poses a significant threat to global public health. Notably, resistance to carbapenem and extended-spectrum β-lactam antibiotics in Gram-negative bacteria is a major impediment to treating infections. Genes responsible for antibiotic resistance are frequently carried on plasmids, which can transfer between bacteria. Therefore, exploring strategies to prevent this transfer and the prevalence of AMR plasmids is timely and pertinent. Here, we show that certain natural product extracts and associated pure compounds can reduce the conjugation of AMR plasmids into new bacterial hosts. Using our established high-throughput fluorescence-based flow cytometry assay, we found that the natural products were more active in reducing transmission of the IncK extended-spectrum β-lactamase-encoding plasmid pCT in Escherichia coli EC958c, compared to Klebsiella pneumoniae Ecl8 carrying the IncFII carbapenemase-encoding plasmid pKpQIL. The exception was the natural product rottlerin, also active in K. pneumoniae. In classical conjugation assays, rottlerin also reduced the conjugation frequency of the IncFII bla NDM-1 carrying plasmid pCPE16_3 from a clinical K. pneumoniae isolate. Our data indicate that the natural products tested here, in their current molecular structure, reduced conjugation by a small amount, which is unlikely to achieve a large-scale reduction in AMR in bacterial populations. However, certain natural products like rottlerin could provide a foundation for further research into compounds with effective anti-plasmid activity.

Epidemiology and Impact of Anti-Pneumococcal Vaccination and COVID-19 on Resistance of Streptococcus pneumoniae Causing Invasive Disease in Piedmont, Italy.

The international surveillance of antimicrobial resistance (AMR) reports S. pneumoniae as one of leading causes of death associated with AMR. Against invasive disease, several vaccinations are available and a reduction in AMR in S. pneumoniae has been observed. Here, we evaluated the impact of anti-pneumococcal vaccination policy and the SARS-CoV2 outbreak on AMR in S. pneumoniae causing invasive disease. We collected all strains of S. pneumoniae causing invasive disease from 2008 in the Piedmont region (Italy). Each strain was typed in order to identify the serogroup and data about AMR were collected. The population under surveillance was classified as infants, children, adults, and the old population. We collected n = 2076 S. pneumoniae strains, with 21.9% and 40.3% being resistant to penicillin G and erythromycin, respectively. We reported an increased risk of infection with penicillin-resistant S. pneumoniae among all populations and evaluated whether the infection was caused by a serotype included in the vaccine formulation. A similar increase was observed after the SARS-CoV2 outbreak. In the Piedmont region, subsequently to the introduction of anti-pneumococcal vaccination, a significant increase in the risk of penicillin G-resistant invasive pneumococcal disease among infants and old population was reported. No significant impact was found for the SARS-CoV2 outbreak.

Reduction in antimicrobial resistance in a watershed after closure of livestock farms

Natural environments play a crucial role in transmission of antimicrobial resistance (AMR). Development of methods to manage antibiotic resistance genes (ARGs) in natural environments are usually limited to the laboratory or field scale, partially due to the complex dynamics of transmission between different environmental compartments. Here, we conducted a nine-year longitudinal profiling of ARGs at a watershed scale, and provide evidence that restrictions on livestock farms near water bodies significantly reduced riverine ARG abundance. Substantial reductions were revealed in the relative abundance of genes conferring resistance to aminoglycosides (42%), MLSB (36%), multidrug (55%), tetracyclines (53%), and other gene categories (59%). Additionally, improvements in water quality were observed, with distinct changes in concentrations of dissolved reactive phosphorus, ammonium, nitrite, pH, and dissolved oxygen. Antibiotic residues and other pharmaceuticals and personal care products (PPCPs) maintain at a similarly low level. Microbial source tracking demonstrates a significant decrease in swine fecal indicators, while human fecal pollution remains unchanged. These results suggest that the reduction in ARGs was due to a substantial reduction in input of antibiotic resistant bacteria and genes from animal excreta. Our findings highlight the watershed as a living laboratory for understanding the dynamics of AMR, and for evaluating the efficacy of environmental regulations, with implications for reducing environmental risks associated with AMR on a global scale.

The Antimicrobial Effect of Cornus mas L. and Sorbus aucuparia L. Fruit Extracts against Resistant Uropathogens in Correlation with the Prevalence of Urinary Tract Infections in Companion Animals.

Urinary tract infections (UTIs) are a widespread condition in pets, with many antibiotics being prescribed, contributing to the rise in antimicrobial resistance, which is a worldwide threat. This study's main objective was to analyze the in vitro antimicrobial activity of Cornus mas and Sorbus aucuparia fruit hydro-ethanolic extracts towards bacteria identified in the urine of companion animals experiencing UTIs. Urine samples were collected from dogs and cats (n = 83; 47 negative, 36 positive); several bacterial strains were identified (n = 49) belonging to the Escherichia, Enterococcus, Staphylococcus, Proteus, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter, Leclercia, and Kocuria genera. Bacterial susceptibility was tested using the disk diffusion method, with the majority being resistant to several beta-lactams, quinolones, trimethoprim/sulfamethoxazole, and nitrofurantoin. Subsequently, 13 resistant isolates were selected to evaluate the fruits extracts' antimicrobial potential using the agar well diffusion and broth microdilution methods. Cornus mas exhibited the greatest activity against Gram-negatives (primarily Pseudomonas luteola), while Sorbus aucuparia showed maximum effects towards Gram-positives (particularly Enterococcus faecalis). The MIC was 0.01 μg/μL for both extracts; the MBC was 0.08 μg/μL for Cornus mas and 0.05 μg/μL for Sorbus aucuparia. However, Cornus mas showed a stronger bactericidal effect. This is the first study to investigate these fruit extracts in UTI isolates of companion animals, and these extracts might be used as substitutes or adjuvants for antibiotics, thus contributing to a reduction in antimicrobial resistance.

Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1

The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants. In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 μg/mL and 4 μg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives. We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 μg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433(99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 μg/mL and 4 μg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data. Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants. National Natural Science Foundation of China, and National Key Research and Development Program of China.

Phenotypic and genotypic characterization of antimicrobial resistances reveals the effect of the production chain in reducing resistant lactic acid bacteria in an artisanal raw ewe milk PDO cheese

Antimicrobial resistance (AMR) is a significant public health threat, with the food production chain, and, specifically, fermented products, as a potential vehicle for dissemination. However, information about dairy products, especially raw ewe milk cheeses, is limited. The present study analysed, for the first time, the occurrence of AMRs related to lactic acid bacteria (LAB) along a raw ewe milk cheese production chain for the most common antimicrobial agents used on farms (dihydrostreptomycin, benzylpenicillin, amoxicillin and polymyxin B). More than 200 LAB isolates were obtained and identified by Sanger sequencing (V1-V3 16S rRNA regions); these isolates included 8 LAB genera and 21 species. Significant differences in LAB composition were observed throughout the production chain (P ≤ 0.001), with Enterococcus (e.g., E. hirae and E. faecalis) and Bacillus (e.g., B. thuringiensis and B. cereus) predominating in ovine faeces and raw ewe milk, respectively, along with Lactococcus (L. lactis) in whey and fresh cheeses, while Lactobacillus and Lacticaseibacillus species (e.g., Lactobacillus sp. and L. paracasei) prevailed in ripened cheeses. Phenotypically, by broth microdilution, Lactococcus, Enterococcus and Bacillus species presented the greatest resistance rates (on average, 78.2 %, 56.8 % and 53.4 %, respectively), specifically against polymyxin B, and were more susceptible to dihydrostreptomycin. Conversely, Lacticaseibacillus and Lactobacillus were more susceptible to all antimicrobials tested (31.4 % and 39.1 %, respectively). Thus, resistance patterns and multidrug resistance were reduced along the production chain (P ≤ 0.05). Genotypically, through HT-qPCR, 31 antimicrobial resistance genes (ARGs) and 6 mobile genetic elements (MGEs) were detected, predominating Str, StrB and aadA-01, related to aminoglycoside resistance, and the transposons tnpA-02 and tnpA-01. In general, a significant reduction in ARGs and MGEs abundances was also observed throughout the production chain (P ≤ 0.001). The current findings indicate that LAB dynamics throughout the raw ewe milk cheese production chain facilitated a reduction in AMRs, which has not been reported to date.

Reduction of antimicrobial resistance: Advancements in nature-based wastewater treatment

Water scarcity, affecting one-fifth of the global population, is exacerbated by industrial, agricultural, and population growth pressures on water resources. Wastewater, containing Contaminants of Emerging Concern (CECs) such as antibiotics, presents environmental and health hazards. This study explores a Nature-Based Solution (NBS) using Constructed Wetlands (CWs) for wastewater reclamation and CECs removal. Two CW configurations (Vertical-VCW and Hybrid-HCW) were tested for their efficacy. Results show significant reduction in for all the chemico-physical and biological parameters meeting Italian water reuse standards. Furthermore, Antibiotic Resistant Bacteria (ARB) and Antibiotic Resistant Genes (ARGs) were effectively reduced, emphasizing the potential of the CWs in mitigating Antimicrobial Resistance (AMR). Lettuce seedlings irrigated with the treated wastewater exhibited no ARB/ARGs transfer, indicating the safety of the reclaimed wastewater for agricultural use. Overall, CWs emerge as sustainable Nature Based Solutions (NBS) for wastewater treatment, contributing to global water conservation efforts amid escalating water scarcity challenges.

Review: Current challenges in poultry nutrition, health, and welfare.

The poultry industry has benefited greatly from advances in genetics, nutrition, housing and management strategies. Geneticists have made welfare and health traits important components of selection programs, and in general, modern, high-producing poultry are healthier than 30years ago. However, increased productivity means that the birds are closer to their physiological limits, and nutrition, environment and management have become increasingly important. The move away from in-feed antibiotic growth promotors has resulted in challenges in maintaining gut health and consequently, bird performance. However, as the industry adapts to production without the use of antibiotic growth promotors, long-term benefits may be realized due to a reduction in antimicrobial resistance. Intensive selection for meat yield and efficiency are associated with an increased risk of muscle myopathies that affect bird health and meat quality. As genetic selection increased broiler production traits, it became necessary to restrict parent stock nutrient intake in order to prevent excessive muscle and fat deposition, reduce metabolic disease, and maintain ovarian control. With continued selection for broiler production traits, the degree of restriction implemented has become a welfare issue. Additionally, recent research suggests that highly efficient broiler lines may have limited fat deposition and therefore energy reserves to support sexual maturation and egg production, especially if typical broiler breeder BW targets are maintained. A re-examination of broiler breeder feeding programs is necessary to maintain productivity and welfare. Modern laying hens are capable of laying cycles in excess of 100weeks of age. This has reduced the use of stress-inducing forced molting programs and reduces the total number of hens needed to meet the demand for egg production. The important role of the skeletal system in eggshell deposition demands that skeletal development during rearing be carefully managed to avoid shell and skeletal problems at the end of the production cycle. As the production potential of modern poultry continues to increase through genetic and genomic selection, even greater care must be paid in order to maintain bird health and welfare. The poultry industry has successfully faced many challenges in the past and is likely to overcome the existing challenges as well.

Probiotics beyond the farm: Benefits, costs, and considerations of using antibiotic alternatives in livestock

The increasing global expansion of antimicrobial resistant infections warrants the development of effective antibiotic alternative therapies, particularly for use in livestock production, an agricultural sector that is perceived to disproportionately contribute to the antimicrobial resistance (AMR) crisis by consuming nearly two-thirds of the global antibiotic supply. Probiotics and probiotic derived compounds are promising alternative therapies, and their successful use in disease prevention, treatment, and animal performance commands attention. However, insufficient or outdated probiotic screening techniques may unintentionally contribute to this crisis, and few longitudinal studies have been conducted to determine what role probiotics play in AMR dissemination in animal hosts and the surrounding environment. In this review, we briefly summarize the current literature regarding the efficacy, feasibility, and limitations of probiotics, including an evaluation of their impact on the animal microbiome and resistome and their potential to influence AMR in the environment. Probiotic application for livestock is often touted as an ideal alternative therapy that might reduce the need for antibiotic use in agriculture and the negative downstream impacts. However, as detailed in this review, limited research has been conducted linking probiotic usage with reductions in AMR in agricultural or natural environments. Additionally, we discuss the methods, including limitations, of current probiotic screening techniques across the globe, highlighting approaches aimed at reducing antibiotic usage and ensuring safe and effective probiotic mediated health outcomes. Based on this information, we propose economic and logistical considerations for bringing probiotic therapies to market including regulatory roadblocks, future innovations, and the significant gaps in knowledge requiring additional research to ensure probiotics are suitable long-term options for livestock producers as an antibiotic alternative therapy.

Rapid Molecular Point of Care Testing for Detection of Influenza A, B Viruses and Respiratory Syncytial Virus Versus Multiplex PCR

Introduction: Rapid detection of influenza viruses and respiratory syncytial virus (RSV) can be achieved by having rapid molecular point of care tests (POCTs). This expedites the diagnosis attributed by having similar clinical presentations leading to facilitation of precision medicine and reduction of antimicrobial resistance. The growing number of POCTs foster the need to ensure that these POCTs have satisfactory and reliable performance. With that the aim of this study is to evaluate the performance of rapid molecular POCT regarded as ‘X’ for the detection of Influenza viruses and RSV in comparison to multiplex PCR. Methods: A laboratory-based study was conducted from January to December 2020 which involved analysis of 116 nasopharyngeal swabs, tested using POCT X and multiplex PCR as a method of reference. The performance analysis incorporated the sensitivity, specificity, positive and negative predicted values determination. The cycle threshold values were reviewed for discordant results. Results: The POCT X demonstrated sensitivity of 88.57% with 100% specificity for Influenza A virus, and 85.71% of sensitivity with 100% specificity for influenza B virus detection. Meanwhile it revealed 100% sensitivity and specificity for RSV detection. There were ten specimens demonstrating discordant results whereby viruses were not detected by POCT X, however detected by multiplex PCR. The POCT X was not able to detect eight (12.9%) and two (16.7%) influenza A and B viruses respectively. Conclusion: The overall performance of POCT X was corresponded to multiplex PCR. This best served as a steadfast ancillary test for influenza and RSV infection.

Current Insights Regarding the Role of Farm Animals in the Spread of Antimicrobial Resistance from a One Health Perspective.

Simple SummaryAntimicrobial resistance is of critical concern for both human and veterinary medicine worldwide. Many bacterial infections are currently very difficult to treat due to the presence of several mechanisms involved in bacterial resistance to marketed antimicrobials. Preserving the effectiveness of currently available antimicrobials and reducing the burden of infections caused by resistant bacteria is a priority for competent authorities operating in both sectors. It has been perceived that the livestock sector is a primary contributor to the spread of bacterial resistance in both humans and the environment. This review examined the recent scientific literature on this topic in order to explore the relationship between antimicrobials use in farm animals and the selection of bacterial resistance in this sector and its subsequent dissemination to humans. Recent data indicated that the global biomass-adjusted amount of antimicrobials consumed by farm animals was slightly higher than the amounts used in humans, while the reel contribution of farm animals in the spread of AMR to humans is probably very low compared to initial estimations. However, this review highlights the importance of the close collaboration between veterinary and human medicine, as part of the ‘One Health’ approach, to preserve the longevity of antimicrobials.Antimicrobial resistance (AMR) represents a global threat to both human and animal health and has received increasing attention over the years from different stakeholders. Certain AMR bacteria circulate between humans, animals, and the environment, while AMR genes can be found in all ecosystems. The aim of the present review was to provide an overview of antimicrobial use in food-producing animals and to document the current status of the role of farm animals in the spread of AMR to humans. The available body of scientific evidence supported the notion that restricted use of antimicrobials in farm animals was effective in reducing AMR in livestock and, in some cases, in humans. However, most recent studies have reported that livestock have little contribution to the acquisition of AMR bacteria and/or AMR genes by humans. Overall, strategies applied on farms that target the reduction of all antimicrobials are recommended, as these are apparently associated with notable reduction in AMR (avoiding co-resistance between antimicrobials). The interconnection between human and animal health as well as the environment requires the acceleration of the implementation of the ‘One Health’ approach to effectively fight AMR while preserving the effectiveness of antimicrobials.

Rational Use of Antibiotics: An Area of Concern

Published on:June 2022Journal of Young Pharmacists, 2022; 14(2):165-168Review Article | doi:10.5530/jyp.2022.14.31 Authors: Sougata Sarkar,1 Vartika Srivastava,2,*Shambo Samrat Samajhdar,1 Chaitali Pattanayak,2 Santanu Tripathi3 1Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, INDIA. 2Department of Pharmacology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha INDIA.3Department of Pharmacology, Netaji Subhas Medical College and Hospital, Patna, Bihar, INDIA. Abstract: Most of the IPD (Inpatient department) and OPD (Outpatient department) patients receive a course of antibiotics either for treatment or prevention of infection or during discharge. The therapeutic outcome with an antibiotic depends mostly on choice of appropriate agent. The selection of antibiotic depends on causative agent, patient factors, clinical pharmacology of antibiotics and its cost effectiveness. Antimicrobial resistance (AMR) occurs when microbes like bacteria, parasites, viruses and fungi become resistant to antimicrobial drugs that are used for treatment of various diseases leading to decreased effectiveness, difficulty in treatment of disease and hence requiring multiple therapeutic options. Antimicrobial stewardship is a coordinated intervention, designed to improve and measure the appropriate use of antimicrobial agents, by promoting the selection of optimal antimicrobial drug regimen including dosing, duration of therapy and route of administration. To strengthen the implementation of rational antibiotic use and reduction of antimicrobial resistance, WHO (World Health Organisation) in 2019 introduced “AWaRe” classification of antibiotics that includes details of 180 antibiotics classified as Access, Watch or Reserve, their pharmacological classes, Anatomical Therapeutic Chemical (ATC) codes and WHO Essential Medicines List status. One health approach is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and environment. Recently, WHO issued new guidelines regarding the use of antimicrobials in animals producing food, recommending the restricted use of such medicines in growth promotion or prevention of disease in healthy animals. Hence rational use of antibiotics is important for successful treatment outcome and prevention of emerging drug resistance for broader community.Key words: Antibiotics, Antibiotic resistance, Antibiotic stewardship, AWaRe Classification, One health approach.

Phenotypic antimicrobial resistance (AMR) of avian pathogenic Escherichia coli (APEC) from broiler breeder flocks between 2009 and 2018

Colibacillosis is one of the most important diseases in poultry production. The use of antimicrobials remains a therapeutic cornerstone for avian pathogenic E. coli (APEC), thereby contributing to the development of antimicrobial resistance (AMR). The aim of this study was to characterize AMR in broiler breeder flocks reared under commercial conditions. Data covering ten years, from 2009 to 2018, were used to evaluate the phenotypic AMR of 264 APEC obtained from 158 broiler breeder flocks of a large company in Portugal. The APEC isolates were tested against eleven antimicrobials by the Kirby-Bauer disk diffusion test. The annual proportion of AMR was calculated by dividing the number of APEC with phenotypic resistance by the total number of APEC isolated that year. Similarly, the overall AMR of the whole period was calculated. The relationship of antimicrobial resistance with time (years) was investigated with a generalized linear model using logistic regression. The overall AMR of the 10-year period was: amoxicillin 78%, ampicillin 73.5%, tetracycline 63.3%, doxycycline 56.4%, apramycin 34.5%, neomycin 68.2%, enrofloxacine 32.6%, flumequine 39.4%, co-trimoxazole 47.7%, florfenicol 46.6% and lincospectin 66.3%. Over time, a significant decrease in AMR was observed for amoxicillin and ampicillin, neomycin, flumequine, co-trimoxazole, florfenicol and lincospectin. Multidrug resistance (MDR) decreased from 100% in 2009 to 48% in 2018. Only 7 (2.7%) APEC strains were fully susceptible to all tested antimicrobials. The decrease over time of AMR in APEC likely reflects the efficacy of manifold improvements in broiler breeder production systems. A further reduction in AMR is still desirable.

The Implications of Vaccines in Older Populations.

Mean longevity is increasing worldwide, with major consequences for public health worldwide, as the global population of adults aged over 65 years now exceeds the number of children under 5 for the first time in history. The ageing process over the life course is extremely heterogeneous, and it will be important to promote and enhance healthy ageing worldwide. Vaccination is a key player in the healthy ageing process, both at the individual and the community level. We review here the contribution of vaccines to individual and community health. At an individual level, we highlight the prevention of infectious diseases, as well as other, less well-known benefits of vaccination, such as modulation of the inflammatory process. We then underline the importance of vaccination in achieving herd immunity and reducing the transmission of pathogens in the community. Finally, at a community level, another important benefit of vaccination is the reduction in antimicrobial resistance. Taken together, these effects contribute to ensuring the best health, for the greatest number, for the longest time possible.

Measuring the Link Between Vaccines and Antimicrobial Resistance in Low Resource Settings – Limitations and Opportunities in Direct and Indirect Assessments and Implications for Impact Studies

The importance of vaccines in combatting antimicrobial resistance (AMR) is commonly accepted. Although scientific reasoning supports the putative connection between vaccines and reduction of AMR, reliably measuring the magnitude and effect of vaccines on antimicrobial resistance is inherently challenging, especially in low resource settings. We review the intrinsic challenges in estimating the effect of vaccines on AMR and discuss the limitations and opportunities in current methods from the host, pathogen, and environment perspectives. We highlight advantages and pitfalls in different epidemiological study designs with a specific focus on impact studies in low resource settings and suggest how these perspectives could be considered in future research.

Exploring antibiotic prescribing in public and private primary care settings in Singapore: a qualitative analysis informing theory and evidence-based planning for value-driven intervention design

BackgroundSingapore’s healthcare system presents an ideal context to learn from diverse public and private operational models and funding systems.AimTo explore processes underpinning decision-making for antibiotic prescribing, by considering doctors’ experiences in different primary care settings.MethodsThirty semi-structured interviews were conducted with 17 doctors working in publicly funded primary care clinics (polyclinics) and 13 general practitioners (GP) working in private practices (solo, small and large). Data were analysed using applied thematic analysis following realist principles, synthesised into a theoretical model, informing solutions to appropriate antibiotic prescribing.ResultsGiven Singapore’s lack of national guidelines for antibiotic prescribing in primary care, practices are currently non-standardised. Themes contributing to optimal prescribing related first and foremost to personal valuing of reduction in antimicrobial resistance (AMR) which was enabled further by organisational culture creating and sustaining such values, and if patients were convinced of these too. Building trusting patient-doctor relationships, supported by reasonable patient loads among other factors were consistently observed to allow shared decision-making enabling optimal prescribing. Transparency and applying data to inform practice was a minority theme, nevertheless underpinning all levels of optimal care delivery. These themes are synthesised into the VALUE model proposed for guiding interventions to improve antibiotic prescribing practices.These should aim to reinforce intrapersonal Values consistent with prioritising AMR reduction, and Aligning organisational culture to these by leveraging standardised guidelines and interpersonal intervention tools. Such interventions should account for the wider systemic constraints experienced in publicly funded high patient turnover institutions, or private clinics with transactional models of care. Thus, ultimately a focus on Liaison between patient and doctor is crucial. For instance, building in adequate consultation time and props as discussion aids, or quick turnover communication tools in time-constrained settings. Message consistency will ultimately improve trust, helping to enable shared decision-making. Lastly, Use of monitoring data to track and Evaluate antibiotic prescribing using meaningful indicators, that account for the role of shared decision-making can also be leveraged for change.ConclusionsThese VALUE dimensions are recommended as potentially transferable to diverse contexts, and the model as implementation tool to be tested empirically and updated accordingly.

Evaluating an antimicrobial stewardship programme implemented in an intensive care unit of a large academic hospital, using the RE-AIM framework.

The threat of antimicrobial resistance driven by inappropriate and unnecessary use of antimicrobials is a global issue of great concern. Evidence-based approaches to optimising antimicrobial prescribing to improve patient care while reducing the rate of antimicrobial resistance continue to be implemented worldwide. However, the successes or failures of implementation of such approaches are seldom evaluated. To evaluate the impact of an implemented antimicrobial stewardship programme (ASP) in reducing the spread of antimicrobial resistance in the intensive care unit (ICU) of a large academic hospital using the RE-AIM framework. A descriptive quasi-experimental study was conducted with adult patients who had been admitted to the ICU of an academic hospital in Johannesburg, South Africa. Data were extracted from patients' records using a structured questionnaire. Descriptive statistics of four RE-AIM dimensions (reach, effectiveness, adoption and implementation) and the overall impact of the implemented antimicrobial stewardship programme were calculated. From the 59 participant records, 21 patients (35.6%) developed hospital-acquired infections and all were prescribed antimicrobials during their stay in the ICU. Twenty-seven pathogens (bacterial species) were isolated from samples acquired from the patients, including Staphylococcus aureus (n=6; 22.2%), Escherichia coli (n=4; 14.8%), Acinetobacter baumannii (n=4; 14.8%) and Streptococcus pnuemoniae (n=3; 11.11%), as well as 10 other bacterial species (37.0%) including Corynebacterium species, Enterococcus faecium, Haemophilus influenzae, Klebsiella species, Clostridium difficile and Salmonella species. Of the 27 pathogens isolated, 19 (70.4 %) were resistant to the prescribed antimicrobials. The overall impact of the ASP implemented in the studied facility was 67.2%. An ASP requires both thorough implementation and leadership support to have an impact in the reduction of antimicrobial resistance. Lack of leadership support poses a significant challenge to sustainability. There is an urgent need for behavioural change in hospital leadership.

Impact of a surgical safety checklist on surgical site infections, antimicrobial resistance, antimicrobial consumption, costs and mortality

In 2010, following the recommendations of the World Health Organization (WHO), our hospital implemented a surgical safety programme centred around a surgical safety checklist. The aim of this study was to compare indicators of surgical site infection, antimicrobial consumption, antimicrobial resistance, costs and in-hospital mortality before (January 2006 to July 2010) and after (August 2010 to December 2014) implementation of the programme. A case-control study was carried out matching patients with surgical site infection (SSI) to surgical patients without infection to examine the impact of the intervention. Use of the surgical checklist was associated with a significant reduction in SSI. When comparing the two time periods, we also identified a reduction in infections due to micro-organisms in the ESKAPE group (from 90.7% to 73.9%, P<0.001), a reduction of SSI in patients with contaminated, infected and potentially contaminated wounds, and for those in whom perioperative antimicrobial prophylaxis was discontinued in less than 48 hours. Overall, there was a reduction in antimicrobial resistance, though there was increased resistance to carbapenems for, to glycopeptides for Enterococcus faecium, and to clindamycin for Staphylococcus aureus. We also detected increased antimicrobial consumption of second- and third-generation cephalosporins and clindamycin. We observed a reduction in hospital deaths from 6.4% to 3.2% (P=0.001), but we did not observe any reduction in costs. Implementation of a surgical checklist was an independent predictor of SSI reduction, and was also associated with a decrease in antimicrobial resistance and reduced in-hospital mortality.

WHO key access antibiotics prices, availability and affordability in private sector pharmacies in Pakistan

BackgroundPoor availability and unaffordability of key access antibiotics may increase antimicrobial resistance in the community by promoting inappropriate antibiotic selection and abridged therapy compliance.ObjectiveTo check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan.MethodologyA survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient’s affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook.ResultsThe mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day’s wage (median) if using OB and 0.4 day’s wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1).ConclusionThere is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.

Antimicrobial resistance of bacterial isolates from the clinical and hospital environment in Gaza Strip, Palestine: A review over 20-year

Antimicrobial resistance is a serious threatening problem associated with high morbidity and mortality. The majority of pathogenic bacteria show multiple drug resistance patterns. Thus, treatment of infections caused by those bacteria become ineffective. This paper evaluates, investigates, and discusses the existing situation of antimicrobial resistance in Gaza Strip, Palestine. The data of this review considered the published articles over the period 2002-2021. Search was conducted using Google scholar, Researchgate, and PubMed search engines. Thirty five articles were included. This review discussed studies done on antibiotic resistant bacteria found in a wide range of environments including clinical samples, foods, poultry, costal water, hospital wastewater, and hospital environments. The reported dissemination and spread of antibiotic resistant bacteria is influenced by several factors like inappropriate and unwise use of antibiotics as well as the un-regulated access of these antibiotics to the environment. Palestine is in urgent need to develop, strengthen, and implement antimicrobial stewardship policy, standard treatment guidelines, a local plan for containment and reduction of antimicrobial resistance, and research related to public health aspects of antimicrobial resistance at the community and hospital level. Keywords; Antimicrobial resistance, Gaza strip, Palestine