Project description:Although the COVID-19 pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance crisis. In dermatology, antibiotics are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of antimicrobial resistance and review resistance concerns related to dermatology-relevant bacterial pathogens.
Project description:Antimicrobial resistance (AMR) decreases the effectiveness of antimicrobials to treat bacterial infections in humans and animals. The increased occurrence of AMR in bacterial population in humans, animals, and the environment requires the measures to combat a rising global health crisis. The aim of this research was to present current knowledge on AMR in a system map and to identify potential explanations of former identified variables significantly associated with AMR. This study applies a systems thinking approach and uses feedback loops to visualize the interconnections between human, animal, and environmental components in a circular AMR system map model. First, a literature review focusing on AMR and socioeconomic factors, wicked problem, and system change was carried out, which was then processed in a system map to conceptualize the present core challenges of AMR via feedback loops. Second, to investigate possible underlying values of the society and those that influence humans' behavior in the present AMR system, an iceberg model was established. Third, leverage points were assessed to estimate which kinds of interventions would have the greatest effect to mitigate AMR in the system. The present AMR system map implies the potential to identify and visualize important risk factors that are direct or indirect drivers of AMR. Our results show that the tool of system mapping, which interconnects animals, humans, and environment in one model, can approach AMR holistically and be used to assess potential powerful entry points for system wide interventions. This study shows that system maps are beneficial as a model to predict the relative effect of different interventions and adapt to rapidly changing environments in a complex world. Systems thinking is considered as a complementing approach to the statistical thinking, and further research is needed to evaluate the use of such tools for the development and monitoring of interventions.
Project description:The expanding impact of chronic kidney disease (CKD) due to pandemic diabetes mellitus is recounted emphasizing its epidemiology that has induced global socioeconomic stress on health care systems in industrialized nations now attempting to proffer optimal therapy for end stage renal disease (ESRD). Strategies to delay and perhaps prevent progression of diabetic nephropathy from minimal proteinuria through nephrotic range proteinuria and azotemia to ESRD appear to have decreased the rate of persons with diabetes who develop ESRD. For those with ESRD attributed to diabetes, kidney transplantation affords better survival and rehabilitation than either hemodialysis or peritoneal dialysis. It is likely that advances in genetics and molecular biology will suggest early interventions that will preempt diabetic complications including renal failure.
Project description:Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by the WHO as high-priority pathogens given their association with morbidity and mortality and the scarce number of effective antibiotic treatments. In Spain, the frequency of OXA-48 CPE outbreaks is higher than in other European countries, representing the major resistance mechanism of CPEs. Horizontal transfer of plasmids and poor effective antibiotic treatment are additional threats to the correct prevention and control of these hospital outbreaks. One of the most important risk factors is antibiotic pressure, specifically carbapenem overuse. We explored the use of these antibiotics in Spain and analyzed the frequency, characteristics and prevention of CPE outbreaks. Future antibiotic stewardship programs along with specific preventive measures in hospitalized patients must be reinforced and updated in Spain.
Project description:Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n=23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded ?-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to ?-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.
Project description:The cross-sectional approach to HIV incidence estimation overcomes some of the challenges with longitudinal cohort studies and has been successfully applied in many settings around the world. However, the cross-sectional approach does rely on an initial training data set to develop and calibrate the statistical methods to be used in cross-sectional surveys. The problem addressed in this paper is that the initial training data set may, over time, not reflect the current target population of interest because of evolution of the epidemic. For example, the mismatch between the target population and the initial data set could occur because of increasing use of anti-retroviral therapy among HIV-infected persons throughout the world. We developed methods to adjust the initial training data set with the goal that the adjusted data sets better reflect the target population. These adjustment procedures could help avoid the time and expense of collecting a completely new training data set from the current target population. We report the results of a simulation study to evaluate the procedures. We applied the methods to a dataset of HIV subtype B infection. The adjustment procedures could be applicable in situations other than cross-sectional incidence estimation where complex statistical analyses are to be conducted using an initial data set but those results may not be directly transportable to a new target population of interest. The approach we have proposed could offer a practical and cost-effective way to apply cross-sectional incidence methods to new target populations as the epidemic evolves.
Project description:Influenza is a highly contagious and debilitating disease that imposes an excess burden of complications and mortality. Antiviral therapy is the primary intervention for treatment and post-exposure prophylaxis (PEP) of influenza. Amantadine and rimantadine are members of the M2 class of antiviral agents and are moderately effective in influenza management. However, their utility is compromised by high levels of resistance, tolerability concerns and a lack of efficacy against influenza B. An alternative class of agents, the neuraminidase inhibitors (NIs), represent the most advanced form of antiviral therapy available, and act by specifically inhibiting the neuraminidase enzymes that are present on all influenza subtypes. Two NIs, oseltamivir and zanamivir, are currently available for clinical use. Oseltamivir, the most widely used NI, is administered orally as a prodrug (oseltamivir carboxylate) and systemically distributed to all potential infection sites. Zanamivir, a second NI, is administered by inhalation via a disk inhaler and deposited primarily in the respiratory tract. When administered within 48 hours of symptom onset, both agents significantly reduce illness duration and symptom severity, and decrease the rate of influenza-associated complications. With oseltamivir, greater benefits are detected with earlier treatment initiation (<12 hours). In PEP, both NIs effectively protect the close contacts of index cases from symptomatic influenza. Oseltamivir and zanamivir are generally well tolerated and associated with a low level of resistance. Emerging evidence supports the activity of both NIs against the H5N1avian influenza infection, which is a pandemic candidate. However, the WHO currently recommends the use of oseltamivir for the management of suspected cases, given the systemic nature of the H5N1 challenge. Ongoing studies are exploring the effectiveness of oseltamivir, zanamivir and other NIs for pandemic management.
Project description:Direct lytic agents (DLAs) are novel antimicrobial compounds with unique mechanisms of action based on rapid cell wall destabilization and bacteriolysis. DLAs include two classes of purified polypeptides-lysins (peptidoglycan hydrolase enzymes) and amurins (outer membrane targeting peptides). Their intended use is to kill bacteria in a manner that is complimentary to and synergistic with traditional antibiotics without selection for DLA resistance. Lysins were originally described as having activity against Gram-positive pathogens and of those, exebacase, is the first to have advanced into Phase 3 of clinical development. Recently, both engineered and native DLAs have now been described with potent bactericidal activity against a range of Gram-negative pathogens, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Importantly, novel DLAs targeting Gram-negatives, including the lysin CF-370 and the amurin peptides, are active in biological matrices (blood/serum) and, as such, offer promise for therapeutic use as systemically administered agents for the treatment of life-threatening invasive infections. In this review, DLAs are discussed as potential new classes of antimicrobial biologics that can be used to treat serious systemic infections.
Project description:The impact of the coronavirus disease (COVID-19) pandemic on antimicrobial resistance (AMR) is a major concern. To compare the number of patients and isolation rate of antimicrobial-resistant bacteria before and after the beginning of the COVID-19 pandemic using the comprehensive national surveillance data. We utilized comprehensive surveillance data, collected in the Japan Nosocomial Infections Surveillance programme, which included a total of 16.7 million samples of 5.9 million tested patients from >1300 hospitals. We compared the number of patients and isolation rate of five bacteria between 2019 and 2020, including antimicrobial-susceptible and -resistant bacteria of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The number of patients and isolation rate of S. aureus and meticillin-resistant S. aureus decreased slightly; those of S. pneumoniae and penicillin-resistant S. pneumoniae decreased by 60%; and those of third-generation cephalosporin-resistant K. pneumoniae increased. The isolation rate of the remaining bacteria apparently increased, although the number of patients decreased. This was due to a substantial decrease in the total number of tested patients (the denominator of the isolation rate), which was larger than that of the number of patients (the numerator of the isolation rate). Consistent results were obtained when the same data were re-aggregated using the procedure of the World Health Organization Global Antimicrobial Resistance Surveillance System, demonstrating the general importance of this problem. Surveillance data during the COVID-19 pandemic must be carefully interpreted based on examination of the numerator, denominator and background factors that affect the denominator.