Implications Of Antimicrobial Resistance Research Articles

Sustainable Rain Solutions And Microbial Safety Research For Indian Water Crisis

Environmental Impact Awareness has always been the forefront of many surveys and solutions while trying to find the perfect know-it-all answer to the bigger question- “What do we have and What is getting depleted and finished?”. Water scarcity remains a pressing issue in arid and semi-arid regions of India, making rainwater harvesting a critical solution. This research investigates rainwater harvesting as a means to enhance water security, focusing on its benefits for water supply, flood risk reduction, and climate change mitigation. The paper outlines the stages of rainwater collection, transportation, and storage, emphasizing the technology required for active implementation while addressing sustainability concerns. Additionally, it reviews regulations such as the National Water Policy and microbial safety standards from the Bureau of Indian Standards (BIS) to ensure safe water. Findings on microbial testing, filtration technology, and community engagement for water conservation demonstrate a dual approach to water protection and public health. This study argues that rainwater harvesting not only serves as a water source but also has implications for antimicrobial resistance (AMR) in both potable and agricultural water. Ultimately, this work supports rainwater harvesting as a vital strategy for climate resilience and sustainable development in water-scarce regions

Community antibiotic consumption and associated factors in Lusaka district of Zambia: findings and implications for antimicrobial resistance and stewardship.

Antimicrobial resistance (AMR) is a global public health crisis. This study assessed the general public's consumption of antibiotics and associated factors in the Lusaka district of Zambia. This cross-sectional study was conducted among 2038 participants between December 2022 and January 2023. Data were analysed using Stata 13.0. Multivariable regression techniques were used to determine the factors that influenced antibiotic consumption. Of the 2038 participants, 53.4% were female, and 51.5% had attended at least secondary school. Antibiotic use was 99.2%, of which 40.9% were appropriately used. Overall, 79.1% of antibiotics were prescribed in hospitals, while 20.9% were used from leftovers and accessed without prescriptions. This study found that the appropriate use of antibiotics was associated with being female, being aged 35 years and above, attaining secondary school or tertiary education, having a monthly expenditure of 195 USD and above, being aware that antibiotics were not the same as painkillers, and being confident that when someone was hospitalized, they would get well. This study found that the appropriate use of antibiotics was low, and this is an urgent public health issue requiring community engagement in tackling AMR and adherence to treatment guidelines in healthcare facilities. Additionally, there is a need to implement and strengthen antimicrobial stewardship programmes in healthcare facilities to promote the rational use of antibiotics in Zambia. There is also a need to heighten community awareness campaigns and educational activities on the appropriate use of antibiotics.

Non-prescription antibiotics dispensing by community pharmacies: implications for antimicrobial resistance

Introduction: The non-prescription antibiotics dispensing (NPAD) from pharmacies is on the rise in low- and middle-income countries, which contributes to the emergence of antimicrobial resistance (AMR). This study was conducted with the objective to determine the community pharmacy personnel’s perspectives on NPAD and its implications for AMR. Methods: A questionnaire-based cross-sectional survey was conducted in Pakistan among 336 pharmacies. The data were analyzed using SPSS v21 and MedCalc for Windows v12.3.0. Modified Bloom’s cut-off point was utilized to categorize the participants’ overall knowledge, attitude, and practice. For univariable logistic regression analyses, odds ratio (OR) was calculated at 95% confidence interval (CI). For multivariable logistic regression analyses, adjusted OR was calculated at 95% CI. Spearman’s rank correlation coefficient test was used to assess the relationships among knowledge, attitude, and/or practice scores. Results: The majority of the respondents were staff pharmacists (45.5%). About four-fifths (78.9%) and half (50.9%) of the participants demonstrated moderate to good knowledge and practice, respectively. However, about only one-third (33.1%) had a moderate to good attitude. Staff pharmacists had higher odds of moderate to good knowledge (OR: 2.4, 95% CI: 1.2–4.7) and practice (OR: 2.3, 95% CI: 1.4–3.8). Total knowledge and practice (Spearman’s ρ: 0.280; P <0.001) and total attitude and practice (Spearman’s ρ: 0.299; P <0.001) scores were significantly correlated. Conclusion: The qualified pharmacists had satisfactory knowledge, attitude, and practices toward antibiotics. However, non-pharmacist staff lacked knowledge and had probable NPAD practice, which has a negative impact on public health. Regular refresher training, seminars, and strict enforcement of rules and regulations are essential.

Priority regions for eliminating open defecation in Africa: implications for antimicrobial resistance

AbstractSanitation, which offers safe and effective methods for waste disposal, is important for development. However, in Africa and other developing regions, the prevalent practice of open defecation (OD) impedes attaining the sustainable development goals (SDGs). This research delves into the analysis of OD in Africa and proposes a three-tier priority system, comprising critical, high, and medium areas, through which developmental endeavours can be targeted. To achieve this, the study utilizes data from demographic and health surveys (DHS) and the World Bank. The rates of OD at country and sub-country/region levels were calculated to define the priority system, and regression analyses were used to determine predictors of OD practice. The findings are that Nigeria, Ethiopia, Niger, the Democratic Republic of Congo, Burkina Faso, and Chad have a high number of people struggling with open defecation. In addition, disparities in access to proper sanitation facilities were identified among impoverished individuals and those residing in rural areas. After adjusting for education and residence, the poorest are 43 times (95% confidence interval 42.443–45.290) more likely to practice open defecation in comparison with the wealthiest. Consequently, wealth index is a pivotal factor in eradicating open toileting. To address this pressing issue in Africa, it is imperative to prioritize evidence-based targeted interventions that concentrate on regions and communities urgently needing improved sanitation infrastructure and programmes. Special attention should be paid to West Africa since many of its communities are in the critical category. Poverty and inequality must be addressed and investments in sanitation infrastructure, behavioural change promotion, and support multistakeholder collaborations should be encouraged. To evaluate OD interventions and monitor health impact, variables such as antimicrobial resistance (AMR) should be included in important health surveys (e.g. DHS). This study is the largest meta-data analyses of OD in Africa detailing drivers and communities that should be prioritised on sanitation interventions.

Seasonality of antimicrobial use in Dutch food-producing animals.

Due to globally increasing antimicrobial resistance (AMR), it is pivotal to understand factors contributing to antimicrobial use (AMU) to enable development and implementation of AMR-reducing interventions. Therefore, we explored seasonal variations of systemic AMU in food-producing animals in the Netherlands. Dutch surveillance data from January 2013 to December 2018 from cattle, pig, and broiler farms were used. AMU was expressed as the number of Defined Daily Dosages Animal per month (DDDA/animal-month) per farm by animal sector, antimicrobial line (first, second, and third), antimicrobial class, and farm type. Seasonality of AMU was analyzed using Generalized Additive Models (GAMs) with DDDA/animal-month as outcome variable, and year and month as independent variables. Year and month were modelled as smooth terms represented with penalized regression splines.Significant seasonality of AMU was found in the cattle and pig sectors, but not in broilers. Significant seasonality of AMU was found mainly for first-line antimicrobials. In the cattle sector, a significant increase during winter was found for the use of amphenicols (an increase of 23.8%) and long-acting macrolides (an increase of 3.4%). In the pig sector, seasonality of AMU was found for pleuromutilins (p<0.001) with an increase of 20% in October-November. The seasonality of pleuromutilins was stronger in sows/piglets (an increase of 47%) than in fattening pigs (16% increase). Only in fattening pigs, the use of amphenicols showed a significant seasonality with an increase of 11% during winter (P<0.001). AMU in cattle and pig sectors shows seasonal variations likely caused by seasonality of diseases. In broilers, no AMU seasonality was observed, possibly due to the controlled environment in Dutch farms. In the context of the one health concept, future studies are necessary to explore whether this seasonality is present in other populations and whether it has implications for antimicrobial resistance in humans through the food chain.

Revolutionizing biomedicine: Metal-organic frameworks combating multi-drug resistance

Antimicrobial resistance (AMR) has emerged as one of the major risks to public health, seriously compromising efforts to prevent and treat chronic diseases. The trends of global AMR show no evidence of slowing down, despite various measures implemented in the past few decades. The main causes of the rise of resistant bacteria are thought to be the misuse and overuse of various antimicrobial drugs in the healthcare sector as well as in the agricultural business. One of the key strategies to combat AMR is the creation of new antimicrobial agents. When pitted against the capacity for the evolution of multi-drug resistant (MDR) bacteria, it indicates that the science world is lagging behind in the race to develop alternative strategies to fight AMR. AMR has been listed as among the top ten worldwide public health threats. There is no perfect cure, and the drawbacks of current approaches call for more advancement in the field of antimicrobials. Recent advancements in nanotechnology position them as hopeful therapeutics and a powerful substitute for synthetic drugs and traditional antibiotics. The antimicrobial category recently gained better properties of the metal–organic framework (MOF). Many MOFs are biocompatible and have antimicrobial effects on a variety of species due to their porous architecture which also enables them to carry biomolecules and medications for synergistic antimicrobial effects. This feature letter discusses the causes as well as implications of AMR and also offers insight into a novel-emerging class of mesoporous nanostructures of MOF as the potential candidate to combat the spread of AMR.

Multispecies coinfections and presence of antibiotics shape resistance and fitness costs in a pathogenic bacterium.

Increasing antimicrobial resistance (AMR) poses a challenge for treatment of bacterial diseases. In real life, bacterial infections are typically embedded within complex multispecies communities and influenced by the environment, which can shape costs and benefits of AMR. However, knowledge of such interactions and their implications for AMR in vivo is limited. To address this knowledge gap, we investigated fitness-related traits of a pathogenic bacterium (Flavobacterium columnare) in its fish host, capturing the effects of bacterial antibiotic resistance, coinfections between bacterial strains and metazoan parasites (fluke Diplostomum pseudospathaceum) and antibiotic exposure. We quantified real-time replication and virulence of sensitive and resistant bacteria and demonstrate that both bacteria can benefit from coinfection in terms of persistence and replication, depending on the coinfecting partner and antibiotic presence. We also show that antibiotics can benefit resistant bacteria by increasing bacterial replication under coinfection with flukes. These results emphasize the importance of diverse, inter-kingdom coinfection interactions and antibiotic exposure in shaping costs and benefits of AMR, supporting their role as significant contributors to spread and long-term persistence of resistance.

Decision Challenges for Managing Acute Paediatric Infections: Implications for Antimicrobial Resistance.

Overprescribing of antibiotics in paediatrics accounts for a significant proportion of inappropriate antibiotic use in human healthcare, thereby contributing to the global health emergency of antimicrobial resistance. Antimicrobial stewardship efforts are complicated by the unique social dynamics in paediatric healthcare, with a specific challenge being the prominent role of parents and carers who act as intermediaries between prescribers and paediatric patients. In this Perspective article concentrating on healthcare of the United Kingdom, we describe this complicated interplay of different decision stakeholders (patients, parents and prescribers), outline four dimensions of decision challenges (social, psychological, systemic and specific diagnostic and treatment challenges) and provide a number of theory-based strategies for supporting different stakeholders during the decision process, ultimately with the aim of improving antimicrobial stewardship. Key decision challenges for patients and carers include limited knowledge and experience of managing infections, which were exacerbated during the COVID-19 pandemic and frequently result in health anxiety and inappropriate health-seeking behaviours. Challenges for medical prescribers span societal pressures from prominent patient litigation cases, cognitive biases, and system pressures to specific diagnostic problems (e.g., age limitations of current clinical scoring systems). Strategies for mitigating decision challenges in paediatric infection management will need to include a range of context- and stakeholder-specific actions, including improvements of integrated care and public health education as well as better clinical decision tools and access to evidence-based guidelines.

Antibiotic dispensing practices during COVID-19 and implications for antimicrobial resistance (AMR): parallel mystery client studies in Uganda and Tanzania

BackgroundOver-the-counter antibiotic access is common in low-and-middle-income countries and this may accelerate antimicrobial resistance. Our study explores critical aspects of the drug seller–client interaction and antibiotic dispensing patterns for simulated COVID-19 symptoms during the pandemic in two study sites in Tanzania and Uganda, countries with different government responses to the pandemic.MethodsResearch assistants posing as clients approached different types of drug sellers such as pharmacies (Pharms), drug shops (DSs), and accredited drug dispensing outlets (ADDOs) in Mwanza, Tanzania (nPharms = 415, nADDOs = 116) and Mbarara, Uganda (nPharms = 440, nDSs = 67), from June 10 to July 30, 2021. The mystery clients held no prescription and sought advice for simulated COVID-19 symptoms from the drug sellers. They documented the quality of their interaction with sellers and the type of drugs dispensed.ResultsAdherence to COVID-19 preventive measures and vigilance to COVID-19 symptoms was low in both sites but significantly higher in Uganda than in Tanzania. A higher percentage of drug sellers in Mbarara (Pharms = 36%, DSs = 35%, P-value = 0.947) compared to Mwanza (Pharms = 9%, ADDOs = 4%, P-value = 0.112) identified the client’s symptoms as possibly COVID-19. More than three-quarters of drug sellers that sold prescription-only medicines in both Mbarara (Pharms = 86%, DSs = 89%) and Mwanza (Pharms = 93%, ADDOs = 97%) did not ask the MCs for a prescription. A relatively high percentage of drug sellers that sold prescription-only medicines in Mwanza (Pharms = 51%, ADDOs = 67%) compared to Mbarara (Pharms = 31%, DSs = 42%) sold a partial course without any hesitation. Of those who sold antibiotics, a higher proportion of drug sellers in Mbarara (Pharms = 73%, DSs = 78%, P-value = 0.580) compared to Mwanza (Pharms = 40% ADDOs = 46%, P-value = 0.537) sold antibiotics relevant for treating secondary bacterial infections in COVID-19 patients.ConclusionOur study highlights low vigilance towards COVID-19 symptoms, widespread propensity to dispense prescription-only antibiotics without a prescription, and to dispense partial doses of antibiotics. This implies that drug dispensing related to COVID-19 may further drive AMR. Our study also highlights the need for more efforts to improve antibiotic stewardship among drug sellers in response to COVID-19 and to prepare them for future health emergencies.

Knowledge, attitudes and practices regarding antimicrobial use and resistance among healthcare seekers in two tertiary hospitals in Ghana: a quasi-experimental study

ObjectiveTo evaluate knowledge of antimicrobial resistance (AMR), to study how the judgement of health value (HVJ) and economic value (EVJ) affects antibiotic use, and to understand if access to information...

Implications of Antimicrobial Resistance during Acne Treatment: Review Article

Implications of Antimicrobial Resistance during Acne Treatment: Review Article

Next-generation Sequencing for Surveillance of Antimicrobial Resistance and Pathogenicity in Municipal Wastewater Treatment Plants.

The World Health Organization (WHO) ranks antimicrobial resistance (AMR) and various pathogens among the top 10 health threats. It is estimated that by 2050, the number of human deaths due to AMR will reach 10 million annually. On the other hand, several infectious outbreaks such as SARS, H1N1 influenza, Ebola, Zika fever, and COVID-19 have severely affected human populations worldwide in the last 20 years. These recent global diseases have generated the need to monitor outbreaks of pathogens and AMR to establish effective public health strategies. This review presents AMR and pathogenicity associated with wastewater treatment plants (WWTP), focusing on Next Generation Sequencing (NGS) monitoring as a complementary system to clinical surveillance. In this regard, WWTP may be monitored at three main points. First, at the inlet (raw wastewater or influent) to identify a broad spectrum of AMR and pathogens contained in the excretions of residents served by sewer networks, with a specific spatio-temporal location. Second, at the effluent, to ensure the elimination of AMR and pathogens in the treated water, considering the rising demand for safe wastewater reuse. Third, in sewage sludge or biosolids, their beneficial use or final disposal can represent a significant risk to public health. This review is divided into two sections to address the importance and implications of AMR and pathogen surveillance in wastewater and WWTP, based on NGS. The first section presents the fundamentals of surveillance techniques applied in WWTP (metataxonomics, metagenomics, functional metagenomics, metaviromics, and metatranscriptomics). Their scope and limitations are analyzed to show how microbiological and qPCR techniques complement NGS surveillance, overcoming its limitations. The second section discusses the contribution of 36 NGS research papers on WWTP surveillance, highlighting the current situation and perspectives. In both sections, research challenges and opportunities are presented.

Experiences of antibiotic use among Brazilian healthcare users: An exploratory study.

This article analyzes experiences of antibiotic use and bacterial infections among Primary Health Care users of the Brazilian Unified Health System (SUS) and the possible implications for antimicrobial resistance (AMR). The aim is to map aspects that shape users' lay knowledge regarding antibiotics use and AMR. This is an exploratory study, which consists primarily of individual in-depth interviews with 19 respondents. Recurrent interview topics were coded and analysed according to thematic content analysis. Our findings show users' lived experiences constitute three dimensions related to users' previous antibiotic use: (1) lay knowledge about medicines; (2) previous bacterial infectionsand (3) communication during the consultation. Lay knowledge encompasses the users' understanding of how antibiotics work in comparison to other drugs and experimentations they make with medication. Users' narratives about bacterial infections are divided into situations of urinary tract infectionsand antibiotic treatments for other conditions. Communication during the consultation is mainly characterized by a lack of shared knowledge and trust in the doctor-patient relationship. Users bring together knowledge learned from their own experiences to create the rationale, which shapes how they understand antibiotic use, bacterial infections and medical advice. These experiences are interwoven with information received from healthcare professionals (HPs) on these topics, creating a scenario that goes beyond professional information about antibiotic use. Users have knowledge about medication, antibiotics use and bacterial infection but do not have room to share it with HP, allowing lived experiences to take precedence over professional information. Users ascribe symbolic meanings to antibiotics creating a lay knowledge frame, even if this knowledge is not scientifically correct. The personal experiences of bacterial infections and their treatment are also an important source of knowledge about antibiotic use and AMR among users. Users demand from their HPs both trust and willingness to listen to their health narratives and experiences. By considering lay knowledge as part of the assessment of a user's health condition, rather than dismissing it as erroneous and therefore unworthy of attention, HPs may enhance the compliance of users. Patients or community members did not participate in the design stage of the study. Primary Care patients were invited to participate as respondents of in-depth interviews, which were carried out by the first author at a Primary Care Unit (PCU) in the suburb of Campo Limpo, Southern region of São Paulo, Brazil. Patients were interviewed after reading and signing a Free and Informed Consent Form, holding with them a copy of the Form. Among the final activities of the project, a feedback session at the same PCU is planned to report on the results of the study. All respondents will have the opportunity to contribute further information regarding their antibiotic use and exchange knowledge and experiences on antimicrobial resistance.

A Qualitative Study of Antibiotic Use Practices in Intensive Small-Scale Farming in Urban and Peri-Urban Blantyre, Malawi: Implications for Antimicrobial Resistance.

The routine use of antimicrobials in meat production has been identified as a driver of antimicrobial resistance (AMR) in both animals and humans. Significant knowledge gaps exist on antibiotic use practices in farming, particularly in sub-Saharan Africa. This paper sought to generate in-depth understanding of household antibiotic use practices in food animals in urban- and peri-urban Blantyre. We used a qualitative research methodology focusing on households that kept scavenging animals and those engaged in small-scale intensive farming of food animals. Methods used were: medicine-use surveys with 130 conducted with a range of households; in-depth interviews (32) with a range of participants including farmers, community based veterinary health workers and veterinary shop workers; and stakeholder interviews (17) with policy makers, regulators, and academics. Six months of ethnographic fieldwork was also undertaken, with households engaged in farming, veterinary officers and veterinary stores. Our findings suggest antibiotic use in animals was more common in households that used small-scale intensive farming techniques, but rare in households that did not. For farmers engaged in small-scale intensive farming, antibiotics were often considered vital to remain solvent in a precarious economic and social environment, with limited access to veterinary services. A complex regulatory framework governed the import, prescription, and administration of antibiotics. Veterinary stores provided easy access to antibiotics, including colistin, an antibiotic on the WHO's critically important antibiotics for human health. Our work suggests that the high dependence on antibiotics for small-scale intensive farming may contribute to the growth of drug resistant infections in Malawi. The socio-economic drivers of antibiotic use mean that interventions need to take a holistic approach to address the high dependence on antibiotics. Key interventions could include improving farmers' access to affordable veterinary services, providing information about appropriate antibiotic use including withdrawal periods and feed supplementation, as well as improvements in regulation (nationally and internationally) and enforcement of current regulations. Taken together these approaches could lead to antibiotic use being optimised in feed animals.

Antimicrobial resistance: revisiting the mechanisms of resistance

Resistance to antibiotics persists as a critical challenge in public health. Currently, the emergence of multi-drug resistant (MDR) bacteria is a primary concern globally, resulting in a dramatic increase in epidemiological relevance and importance of nosocomial and chronic infections. Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae has recently been classified as critical in the World Health Organization (WHO) priority pathogens. Among these bacterial pathogens, resistance seems to be a natural trait. The acquisition and development of resistance by bacteria is through several mechanisms. The genetic background and intrinsic resistance mechanisms largely contribute to competitive advantage and resistance in a highly resistant pool. The acquisition of resistance genes driven by mobile genetic elements (MGE) and several biochemical mechanisms also plays a central role in resistance development among pathogenic bacteria. This review discussed the recent underlying multiple resistance mechanisms among the priority pathogens. This review also provides an up-to-date regional epidemiological data and implications of antimicrobial resistance. Given the severity of infections caused by these bacteria, their less susceptibility to the available antimicrobials, and the limited antimicrobial arsenal to treat these pathogens, current insight on resistance mechanisms becomes timely and highly relevant. This information will help develop better therapeutic strategies against resistance microbes, especially those of urgent priority.

Potential Application of Combined Therapy with Lectins as a Therapeutic Strategy for the Treatment of Bacterial Infections.

Antibiotic monotherapy may become obsolete mainly due to the continuous emergence of resistance to available antimicrobials, which represents a major uncertainty to human health. Taking into account that natural products have been an inexhaustible source of new compounds with clinical application, lectins are certainly one of the most versatile groups of proteins used in biological processes, emerging as a promising alternative for therapy. The ability of lectins to recognize carbohydrates present on the cell surface allowed for the discovery of a wide range of activities. Currently the number of antimicrobials in research and development does not match the rate at which resistance mechanisms emerge to an effective antibiotic monotherapy. A promising therapeutic alternative is the combined therapy of antibiotics with lectins to enhance its spectrum of action, minimize adverse effects, and reduce resistance to treatments. Thus, this review provides an update on the experimental application of antibiotic therapies based on the synergic combination with lectins to treat infections specifically caused by multidrug-resistant and biofilm-producing Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We also briefly discuss current strategies involving the modulation of the gut microbiota, its implications for antimicrobial resistance, and highlight the potential of lectins to modulate the host immune response against oxidative stress.

Influence of Human Eating Habits on Antimicrobial Resistance Phenomenon: Aspects of Clinical Resistome of Gut Microbiota in Omnivores, Ovolactovegetarians, and Strict Vegetarians.

The use of xenobiotics in food production and how food intake is carried out in different cultures, along with different eating habits (omnivorism (ON), ovolactovegetarianism (VT), and strict vegetarianism (VG)) seem to have implications for antimicrobial resistance, especially in the human gut microbiota. Thus, the aim of this study was to evaluate aspects of the clinical resistome of the human gut microbiota among healthy individuals with different eating habits. Volunteers were divided into 3 groups: n = 19 omnivores (ON), n = 20 ovolactovegetarians (VT), and n = 19 strict vegetarians (VG), and nutritional and anthropometric parameters were measured. Metagenomic DNA from fecal samples was used as a template for PCR screening of 37 antimicrobial resistance genes (ARG) representative of commonly used agents in human medicine. The correlation between eating habits and ARG was evaluated. There were no significant differences in mean caloric intake. Mean protein intake was significantly higher in ON, and fiber and carbohydrate consumption was higher in VG. From the screened ARG, 22 were detected. No clear relationship between diets and the occurrence of ARG was observed. Resistance genes against tetracyclines, β-lactams, and the MLS group (macrolides, lincosamides, and streptogramins) were the most frequent, followed by resistance genes against sulfonamides and aminoglycosides. Vegetables and minimally processed foods seem to be the main source of ARG for the human gut microbiota. Although eating habits vary among individuals, the open environment and the widespread ARG from different human activities draw attention to the complexity of the antimicrobial resistance phenomenon which should be addressed by a One Health approach.

High global consumption of potentially inappropriate fixed dose combination antibiotics: Analysis of data from 75 countries.

Antibiotic fixed dose combinations (FDCs) can have clinical advantages such as improving effectiveness and adherence to therapy. However, high use of potentially inappropriate FDCs has been reported, with implications for antimicrobial resistance (AMR) and toxicity. We used a pharmaceutical database, IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS®), to estimate sales of antibiotic FDCs from 75 countries in 2015. Antibiotic consumption was estimated using standard units (SU), defined by IQVIA as a single tablet, capsule, ampoule, vial or 5ml oral suspension. For each FDC antibiotic, the approval status was assessed by either registration with the United States Food and Drug Administration (US FDA) or inclusion on the World Health Organization (WHO) Essential Medicines List (EML). A total of 119 antibiotic FDCs were identified, contributing 16.7 x 109 SU, equalling 22% of total antibiotic consumption in 2015. The most sold antibiotic FDCs were amoxicillin-clavulanic acid followed by trimethoprim/sulfamethoxazole and ampicillin/cloxacillin. The category with the highest consumption volume was aminopenicillin/β-lactamase inhibitor +/- other agents. The majority of antibiotic FDCs (92%; 110/119) were not approved by the US FDA. Of these, the most sold were ampicillin/cloxacillin, cefixime/ofloxacin and metronidazole/spiramycin. More than 80% (98/119) of FDC antibiotics were not compatible with the 2017 WHO EML. The countries with the highest numbers of FDC antibiotics were India (80/119), China (25/119) and Vietnam (19/119). There is high consumption of FDC antibiotics globally, particularly in middle-income countries. The majority of FDC antibiotic were not approved by either US FDA or WHO EML. International initiatives such as clear guidance from the WHO EML on which FDCs are not appropriate may help to regulate the manufacturing and sales of these antibiotics.

Characterization of the MurT/GatD complex in Mycobacterium tuberculosis towards validating a novel anti-tubercular drug target.

ObjectivesIdentification and validation of novel therapeutic targets is imperative to tackle the rise of drug resistance in tuberculosis. An essential Mur ligase-like gene (Rv3712), expected to be involved in cell-wall peptidoglycan (PG) biogenesis and conserved across mycobacteria, including the genetically depleted Mycobacterium leprae, was the primary focus of this study.MethodsBiochemical analysis of Rv3712 was performed using inorganic phosphate release assays. The operon structure was identified using reverse-transcriptase PCR and a transcription/translation fusion vector. In vivo mycobacterial protein fragment complementation assays helped generate the interactome.ResultsRv3712 was found to be an ATPase. Characterization of its operon revealed a mycobacteria-specific promoter driving the co-transcription of Rv3712 and Rv3713. The two gene products were found to interact with each other in vivo. Sequence-based functional assignments reveal that Rv3712 and Rv3713 are likely to be the mycobacterial PG precursor-modifying enzymes MurT and GatD, respectively. An in vivo network involving Mtb-MurT, regulatory proteins and cell division proteins was also identified.ConclusionsUnderstanding the role of the enzyme complex in the context of PG metabolism and cell division, and the implications for antimicrobial resistance and host immune responses will facilitate the design of therapeutics that are targeted specifically to M. tuberculosis.

Can the One Health Approach Save Us from the Emergence and Reemergence of Infectious Pathogens in the Era of Climate Change: Implications for Antimicrobial Resistance?

Climate change has become a controversial topic in today’s media despite decades of warnings from climate scientists and has influenced human health significantly with the increasing prevalence of infectious pathogens and contribution to antimicrobial resistance. Elevated temperatures lead to rising sea and carbon dioxide levels, changing environments and interactions between humans and other species. These changes have led to the emergence and reemergence of infectious pathogens that have already developed significant antimicrobial resistance. Although these new infectious pathogens are alarming, we can still reduce the burden of infectious diseases in the era of climate change if we focus on One Health strategies. This approach aims at the simultaneous protection of humans, animals and environment from climate change and antimicrobial impacts. Once these relationships are better understood, these models can be created, but the support of our legislative and health system partnerships are critical to helping with strengthening education and awareness.