Threat Of Resistance Research Articles

The Impact of Bamboo Consumption on the Spread of Antibiotic Resistance Genes in Giant Pandas.

The spread of antibiotic resistance genes (ARGs) in the environment exacerbates the contamination of these genes; therefore, the role plants play in the transmission of resistance genes in the food chain requires further research. Giant pandas consume different bamboo parts at different times, which provides the possibility of investigating how a single food source can affect the variation in the spread of ARGs. In this study, metagenomic analysis and the Comprehensive Antibiotic Resistance Database (CARD) database were used to annotate ARGs and the differences in gut microbiota ARGs during the consumption of bamboo shoots, leaves, and culms by captive giant pandas. These ARGs were then compared to investigate the impact of bamboo part consumption on the spread of ARGs. The results showed that the number of ARGs in the gut microbiota of the subjects was highest during the consumption of bamboo leaves, while the variety of ARGs was highest during the consumption of shoots. Escherichia coli, which poses a higher risk of ARG dissemination, was significantly higher in the leaf group, while Klebsiella, Enterobacter, and Raoultella were significantly higher in the shoot group. The ARG risk brought by bamboo shoots and leaves may originate from soil and environmental pollution. It is recommended to handle the feces of giant pandas properly and regularly monitor the antimicrobial and virulence genes in their gut microbiota to mitigate the threat of antibiotic resistance.

Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.

Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin β7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.

Phage Therapy, a Salvage Treatment for Multidrug-Resistant Bacteria Causing Infective Endocarditis.

Infective endocarditis (IE) is defined as an infection of the endocardium, or inner surface of the heart, most frequently affecting the heart valves or implanted cardiac devices. Despite its rarity, it has a high rate of morbidity and mortality. IE generally occurs when bacteria, fungi, or other germs from another part of the body, such as the mouth, spread through the bloodstream and attach to damaged areas in the heart. The epidemiology of IE has changed as a consequence of aging and the usage of implantable cardiac devices and heart valves. The right therapeutic routes must be assessed to lower complication and fatality rates, so this requires early clinical suspicion and a fast diagnosis. It is urgently necessary to create new and efficient medicines to combat multidrug-resistant bacterial (MDR) infections because of the increasing threat of antibiotic resistance on a worldwide scale. MDR bacteria that cause IE can be treated using phages rather than antibiotics to combat MDR bacterial strains. This review will illustrate how phage therapy began and how it is considered a powerful potential candidate for the treatment of MDR bacteria that cause IE. Furthermore, it gives a brief about all reported clinical trials that demonstrated the promising effect of phage therapy in combating resistant bacterial strains that cause IE and how it will become a hope in future medicine.

Antimicrobial Stewardship in the Hospital Setting: A Narrative Review.

The increasing global threat of antibiotic resistance, which has resulted in countless fatalities due to untreatable infections, underscores the urgent need for a strategic action plan. The acknowledgment that humanity is perilously approaching the "End of the Miracle Drugs" due to the unjustifiable overuse and misuse of antibiotics has prompted a critical reassessment of their usage. In response, numerous relevant medical societies have initiated a concerted effort to combat resistance by implementing antibiotic stewardship programs within healthcare institutions, grounded in evidence-based guidelines and designed to guide antibiotic utilization. Crucial to this initiative is the establishment of multidisciplinary teams within each hospital, led by a dedicated Infectious Diseases physician. This team includes clinical pharmacists, clinical microbiologists, hospital epidemiologists, infection control experts, and specialized nurses who receive intensive training in the field. These teams have evidence-supported strategies aiming to mitigate resistance, such as conducting prospective audits and providing feedback, including the innovative 'Handshake Stewardship' approach, implementing formulary restrictions and preauthorization protocols, disseminating educational materials, promoting antibiotic de-escalation practices, employing rapid diagnostic techniques, and enhancing infection prevention and control measures. While initial outcomes have demonstrated success in reducing resistance rates, ongoing research is imperative to explore novel stewardship interventions.

Antimicrobial surveillance: A 20-year history of the SMART approach to addressing global antimicrobial resistance into the future

Antimicrobial resistance (AMR) is a major global public health threat, particularly affecting patients in resource-poor settings. Comprehensive surveillance programmes are essential to reducing the high mortality and morbidity associated with AMR and are integral to informing treatment decisions and guidelines, appraising the effectiveness of intervention strategies, and directing development of new antibacterial agents. Various surveillance programmes exist worldwide, including those administered by government bodies or funded by the pharmaceutical industry. One of the largest and longest running industry-sponsored AMR surveillance programme is the Study for Monitoring Antimicrobial Resistance Trends (SMART), which recently completed its 20th year. The SMART database has grown to almost 500000 isolates from over 200 sites in more than 60 countries, encompassing all major geographic regions and including many sites in low- and middle-income countries. The SMART surveillance programme has evolved in scope over time, including additional antibacterial agents, pathogens and infection sites, in line with changing epidemiology and medical need. Surveillance data from SMART and similar programmes have been used successfully to detect emerging resistance threats and AMR patterns in specific countries and regions, thus informing national and local clinical treatment guidelines. The SMART database can be accessed readily by physicians and researchers globally, which may be especially valuable to those from countries with limited healthcare resources, where surveillance and resistance data are rarely collected. Continued participation from as many sites as possible worldwide and maintenance of adequate funding are critical factors to fully realising the potential of large-scale AMR surveillance programmes into the future.

Population structure and antimicrobial resistance among Klebsiella isolates sampled from human, animal, and environmental sources in Ghana: a cross-sectional genomic One Health study

One Health approaches to address the increasing threat of antimicrobial resistance (AMR) are gaining attention. However, data on the distribution and movement of bacteria and their AMR-associated genes between clinical and non-clinical sources are scarce, especially from low-income and middle-income countries. We aimed to analyse Klebsiella isolates from various sources in Ghana and compare the prevalence of AMR with datasets from two other countries. We conducted a cross-sectional genomic One Health study. Multiple clinical, environmental, and animal sources were sampled from 78 locations (eg, hospitals, residential areas, and farms) in and around Tamale, Ghana. Clinical samples were collected through routine screening and in cases of suspected infection between March 15 and Sept 15, 2019, and samples from the wider environment were collected during a dedicated sampling effort between the dates of Aug 19, 2018, and Sept 26, 2019. Sampling locations were approximately evenly distributed from the centre of the city and steadily outwards to capture both rural and urban locations. Samples with positive growth for Klebsiella were included. Isolates of Klebsiella were obtained from the samples using Simmons citrate agar medium and characterised by antimicrobial susceptibility testing and whole-genome sequencing. A comparative analysis with Klebsiella population surveys from Pavia, Italy, and Tromsø, Norway, was performed. AMR-associated and virulence genes were detected, and the population distribution of these genes was studied. Of 957 samples collected around Tamale, Ghana, 620 were positive for Klebsiella spp. 573 Klebsiella isolates were successfully sequenced, of which 370 were Klebsiella pneumoniae. Only two hospital isolates were carbapenem-resistant. Extended-spectrum β-lactamase (ESBL) genes were relatively common among the Ghanaian clinical isolates but rare in the environmental samples. Prevalence of ESBL genes in human-hospital disease samples was 64% (14 of 22 isolates) in Ghana and 44% (four of nine isolates) in Italy, and prevalence in human-hospital carriage samples was 7% (eight of 107) in Ghana and 13% (54 of 428) in Italy; the prevalence was higher in human-hospital disease samples than in human-hospital carriage samples in both countries, and prevalence across both samples in both countries was higher than in Norway. Ghanaian isolates showed evidence of high recombination rates (recombination events compared with point mutations [r/m] 9·455) and a considerable accessory gene overlap with isolates from Italy and Norway. Although several AMR-associated gene classes were observed relatively frequently in non-clinical sources, ESBL, carbapenemase, and virulence genes were predominantly present only in hospital samples. These results suggest that interventions should be focused on clinical settings to have the greatest effect on the prevalence and dissemination of AMR-associated genes. European Research Council (742158), Academy of Finland EuroHPC grant, Trond Mohn Foundation (BATTALION grant), and Wellcome Trust.

Early-life antibiotic usage and impact on the gut microbiota, including emergence of antimicrobial resistant Enterococcus

The early-life microbiota is an ‘immature’ and highly dynamic microbial ecosystem, which is central to infant health. Both perinatal and postnatal factors can impact the gut microbiota, with antibiotics proposed to cause short and longer-term disturbances. Antibiotics not only impact microbial community composition but also contribute to the overall antibiotic resistance profile, i.e. the ‘resistome’, and they may also enhance carriage of multi-drug-resistant bacteria. Given high antibiotic prescription practices in pregnant women and newborns this also contributes to the global threat of antimicrobial resistance. This review summarises the current literature on antibiotic usage and how this may impact the developing gut microbiota during early-life, including the influence of horizontal gene transfer on contributions to pathogenicity and resistance of gut bacteria. We also focus on Enterococcus spp. given their high levels in infants and their link with opportunistic infections that are a significant cause of morbidity and mortality during early-life. Finally, a perspective on the importance to antibiotic stewardship, and harnessing the microbiota itself for anti-infection therapies for reducing antibiotic usage are also covered.

The threat of antimicrobial resistance in surgical care: the surgeon's role and ownership of antimicrobial stewardship.

The threat of antimicrobial resistance in surgical care: the surgeon's role and ownership of antimicrobial stewardship.

The resistomes of rural and urban pigs and poultry in Ghana.

There is limited knowledge on the bacteriome and resistome in livestock in Africa and the potential influence of the animal husbandry practices and scale has also been scantly explored. We quantified and characterized the antimicrobial resistance gene (ARG) pools (resistomes) and bacteriome in 30 pigs and 60 poultry samples (free-range: rural and urban, and industrialized) across Ghana using Resfinder and Silva databases and compared them to similar data from pigs and poultry from nine European countries. The pig and poultry were very different in ARG and bacterial abundance and composition. The bacterial communities in the Ghanaian samples also differed substantially from the European samples, especially driven by a much higher abundance of Subdoligranulum in both animals. We found lower ARG loads in Ghanaian pigs compared to European counterparts. Among poultry, urban free-range samples exhibited lower ARG abundances compared to the lowest European levels, while rural free-range samples were comparable to the European average, and industrialized samples showed higher ARG abundances. Despite major differences in abundance, the resistome composition of Ghanaian urban, rural, and industrialized poultry samples was similar. Contrasts with European samples were mainly driven by increased abundances of different tetracycline resistance genes in Ghanaian samples, and increased abundances of ARGs encoding resistance to macrolides, beta-lactams, and trimethoprim in Europe. Among pig samples, the main differences were caused by ARGs encoding resistance to nitroimidazoles, beta-lactams, and macrolides in European samples. This study is, to the best of our knowledge, the first report on the resistome measured using metagenomics in livestock from Sub-Saharan Africa. IMPORTANCE To the best of our knowledge, this is the first report on the resistomes that are measured using metagenomics in livestock from Sub-Saharan Africa. We find notable differences in the microbiomes between both pigs and poultry, and those also varied markedly compared to similar samples from Europe. However, for both animal species, the same bacterial taxa drove such differences. In pigs and urban free-range poultry, we find a very low abundance of antimicrobial resistance genes (ARGs), whereas rural free-range poultry displayed similarity to the European average, and industrialized poultry exhibited higher levels. These findings show how different African livestock bacterial communities and resistomes are from their European counterparts. They also underscore the importance of continued surveillance and investigation into antimicrobial resistance across diverse ecosystems, contributing significantly to global efforts toward combating the threat of antibiotic resistance.

Comprehensive profiling and risk assessment of antibiotic resistance genes in a drinking water watershed by integrated analysis of air-water-soil

The prevalence of antibiotic resistance genes (ARGs) in diverse habitats threatens public health. Watersheds represent critical freshwater ecosystems that interact with both the soil and atmosphere. However, a holistic understanding of ARGs distribution across these environmental media is currently inadequate. We profiled ARGs and bacterial communities in air-water-soil in the same watershed area during four seasons using high-throughput qPCR and 16S rRNA gene sequencing. Our findings demonstrated that aminoglycoside resistance genes (58.5%) were dominant in water, and multidrug resistance genes (55.2% and 54.2%) were dominant in soil and air. Five ARGs and nineteen bacterial genera were consistently detected in all samples, were named as shared genes or bacteria. Co-occurrence Network analysis revealed the co-occurrence module of resistance genes, mobile genetic elements (MGEs), and potential bacterial hosts, indicating that shared genes and bacteria may persist and co-spread across different environmental media. The risk assessment framework, based on ARGs’ abundance, detection rate, and mobility, identified 33 high-risk ARGs. This is essential to evaluate the health risks of ARGs and to develop strategies to limit the threat of antibiotic resistance. Our study offers new insights into the risks associated with ARGs in the environment and suggests that ARGs may depend on specific bacterial cohabitants that co-exist with MGEs to facilitate their spread across environmental interfaces.

Model nematodes as a practical innovation to promote high throughput screening of natural products for anthelmintics discovery in South Asia: Current challenges, proposed practical and conceptual solutions

With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity. Focusing on South Asia, which produces one of the world’s highest research outputs in NP and NP-based anthelmintic discovery, we find that limited basic research and funding, a lack of awareness of the utility of model organisms, poor industry-academia partnerships and lack of technological innovations greatly limit anthelmintics research in the region. Here we propose that utilizing model organisms including the free-living nematode Caenorhabditis elegans, that can potentially allow rapid target identification of novel anthelmintics, and Oscheius tipulae, a closely related, free-living nematode which is found abundantly in soil in hotter temperatures, could be a much-needed innovation that can enable cost-effective and efficient HTS of NPs for discovering compounds with anthelmintic/antiparasitic potential in South Asia and other tropical regions that historically have devoted limited funding for such research. Additionally, increased collaborations at the national, regional and international level between parasitologists and pharmacologists/ethnobotanists, setting up government-industry-academia partnerships to fund academic research, creating a centralized, regional collection of plant extracts or purified NPs as a dereplication strategy and HTS library, and holding regional C. elegans/O. tipulae-based anthelmintics workshops and conferences to share knowledge and resources regarding model organisms may collectively promote and foster a NP-based anthelmintics landscape in South Asia and beyond.

Biofilm producer multi drug resistance alert bugs in ventilator associated pneumonia patients. Threat to antibiotic era and future concern

Background Emerging threat of drug resistance among Bacteria causing ventilator-associated pneumonia (VAP) has resulted in higher hospital costs, longer hospital stays, and increased hospital mortality. Biofilms in the endotracheal tube of ventilated patients act as protective shield from host immunity for bacterial growth and emerge them as multidrug resistant. Aim To know the prevalence of various bacterial isolates causing VAP, ability to form biofilm and their antibiotic susceptibility pattern. Material & Methods This study was conducted in the department of Microbiology in collaboration with the Respiratory Medicine department for a period of one year (November 2018-19). Endotracheal aspirate (ETA) along with 1 cm tube tip from clinically confirmed VAP patients were processed as per the standard microbiological procedure for the detection of bacterial biofilm formation and their antimicrobial resistance pattern. Statistical Analysis: Data was statistically evaluated using SPSS-PC-20 version. ‘P’ value less than 0.05, considered statistically significant. Results 72 patients with CPIS score > 6 were clinically confirmed as VAP. Various Bacteria isolated were Klebsiella pneumoniae in 52 (53%), Escherichia coli 16 (16.3%), Pseudomonas aeruginosa 14 (14.2%), Acinetobacter spp. 8 (8.1%), Proteus mirabilis 6 (6.1%) and Pseudomonas luteola 2 (2%). All bacterial isolates were processed for their ability to form biofilm, 86 (87.7%) were biofilm producers (BFP) while 12 (12.2%) were biofilm non-producers (BFNP). Conclusion Bacterial etiology, prolonged intubation, biofilm formation, and drug resistance have ramification on outcome of VAP. Keywords: Ventilator associated pneumonia (VAP), CPIS score, Biofilm formation, Tissue culture plate method (TCP), Antimicrobial drug resistance (AMR)

Caught Between a Well-Intentioned State and a Hostile Federal System: Local Implementation of Inclusive Immigrant Policies.

In the United States, inclusive state-level policies can advance immigrant health and health care access by extending noncitizens' access to public benefits, workplace rights, and protections from immigration enforcement. Although state policies carry promise as structural population health interventions, there has been little examination of their implementation at the local level. Local jurisdictions play multiple roles in state policy implementation and possess distinct immigration climates. Examining the local implementation of state immigrant policy can address challenges and opportunities to ensure the health benefits of inclusive policies are realized equitably across states' regions. To examine the local implementation of state immigrant policies, we selected a purposive sample of California counties with large immigrant populations and distinct social and political dynamics and conducted and analyzed in-depth interviews with 20 community-based organizations that provided health, safety net, and other services. We found that there were tensions between the inclusionary goals of state immigrant policies and local anti-immigrant climates and federal policy changes. First, there were tensions between state policy goals and resistance from local law enforcement agencies and policymakers (e.g., Board of Supervisors). Second, because of the ongoing threats from federal immigration policies, there was a mismatch between the services and resources provided by state policies and local community needs. Finally, organizations that served immigrants were responsible for contributing to policy implementation but lacked resources to meet community needs while countering local resistance and federal policy threats. This study contributes knowledge regarding the challenges that emerge after state immigrant policies are enacted. The tensions among state immigrant policies, local immigration climates, and federal policy changes indicate that state immigrant policies are not implemented equally across state communities, resulting in challenges and limited benefits from policies for many immigrant communities.

Escherichia coli cells are primed for survival before lethal antibiotic stress.

Non-genetic factors can cause significant fluctuations in gene expression levels. Regardless of growing in a stable environment, this fluctuation leads to cell-to-cell variability in an isogenic population. This phenotypic heterogeneity allows a tiny subset of bacterial cells in a population called persister cells to tolerate long-term lethal antibiotic effects by entering into a non-dividing, metabolically repressed state. We occasionally noticed a high variation in persister levels, and to explore this, we tested clonal populations starting from a single cell using a modified Luria-Delbrück fluctuation test. Although we kept the conditions same, the diversity in persistence level among clones was relatively consistent: varying from ~60- to 100- and ~40- to 70-fold for ampicillin and apramycin, respectively. Then, we divided and diluted each clone to observe whether the same clone had comparable persister levels for more than one generation. Replicates had similar persister levels even when clones were divided, diluted by 1:20, and allowed to grow for approximately five generations. This result explicitly shows a cellular memory passed on for generations and eventually lost when cells are diluted to 1:100 and regrown (>seven generations). Our result demonstrates (1) the existence of a small population prepared for stress ("primed cells") resulting in higher persister numbers; (2) the primed memory state is reproducible and transient, passed down for generations but eventually lost; and (3) a heterogeneous persister population is a result of a transiently primed reversible cell state and not due to a pre-existing genetic mutation. IMPORTANCE Antibiotics have been highly effective in treating lethal infectious diseases for almost a century. However, the increasing threat of antibiotic resistance is again causing these diseases to become life-threatening. The longer a bacteria can survive antibiotics, the more likely it is to develop resistance. Complicating matters is that non-genetic factors can allow bacterial cells with identical DNA to gain transient resistance (also known as persistence). Here, we show that a small fraction of the bacterial population called primed cells can pass down non-genetic information ("memory") to their offspring, enabling them to survive lethal antibiotics for a long time. However, this memory is eventually lost. These results demonstrate how bacteria can leverage differences among genetically identical cells formed through non-genetic factors to form primed cells with a selective advantage to survive antibiotics.

Antimicrobial Resistance: Is There a 'Light' at the End of the Tunnel?

In recent years, with the increases in microorganisms that express a multitude of antimicrobial resistance (AMR) mechanisms, the threat of antimicrobial resistance in the global population has reached critical levels. The introduction of the COVID-19 pandemic has further contributed to the influx of infections caused by multidrug-resistant organisms (MDROs), which has placed significant pressure on healthcare systems. For over a century, the potential for light-based approaches targeted at combatting both cancer and infectious diseases has been proposed. They offer effective killing of microbial pathogens, regardless of AMR status, and have not typically been associated with high propensities of resistance development. To that end, the goal of this review is to describe the different mechanisms that drive AMR, including intrinsic, phenotypic, and acquired resistance mechanisms. Additionally, the different light-based approaches, including antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and ultraviolet (UV) light, will be discussed as potential alternatives or adjunct therapies with conventional antimicrobials. Lastly, we will evaluate the feasibility and requirements associated with integration of light-based approaches into the clinical pipeline.

Helicobacter pylori Infections in Children.

In the context of epidemiology, host response, disease presentation, diagnosis, and treatment management, the manifestation of Helicobacter pylori (H. pylori) infection diverges between children and adults. H. pylori infection stands out as one of the most prevalent bacterial infections globally, and its prevalence in both children and adults is decreasing in many developing countries but some still struggle with a high prevalence of pediatric H. pylori infection and its consequences. The majority of infected children are asymptomatic and pediatric studies do not support the involvement of H. pylori in functional disorders such as recurrent abdominal pain. The pathophysiology of H. pylori infection relies on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors. This interaction gives rise to diverse gastritis phenotypes, which subsequently influence the potential development of various gastroduodenal pathologies. In clinical settings, the diagnosis of this infection in childhood requires an upper gastrointestinal endoscopic exam with mucosal biopsy samples for histology and culture, or Polymerase Chain Reaction (PCR) at the very least. When warranted, eradication treatment should be given when good compliance is expected, and there should be systematic use of a treatment adapted to the antimicrobial susceptibility profile. To combat the burgeoning threat of multidrug resistance, vigilant surveillance of resistance patterns and strategic antibiotic management are paramount.

Photochemical behavior of new sulfito complexes of cis-[Ru(phen)2(SO3)L]0/2-, where L = CO, H2O or SO32-

There is a need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. Recently, metal complexes have been recognized as promising sources for new antibiotics. In this context, Ru(II) complexes have shown good antimicrobial activity. Also, CO and SO32- ligands can exhibit interesting modulatory effects, since they show promising antibacterial properties. So, here, we synthesized and characterized three new compounds of the type cis-[Ru(phen)2(SO3)L]0/2-, where L = CO, H2O or SO32-. Their photochemical properties were also investigated, where we noticed that cis-[Ru(phen)2(SO3)(H2O)] complex did not show any photoreaction. However, cis-Na2[Ru(phen)2(SO3)2] and cis-[Ru(phen)2(SO3)(CO)], after light irradiation, release SO32- and CO, respectively, originating the same final photoproduct, cis-[Ru(phen)2(SO3)(H2O)]. At least three species with biological activities can emerge from the use of light: CO, SO32- and aqua ruthenium complex. Altogether, these results are encouraging and further biological studies might be explored.

Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development.

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

Molecular characterization and differential effects of levofloxacin and ciprofloxacin on the potential for developing quinolone resistance among clinical Pseudomonas aeruginosa isolates.

Fluoroquinolones are some of the most used antimicrobial agents for the treatment of Pseudomonas aeruginosa. This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among P. aeruginosa isolates at our medical center. 233 P. aeruginosa clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates. AST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 P. aeruginosa isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 μg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in gyrA, gyrB and parC genes. Understanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.

Anticipating resistance: Teaching gender and management to business school students

AbstractGender perspectives and feminism are rarely considered legitimate in business school education. Existing research tells us that those who teach in business schools do so in conditions where feminist theories and pedagogy evoke resistance and where their work is paved with discomfort caused by tensions between feminist and neoliberal idea(l)s. We argue that for those challenging the status quo in the business school through teaching, the impact of the threat of resistance can be as “real” as that of realized resistance. In this paper, we engage with collaborative autoethnography and elucidate how our anticipation of resistance shapes the way we teach, even when resistance does not materialize in the classroom. Building on reflections of our shared experiences, we theorize anticipated resistance as productive in and of itself, challenging the conventional view of resistance as brought into being through resisting practices at a specific time and place.