A Survey Assessing Antimicrobial Prescribing at United Nations Relief and Works Agency Primary Health Care Centers in Jordan.

Antimicrobial resistance (AMR) is a public health emergency. There is insufficient information on AMR in the context of humanitarian settings. An understanding of behavioral and institutional-level factors can strengthen antimicrobial stewardship. This study used a semistructured questionnaire to assess both knowledge, attitudes, and practices (KAP) on antimicrobial use, resistance and stewardship, and options to improving prescribing, among prescribers at the Primary Healthcare facilities of the United Nations' Relief and Works Agency Jordan field office. Responses to the KAP questions were evaluated using the Capability, Opportunity, Motivation, Behavior (COM-B) framework and Bloom's cutoffs. For each framework component, Bloom's cutoffs and interpretations were as follows: ≥ 80%, "good"; 60-79%, "moderate"; and < 60%, "poor." Fourteen options to improve prescribing were each assessed using 5-point Likert scales from very unhelpful to very helpful, aggregated by helpful and very helpful and ranked as follows: > 90%, best/most acceptable; > 80-90%, acceptable; and 70-80% as maybe acceptable/good. The questionnaire response rate was 59% (37/63) with a completion rate of 92% (34/37). Aggregate scores for real knowledge on AMR was 97%; opportunity to improve prescribing 88%; and motivation 16%-participants did not believe that there was a connection between their prescribing and AMR or that they had a key role in helping control AMR. Good options (74% aggregate score) to improving prescribing were the availability of guidelines and resistance data. There was good knowledge of AMR and good opportunities, but poor motivation for rational prescribing or behavioral change. There is a clinical need for AMR data to promote rational antibiotic prescribing.

Patient Access in 14 High-Income Countries to New Antibacterials Approved by the US Food and Drug Administration, European Medicines Agency, Japanese Pharmaceuticals and Medical Devices Agency, or Health Canada, 2010-2020.

BACKGROUND: Inaccessibility of medicines in low- and middle-income countries is a frequent challenge. Yet it is typically assumed that high-income countries have complete access to the full arsenal of medicines. This study tests this assumption for new antibacterials, which are saved as a last resort in order to prevent the development of resistance, resulting in insufficient revenues to offset costs. Prior studies report only regulatory approval, missing the important lag that occurs between approval and commercial launch, although some antibiotics never launch in some countries. METHODS: We identified all antibacterials approved and launched in the G7 and 7 other high-income countries in Europe for the decade beginning 1 January 2010, using quantitative methods to explore associations. RESULTS: Eighteen new antibacterials were identified. The majority were accessible in only 3 countries (United States, United Kingdom, and Sweden), with the remaining 11 high-income countries having access to less than half of them. European marketing authorization did not lead to automatic European access, as 14 of the antibacterials were approved by the European Medicines Agency but many fewer were commercially launched. There was no significant difference in access between "innovative" and "noninnovative" antibacterials. Median annual sales in the first launched market (generally the United States) for these 18 antibiotics were low, $16.2M. CONCLUSIONS: Patient access to new antibacterials is limited in some high-income countries including Canada, Japan, France, Germany, Italy, and Spain. With low expected sales, companies may have decided to delay or forego commercialization due to expectations of insufficient profitability.

Assessing Antimicrobial Resistance, Utilization, and Stewardship in Yemen: An Exploratory Mixed-Methods Study.

Antimicrobial resistance (AMR), largely driven by irrational use of antimicrobials, is a global, multifaceted problem calling for a complete understanding of all contributory factors for effective containment. In conflict settings, war-wounds and malnutrition can combine with existing social determinants to increase demand for antibiotics, compounding irrational use. In this study, we focus on Yemen, a low-income country with active conflict for the last 5 years, and analyze the current status of awareness and stewardship efforts regarding AMR. We performed a survey of prescribers/physicians and pharmacists to describe perceptions of AMR prevalence, antibiotic use practices, and stewardship in Yemen, supported by a nonsystematic scoping literature review and a key informant interview. Participants (96%, N = 54) reported a perceived high AMR prevalence rate. Prescribers (74%, 20/27) reported pressure to prescribe broad-spectrum antibiotics. In the majority of cases (81%, 22/27), antimicrobial sensitivity tests (AST) were not performed to inform antibiotic choice. The main barrier to AST was cost. Most pharmacists (67%, 18/27) sold antibiotics without prescriptions. Amoxicillin (including amoxicillin-clavulanate) was the most-commonly prescribed (63%, 17/27) or dispensed (81%, 22/27) antibiotic. AST was rated the least important solution to AMR in Yemen. While there was awareness of a high AMR rate, stewardship is poor in Yemen. We note that barriers to the use of AST could be addressed through the deployment of reliable, affordable, quality rapid diagnostics, and AST kits. Compulsory continuing education emphasizing the use of AST to guide prescribing and patients' awareness programs could help avoid irrational use.

Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism.

The global obesity epidemic has necessitated the search for better intervention strategies including the exploitation of the health benefits of some gut microbiota and their metabolic products. Therefore, we examined the gut microbial composition and mechanisms of interaction with the host in relation to homoeostatic energy metabolism and pathophysiology of dysbiosis-induced metabolic inflammation and obesity. We also discussed the eubiotic, health-promoting effects of probiotics and prebiotics as well as epigenetic modifications associated with gut microbial dysbiosis and risk of obesity. High-fat/carbohydrate diet programmes the gut microbiota to one predominated by Firmicutes (Clostridium), Prevotella and Methanobrevibacter but deficient in beneficial genera/species such as Bacteroides, Bifidobacterium, Lactobacillus and Akkermansia. Altered gut microbiota is associated with decreased expression of SCFA that maintain intestinal epithelial barrier integrity, reduce bacterial translocation and inflammation and increase expression of hunger-suppressing hormones. Reduced amounts of beneficial micro-organisms also inhibit fasting-induced adipocyte factor expression leading to dyslipidaemia. A low-grade chronic inflammation (metabolic endotoxaemia) ensues which culminates in obesity and its co-morbidities. The synergy of high-fat diet and dysbiotic gut microbiota initiates a recipe that epigenetically programmes the host for increased adiposity and poor glycaemic control. Interestingly, these obesogenic mechanistic pathways that are transmittable from one generation to another can be modulated through the administration of probiotics, prebiotics and synbiotics. Though the influence of gut microbiota on the risk of obesity and several intervention strategies have been extensively demonstrated in animal models, application in humans still requires further robust investigation.

Bacterial antibiotic resistance development and mutagenesis following exposure to subinhibitory concentrations of fluoroquinolones in vitro: a systematic review of the literature.

BACKGROUND: Understanding social and scientific drivers of antibiotic resistance is critical to help preserve antibiotic efficacy. These drivers include exposure to subinhibitory antibiotic concentrations in the environment and clinic. OBJECTIVES: To summarize and quantify the relationship between subinhibitory fluoroquinolone exposure and antibiotic resistance and mutagenesis to better understand resistance patterns and mechanisms. METHODS: Following PRISMA guidelines, PubMed, Web of Science and Embase were searched for primary in vitro experimental studies on subinhibitory fluoroquinolone exposure and bacterial antibiotic resistance and mutagenesis, from earliest available dates through to 2018 without language limitation. A specifically developed non-weighted tool was used to assess risk of bias. RESULTS: Evidence from 62 eligible studies showed that subinhibitory fluoroquinolone exposure results in increased resistance to the selecting fluoroquinolone. Most increases in MIC were low (median minimum of 3.7-fold and median maximum of 32-fold) and may not be considered clinically relevant. Mechanistically, resistance is partly explained by target mutations but also changes in drug efflux. Collaterally, resistance to other fluoroquinolones and unrelated antibiotic classes also develops. The mean ± SD quality score for all studies was 2.6 ± 1.8 with a range of 0 (highest score) to 7 (lowest score). CONCLUSIONS: Low and moderate levels of resistance and efflux changes can create an opportunity for higher-level resistance or MDR. Future studies, to elucidate the genetic regulation of specific resistance mechanisms, and increased policies, including surveillance of low-level resistance changes or genomic surveillance of efflux pump genes and regulators, could serve as a predictor of MDR development.

Access to essential cardiovascular medicines for children: a pilot study of availability, price and affordability in Nigeria.

Policies to improve access to medicines for children in low- and middle-income countries, such as Nigeria, should consider the growing threat of non-communicable diseases. The aim of this pilot study was to scope availability, price and affordability of essential cardiovascular medicines for children in selected states in Nigeria. The study was a descriptive longitudinal survey conducted in three phases. Availability was determined as percentage of facilities having the medicine on the survey date. Medicines with good availability (>80%) were noted. Prices were cross-referenced against international Reference Prices and the Nigerian National Health Insurance Scheme Prices. Affordability was calculated using the Least-Paid Government Worker method. For medicines compounded to improve availability, a model for calculating affordability was proposed. In Phase I, the availability of all 17 strengths of the cardiovascular medicines or diuretics listed in the Essential Medicines List for Children (2015) were surveyed in two conveniently selected states using the WHO/HAI questionnaire. Data were collected from 17 hospitals and pharmacies. Phases II and III focused on tablet formulations (enalapril, furosemide, hydrochlorothiazide and spironolactone) in three purposively selected state capitals: Lagos, Abuja and Yenagoa. In Phase II, 11 private pharmacies were surveyed in December 2016: Phase III tracked price changes in Abuja and Yenagoa in August 2018. Only furosemide and hydrochlorothiazide tablets had good availability. Oral liquids were unavailable. Prices for four generic oral tablets were 2-16× higher than the International Reference Prices; prices for two of these did not change significantly over the study period. Affordable medicines were generic furosemide and hydrochlorothiazide tablet. Where a fee is charged, compounded medicines were also not affordable. While the small sample sizes limit generalization, this study provides indicative data suggesting that prices for cardiovascular medicines remain high and potentially unaffordable in the private sector in these selected states, and when compounded. Regular systematic access surveys are needed.

Bacterial antibiotic resistance development and mutagenesis following exposure to subminimal inhibitory concentrations of fluoroquinolones in vitro: a systematic literature review protocol.

INTRODUCTION: Antibiotic resistance (AR) is among the most pressing global health challenges. Fluoroquinolones are a clinically important group of antibiotics that have wide applicability in both humans and animals. While many drivers of AR are known, the impact of medicine quality on AR remains largely unknown. The aim of this review is to systematically evaluate the evidence of the impact of in vitro subinhibitory antibiotic exposure, a major tenet of substandard antibiotics, on the development of AR and mutagenesis, using fluoroquinolones as a case study. METHODS AND ANALYSIS: EMBASE, Web of Science and PubMed will be systematically searched for primary experimental in vitro studies, from earliest available dates within each database (1947, 1965 and 1966, respectively) through 2018, related to subinhibitory fluoroquinolone exposure and AR. A specifically developed non-weighted tool will be used to critically assess the evidence. Subgroup analyses will be performed for different variables and outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are to be collected. The completed systematic review will be disseminated through conference meeting presentations and a peer-reviewed publication.