No description available.

No description available.

Antimicrobial resistance (AMR) is concerning because it limits antimicrobial drug treatment options. AMR occurs by the overuse and misuse of antimicrobial drugs. In environmental settings, AMR can disseminate from places of high use, which leads to increased exposure to humans and animals. A previous study from our laboratory group showed extended-spectrum cephalosporinase-producing Escherichia coli/Klebsiella pneumoniae were isolated from fecal samples obtained in rural Cambodian community settings. Based on these isolates, this study has two aims. The first aim was characterization of selected Cambodian isolates with random amplification polymorphic DNA (RAPD) and antibiotic susceptibility test. From RAPD, the selected six isolates are diverse, except for C61 and C66 bacteria isolates with potential clonality. Additionally, the selected isolates are multidrug resistant (MDR) with reduced susceptibility to beta-lactams and fluoroquinolones. The second aim was to assess two developed methodologies, multiplex automated genome engineering (MAGE) and One-Step Curing Plasmid, by validation in bacteria laboratory strain and development for six Cambodian isolates. To modify AMR genetic elements, MAGE uses pMA7-SacB for homologous recombination with oligos for chromosomal gene disruption. Meanwhile, One-Step Curing Plasmid uses pFREE with the CRISPR/Cas9 system for plasmid and self-curing. Validation showed that MAGE can modify 8% of E. coli MG1655 with lacZ control screening oligos and almost 90% are cured from pFREE. Selected Cambodian isolates have antibiotic-resistance plasmids of IncR or IncFII replicon. For usage in Cambodian isolates, pFREE was modified to be pCAM-FREE by cloning IncR and IncFII plasmid as gRNA1 and gRNA5, respectively. Sequencing results showed pCAM-FREE have gRNA5. In conclusion, our study managed to characterize selected Cambodian isolates as MDR and diverse. In a laboratory strain, MAGE and One-Step Curing Plasmid are functional methods. Furthermore, pCAM-FREE was constructed to target IncFII and in the future, MAGE and pCAM-FREE could be tested in Cambodian isolates.

Magister Pharmaceuticae - MPharm / Antimicrobial resistance is a global concern associated with increased morbidity and mortality. It has been estimated that, by 2050, the continuous escalation of antimicrobial resistance, globally, will result in more deaths per year, compared to cancer and diabetes. The direct and indirect impact of ineffective antibiotics, and therefore, antimicrobial resistance, will be hardest felt by low and middle-income countries, as the financial burden will be too great to manage. Carbapenems are considered the last line of antimicrobials to treat multidrug-resistant bacterial infections. They are the preferred choice to treat infections, presenting with extended-spectrum beta-lactamases (ESBL) producing Enterobacteriacea. Various strains of bacteria that have become resistant, due to the selective pressure, as a result of carbapenem over use, are referred to as Carbapenem-resistant Enterobacteriaceae (CRE). / 2022

The increase in antibiotic resistance continues to pose a public health risk as very few new antibiotics are being produced, and bacteria resis- tant to currently prescribed antibiotics is growing. Within a typical hospital setting, one may find patients colonized with bacteria resistant to a single an- tibiotic, or, of a more emergent threat, patients may be colonized with bacteria resistant to multiple antibiotics. Precautions have been implemented to try to prevent the growth and spread of antimicrobial resistance such as a reduction in the distribution of antibiotics and increased hand washing and barrier pre- ventions; however, the rise of this resistance is still evident. As a result, there is a new movement to try to re-examine the need for the development of new antibiotics. In this paper, we use mathematical models to study the possible benefits of implementing a new antibiotic in this setting; through these models, we examine the use of a new antibiotic that is distributed in various ways and how this could reduce total resistance in the hospital. We compare several dif- ferent models in which patients colonized with both single and dual-resistant bacteria are present, including a model with no additional treatment proto- cols for the population colonized with dual-resistant bacteria as well as models including isolation and/or treatment with a new antibiotic. We examine the benefits and limitations of each scenario in the simulations presented.

Magister Scientiae (Biodiversity and Conservation Biology) / Combating antimicrobial resistant infections caused by nosocomial pathogens poses a major public health problem globally. The widespread use of broad-spectrum antibiotics for the treatment of wound infections has led to the appearance of multidrug-resistant (MDR) microbes which further exacerbates the growth of microbes amongst patients. It may result in prolonged debility of the patient and an increase in healthcare costs due to prolonged hospital stays and expensive treatment regimens to avoid patient-patient transmission. Therefore, it is imperative that alternative sources of treatment to antimicrobial use in wound infections needs to be developed in order to inhibit or kill resistant microbes and to provide point of care medical treatment to the less fortunate at an affordable cost.

No description available.

No description available.

Antimicrobial resistance (AMR) is rapidly becoming a public health issue, as more and more infectious bacteria become resistant to our known antibiotics. Suggested reasons for the proliferation of these strains are misuse and overuse of antimicrobials, especially on an industrial level, in agriculture, livestock and aquaculture. These resistances are not unique for pathogenic bacteria but originates in nature where complicated systems of microbes interact with each other. Freshwater environments hold special interest as they provide drinking water, have unique biodiversity, and provide other ecosystem services. Soil environments have the most diverse microbial communities and are often the source of new discoveries in microbial functions and AMR interactions. Since the vast majority of microbes can’t be maintained in pure culture or replicated in the laboratory setting, metagenomic methods have proven to be vital for understanding the diversity and occurrence of AMR in the environment that would otherwise have remained unexplored and unaccounted for. By producing metagenomic pipelines that utilize parallel computing to handle vast amounts of data, a catalogue of AMR in 390 samples mainly from Scandinavia was created from two datasets. One of the datasets had been previously processed and published, while the other was managed from raw reads to metagenomic assembled bins. This revealed a difference in the distribution of resistance mechanisms that microbes utilize to achieve AMR based on lifestyle and that AMR can be found in most taxa as well as in any freshwater and soil environments.

BACKGROUND: India—one of the most significant antibiotic users in the world with a high burden of antibiotic resistance—does not have a formal antibiotic surveillance system. No formal studies exist on the sub-national differences in antibiotic use in India except for small hospital or community-based studies. Informed by the WHO Global Action Plan, India developed a national action plan; however only two states have state action plans so far. This suggests that it is important to understand existing antibiotic consumption patterns, sub- national differences and trends over time, and the determinants of antibiotic use so that evidence-informed action plans and programs can be developed in India. AIM: To understand the changing landscape of antibiotic use in India and contribute to relevant policy and programmatic interventions that can improve the appropriate use of antibiotics in the country. Specific objectives included examining the use of systemic antibiotic consumption at the national level, analyzing geographical and temporal variations across states between 2011 and 2019, and understanding the determinants of antibiotic consumption. Additionally, we examined Kerala as a case study to understand the use and availability of data in designing, implementing, and monitoring the state antibiotic action plan. METHODOLOGY: First, we conducted a cross-sectional analysis of antibiotic use in 2019 using the WHO Access-Watch-Reserve (AWaRe) and Defined Daily Doses (DDD) matrices at the national level across product type (Fixed-Dose Combinations [FDCs]; and single formulations [SF]), essentiality (listed in the national list of essential medicines [NLEM]; and not listed), and central regulatory approval status (approved and unapproved). Second, we analyzed trends in consumption rates and patterns at the national, state, and groups of states at different levels of health achievements (‘high focus’ [HF]; and ‘non-high focus’ [nHF]) and compared the appropriateness of use between states and state groups. Third, using a cross-sectional, time series (panel) dataset on antibiotic use, per-capita GDP, per-capita government spending on health, girls' tertiary education enrollment ratio, measles vaccination coverage, and lower respiratory tract infection incidence for the period 2011- 2019, we conducted a quasi- experimental fixed-effects analysis to understand the critical determinants of antibiotic use. Finally, we conducted key-informant interviews and document analysis to understand the use of data in policy formulation, implementation, monitoring, and evaluation of the Kerala state action plan. RESULTS: India's per-capita private-sector antibiotic consumption rate was lower than global rates, but the country has a high consumption rate of broad-spectrum antibiotics, FDCs discouraged by WHO, formulations outside NLEM in FDCs, and unapproved formulations. The overall rate increased from 2011 to 2016 and decreased between 2016 and 2019, registering a net decrease of 3.6%. State consumption rates varied widely— with HF states reporting lower rates. The inappropriate use increased over the years, the share of Access antibiotics decreased (13.1%), and the access-to-watch ratio declined (from 0.59 to 0.49). HF and nHF states showed convergence in the share of the Access and the Access-Watch ratio, while they showed divergence in the use of WHO Discouraged FDCs. The most critical independent determinant of antibiotic use was government spending on health—for every US$12.9 increase in per-capita government spending on health, antibiotic use decreased by 461.4 doses per 1000 population per year after adjusting for other factors. Economic progress (increase in per-capita GDP) and social progress (increase in girls' higher education) were also found to reduce antibiotic use independently. The qualitative case study showed that stakeholders understand and express interest in generating and using data for decision- making, and the action plan document mentions some basic monitoring plans. However, a monitoring and evaluation framework is missing, there is a lack of engagement with the private sector, and there is a lack of understanding among key government policymakers on the importance of using data for surveillance and policy implementation. CONCLUSION AND IMPLICATIONS: There is significant and increasing inappropriate antibiotic use in India's private sector, accounting for 85-90% of total antibiotic use. Increased government spending on health is critical in reducing private-sector antibiotic use. The dearth of data on public sector use is a significant challenge in understanding the total consumption rate. Developing a monitoring and evaluation system through stakeholder engagement is necessary for Indian States to inform, monitor, and evaluate effective antibiotic action plans. We need global efforts to improve the science and methods to measure antibiotic use. / 2023-08-30T00:00:00Z