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Anthropogenic activities and climate change profoundly impact water quality, leading to a concerning increase in the prevalence and abundance of bacterial pathogens across diverse aquatic environments. This rise has resulted in a growing challenge concerning the safety of water sources, particularly surface waters and marine environments. This comprehensive review delves into the multifaceted challenges presented by bacterial pathogens, emphasizing threads to human health within ground and surface waters, including marine ecosystems. The exploration encompasses the intricate survival mechanisms employed by bacterial pathogens and the proliferation of antimicrobial resistance, largely driven by human-generated antibiotic contamination in aquatic systems. The review further addresses prevalent pathogenic bacteria, elucidating associated risk factors, exploring their eco-physiology, and discussing the production of potent toxins. The spectrum of detection techniques, ranging from conventional to cutting-edge molecular approaches, is thoroughly examined to underscore their significance in identifying and understanding waterborne bacterial pathogens. A critical aspect highlighted in this review is the imperative for real-time monitoring of biomarkers associated with waterborne bacterial pathogens. This monitoring serves as an early warning system, facilitating the swift implementation of action plans to preserve and protect global water resources. In conclusion, this comprehensive review provides fresh insights and perspectives, emphasizing the paramount importance of preserving the quality of aquatic resources to safeguard human health on a global scale. [Display omitted] • Pathogenic bacteria found in diverse aquatic systems were comprehensively reviewed. • Niche-specific sources, occurrence & survival tactics of pathogens were discussed. • Role of virulence factors of water-borne pathogens and their assessment was addressed. • Anthropogenic activity and antibiotic release drives water deterioration & AMR. • Future perspectives & challenges shaping the public health policies were discussed. [ABSTRACT FROM AUTHOR]

Antibiotic resistance (AR) is one of the major health threats of our time. The presence of antibiotics in the environment and their continuous release from sewage treatment plants, chemical manufacturing plants and animal husbandry, agriculture and aquaculture, result in constant selection pressure on microbial organisms. This presence leads to the emergence, mobilization, horizontal gene transfer and a selection of antibiotic resistance genes, resistant bacteria and mobile genetic elements. Under these circumstances, aquatic wildlife is impacted in all compartments, including freshwater organisms with partially impermeable microbiota. In this narrative review, recent advancements in terms of occurrence of antibiotics and antibiotic resistance genes in sewage treatment plant effluents source compared to freshwater have been examined, occurrence of antibiotic resistance in wildlife, as well as experiments on antibiotic exposure. Based on this current state of knowledge, we propose the hypothesis that freshwater aquatic wildlife may play a crucial role in the dissemination of antibiotic resistance within the environment. Specifically, we suggest that organisms with high bacterial density tissues, which are partially isolated from the external environment, such as fishes and amphibians, could potentially be reservoirs and amplifiers of antibiotic resistance in the environment, potentially favoring the increase of the abundance of antibiotic resistance genes and resistant bacteria. Potential avenues for further research (trophic transfer, innovative exposure experiment) and action (biodiversity eco-engineering) are finally proposed. [Display omitted] • Constant low concentrations of antibiotics and ARGs are measured in freshwater. • Antibiotics and ARGs concentration higher in effluent wastewater than freshwater. • Aquatic wildlife is reservoir/vector for dissemination of antibiotic resistance. • Aquatic wildlife microbiota are potential amplifiers of antibiotic resistance. • Trophic transfer experiment and biodiversity as research perspectives are proposed. [ABSTRACT FROM AUTHOR]

• This article presents the most recent data (2018) on the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France, alongside the control measures implemented in hospitals, from two complementary sources: external nosocomial infection notifications and the National Reference Centre for antibiotic resistance. This report shows the constant increase in the annual number of eXDR bacteria identified in France since 2012. This 2018 report of Healthcare-Associated Infections Early Warning and Response System (HAI-EWRS) notifications of carbapenemase-producing Enterobacteriaceae (CPE) or glycopeptide-resistant Enterococcus faecium (GRE), and of strains analysed by the National Reference Center for anti-microbial resistance (NRC) aimed to describe the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France and control measures implemented in hospital settings. All HAI-EWRS notifications of eXDR received at the national level and all eXDR strains received at the NRC between January 1, 2018 and January 31, 2018 were analysed. Variables analysed were number of cases, number of strains, resistance mechanism, sample type, link with a foreign country, and control measures implemented. In 2018, 1704 CPE notifications and 315 GRE notifications were reported in France, with an increasing trend since 2012 (× 6 for CPE, × 3 for GRE), from respectively 364 and 155 hospitals (+66% for CPE, +57% for GRE since 2012). eXDR strains were mainly isolated from rectal screening swabs. Notifications with patients receiving standard precautions were more often associated with outbreaks than notifications with patients receiving contact precautions at admission. NRC received 2674 CPE strains and 775 GRE strains in 2018 (× 8.3 and × 2.8 compared with 2012). The increasing annual number of eXDR notifications and eXDR strains received by the NRC is multifactorial but reflects a worrying spread of eXDR in France. The number of infections remains low, but this article shows that existing recommendations are not fully implemented. [ABSTRACT FROM AUTHOR]

Introduction: Primary breast abscesses occur in <1% of non-lactating women, rising to 11% in women with lactational mastitis. In patients undergoing breast cancer surgery, the inflammatory response to post-operative surgical site infection (SSI) has been implicated in recurrence. Anti-microbial resistance increasingly hampers treatment in each group.Aims: Describe the demographic and predisposing characteristics of patients with primary breast abscesses and secondary infections, identify the microbial and antimicrobial patterns and formulate an evidence-based protocol for treating breast infections.Methods: Retrospective cohort study of all breast infections (primary and post-operative) treated at UHL from 2014 to 2017. Data collected from microbiology databases and patient records was analysed using Minitab V18.Results: 537 cultures from 108 patients were analysed. 47 (43.5%) had primary abscesses, 12 (11.1%) were lactational and 49 (45.4%) were post-operative SSI. For primary infections, the mean age was 41.9 (±12.2) and reinfection rate 33%. For SSIs the mean age was 51.8 (±14.52) and reinfection rate 11.8%. Overall, 29.3% were smokers, 6.4% diabetic and 2.9% pregnant. 60 (43%) patients required radiological drainage and 2 (1%) surgical drainage. 57.5% had mixed growth. The most common isolate was Staphylococcus aureus; cultured in 16.7% of primary abscesses and 24% of SSIs. 13 empiric antibiotic regimes were prescribed before 26.4% of patients changed to 12 different targeted regimes.Conclusion: Breast infections are frequently polymicrobial with a wide variety of organisms isolated, suggesting the need for broad spectrum coverage until culture results become available. Based on our local culture results, the addition of clindamycin to flucloxacillin would provide excellent empiric coverage for all categories of breast infection. An evidence-based treatment guideline is required and should be formulated in close collaboration with microbiology specialists. [ABSTRACT FROM AUTHOR]

Objective CSE-1034 is a novel antibiotic adjuvant entity (AAE) with proven activity against broad range of multi-drug resistant (MDR) pathogens causing various bacterial infections. This phase 3 clinical trial was designed to evaluate the efficacy and safety of CSE-1034 therapy for the treatment of community-acquired pneumonia (CAP) patients of Pneumonia Outcomes Research Team (PORT) risk III–IV. Methods In this multi-centric, controlled, open-labeled phase 3 trial, adult patients with PORT risk III–IV CAP were randomized to receive either intravenous CSE-1034 (3 g every 12 h) or Ceftriaxone (2 g every 12 h) for 3–10 days. The primary endpoint was clinical response in clinically-evaluable (CE) population and microbiological eradication in microbiologically-evaluable (ME) population at test of cure (TOC) visits. Secondary endpoints included verification of the primary endpoints across all other visits, treatment duration and safety of patients. Results 156 patients were screened at 5 study centers of which 93 subjects were enrolled in the study and randomized in CSE-1034 and Ceftriaxone treatment arms. In CE population (n = 90), the clinical cure rates at TOC visit were 96% and 64% in CSE-1034 (n = 46) and Ceftriaxone (n = 44) treatment arms respectively (treatment difference: 32.0%; 95% CI, 15.8%–47.1%). The bacterial eradication in ME population of two treatment arms were 94% (n = 36) and 56% (n = 27) at TOC visit (treatment difference: 38.9%; 95% CI, 17.8%–57.6%). Overall, the total number of adverse events (AEs) reported in both groups were 21 (22.5%). The AEs rates reported in two treatment arms were 15.2% in CSE-1034 and 29.8% in Ceftriaxone group. Conclusion Overall assessment of clinical cure rate, microbiological eradication rate and safety assessment in this study has shown that CSE-1034 is an effective and safe option for the treatment of CAP patients of PORT risk III–IV. Moreover, the superiority of CSE-1034 over Ceftriaxone is also proven. [ABSTRACT FROM AUTHOR]

We investigate a drug target screening pipeline comparing sequence, structure and network-based criteria for prioritization. Serratia marcescens , an opportunistic pathogen, serves as test case. We rank according to (i) availability of three dimensional structures and lead compounds, (ii) not occurring in man and general sequence conservation information, and (iii) network information on the importance of the protein (conserved protein-protein interactions; metabolism; reported to be an essential gene in other organisms). We identify 45 potential anti-microbial drug targets in S. marcescens with KdsA involved in LPS biosynthesis as top candidate drug target. LpxC and FlgB are further top-ranked targets identified by interactome analysis not suggested before for S. marcescens . Pipeline, targets and complementarity of the three approaches are evaluated by available experimental data and genetic evidence and against other antibiotic screening pipelines. This supports reliable drug target identification and prioritization for infectious agents (bacteria, parasites, fungi) by these bundled complementary criteria. [ABSTRACT FROM AUTHOR]

Abstract: The presence of anti-microbial-resistant bacteria in the aquatic environment remains a matter of concern for environmental, animal and human health risks. Many published data have reported increased anti-microbial resistance among the aquatic microbiota from fish farm environments which often coincides with the use of anti-microbial agents. It can be assumed that the selection of anti-microbial-resistant bacteria first occurs in the fish farms themselves, at locations where anti-microbial concentrations are active. As anti-microbial agents are frequently administered through feed pellets, faecal matter excreted could favour conditions for such selection. In this study, OA (oxolinic acid) concentrations and OA resistance of Aeromonads were surveyed in output water and in faecal matter from OA medicated (test) and non-medicated (control) fish tanks during and after an OA oral treatment. Because of the low counts of Aeromonads in the output water, it was not possible to obtain reliable data on the proportion of anti-microbial resistance in this compartment. On the other hand, a time-limited effect on the abundance of Aeromonads isolated from faecal matter was only observed in test tanks. In these tanks, high proportion (80–100%) of OA-resistant Aeromonads was present in deposited faecal matter until at least one week after the end of the anti-microbial treatment. At that time OA was no longer detected within the faecal matter, after having reached concentrations between 100 and 190 μg/g during the treatment. We discuss how the leaching of OA from faecal pellets, from the intestine to their deposit, may favour the selection of OA-resistant Aeromonads. Further investigations in real conditions on microbiota associated with faecal matter in transit through the fish farm system are required. Particular attention should be paid to the wastes collected by the filter treatments of fish farm effluents. [Copyright &y& Elsevier]

Summary: Objective: The resurgence of tuberculosis (TB) and the emergence of drug resistance of Mycobacterium tuberculosis (MTB) isolates are of great impact on public health. Methods: Taiwanese data on disease burden of TB and anti-microbial resistance of MTB identified from Annual Reports of Centre for Disease Control, Department of Health, Taiwan and from peer-reviewed publications from MEDLINE (1995–2004). Results: In Taiwan in 2002, the incidence (per 100 000 population) of tuberculosis was 74.6 and it was higher in aborigines (289.8) and in people living in mountainous regions (256.0). The mortality rate of tuberculosis in Taiwan in 2002 was 5.68 per 100 000 population. Susceptibility data summarized from 1990 to 2002 reports showed primary resistance ranged from 4.7 to 12% for isoniazid, 0.7 to 5.9% for rifampin, 1 to 6% for ethambutol, and 4 to 11% for streptomycin. The overall rates of multidrug-resistant tuberculosis (MDRTB) among new cases and previously treated cases were 1 to 3% and 15 to 46%, respectively. The increasing burden of patients with MDRTB infection, the persistent high rate of mortality, the lack of nationwide surveillance system using the standard methodology to determine the trends and current status of resistance, and the inadequate current TB control infrastructure and training to accomplish the tasks required to implement the directly observed treatment short-course (DOTS) strategy are having a great impact on public health in Taiwan. Conclusions: High disease burden of TB and high resistance rates in MTB as well as inappropriateness of the current control infrastructure for TB services illustrate increasingly serious health problems from TB in Taiwan. [Copyright &y& Elsevier]

The EC Quality of Life (QoL) Programme, Key Action 1 (KA1)—Food, Nutrition and Health is mission oriented and aims, amongst other things, at providing a healthy, safe and high-quality food supply leading to reinforced consumer confidence in the safety of European food. Its objectives also include the enhancing of competitiveness of European industry and ensuring the safety of the European food supply. Key Action 1 is currently supporting a number of different types of European collaborative projects in the area of anti-microbial and hormone residue analysis. The objectives of these projects range from the development and validation of screening and confirmatory analytical methods and sensors for a cost-effective and time efficient control strategy for synthetic glucocorticoids, nitrofurans including their possible bound residues, coccidiostatics, β-lactam residues, and androgen residues in live and post-mortem animals; via contributing to a harmonisation of risk assessment of chemicals in foods; and a bio-safety evaluation of probiotic lactic acid bacteria (LAB) used for human consumption in order to detect resistance and horizontal transfer of antibiotic resistance genes among LAB. An overview of these projects including their initial results is presented in this paper. [Copyright &y& Elsevier]

Streptococcus pneumoniae and Streptococcus pyogenes are common agents of respiratory or ORL pathology. Pneumococcus sensitivity has progressively decreased to penicillin and other antimicrobial agents, mainly in south of Europe, but this resistance report can be erroneous by a selection bias, because they sampled only hospital cases. Objectives: To determine the prevalence, antimicrobial susceptibility and risk factors of S. pneumoniae and S. pyogenes in healthy children under 5 years of age who go to infant school. Subject and Methods: Cross sectional study in six infant schools. An epidemiological inquiry (risk factors of carrier state) was filled out and a nasopharyngeal specimen was taken from each child, S. pneumoniae and S. pyogenes were identified and antimicrobial tests were performed. Results: We have studied 156 children with a mean age of 2.24 (standard deviation (S.D.), 0.85) and 58% have been treated with antibiotic in the last 3 months. The prevalence of S. pneumoniae or S. pyogenes were 12.2 and 5.1%, respectively. S. pyogenes only was isolated in two schools. Age was associated with S. pyogenes carrier but the rest of studied factors have no statistical significance with both microorganisms. All the S. pneumoniae showed resistance to one or more antibiotic (mainly to clavunate-amoxycillin: 94.7%), while S. pyogenes only was resistant to clavunate-amoxycillin. Conclusion: Healthy children (0–4 years) with antibiotherapy in last 3 months have a great frequency of resistant S. pneumoniae. It is necessary to reduce the antibiotic use at home (Medical education). [Copyright &y& Elsevier]

Nanostructured lipid-based carriers (NLCs) efficiently improved as potential targeted drug delivery for six common pathogens eradication. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) showed that all the formulas fully characterized nanosize and surface-negative charge and presented the drug's slow release even after 48 h in vitro. The biological studies proved that the nanostructures' antibacterial potency is in the order of Fe 3 O 4

Many critical dilemmas currently face global authorities in TB control. This article highlights one of the most challenging which is drug-resistance. MDR-TB is estimated to account for at least one third of all deaths associated with anti-microbial resistance, but remains largely undiagnosed and untreated, particularly in countries with inadequate health infrastructures which also have a high prevalence of latent infection. This article considers the growing primary evidence that a Traditional Japanese Moxibustion (TJM) technique with known immunomodulatory effects may help significantly improve treatment outcomes with MDR-TB. Data from three recent primary research programs in resource-limited environments (in Uganda and the DPRK) are discussed and evaluated in terms of outcomes, as well as in respect of the therapy's low-cost and low-tech nature. These data suggest that the therapy may be helpful in developing countries in reducing infectivity in TB cases (including those co-infected with HIV) as well as in accelerating recoveries, and significantly enhancing recoveries in MDR-TB cases. They also suggest that TJM may also prevent the emergence of MDR-TB from latent infection. There is an urgent need for better understanding of these effects. A model for further investigation of moxa treatment for MDR-TB is presented. This could generate further data that might be used by WHO and Member States, potentially enabling them to integrate TJM into their TB treatment programmes, thereby benefitting large numbers of vulnerable patients at very little extra cost. [ABSTRACT FROM AUTHOR]

• Multiple hotspot sources emit antibiotic resistance genes (ARGs) into wastewaters. • Wastewater treatment processes contribute to the persistence and fate of ARGs. • Vectors, contaminated water and food transfer ARGs from wastewater to humans. • Complex human-environmental interactions control the behaviour and fate of ARGs. • Risks assessments should include interaction of ARGs and environmental stressors. Limited reviews have investigated sources, behaviour and health risks of antimicrobial resistance genes (ARGs) in the wastewater-human pathway. The current review seeks to: (1) determine hotspot sources of ARGs, and their behaviour and fate in wastewaters; (2) discuss ARG health risks, and risk factors; and (3) highlight future research directions. Diverse ARGs conferring single and multi-drug resistance to common and last-resort antimicrobials are widely reported. Hotspot sources of ARGs include medical facilities, pharmaceutical industries, aquaculture and animal systems. Non-engineered landfills, on-site sanitation, funeral parlours and gravesites constitute under-studied potential hotspot sources. Hydrological processes, wind and vectors mobilize ARGs from sources into aquatic systems. Wastewater treatment processes, the nature of ARGs and environmental conditions control the behaviour and fate of ARGs. Consumption of contaminated food and water, vectors, inhalation and dermal contact transfer ARGs from wastewaters to humans. Health risks include development of antimicrobial resistance, although evidence directly linking ARGs in wastewater to resistance remains weak. Ecological risks include shifts in physiological behaviour, community structure and ecosystem functions, including expression of shock-responses and virulence, biofilm formation and mutations. These shifts could increase colonization ability and survival of pathogenic microbes, thereby posing significant ecological, human and animal health risks. Overall, the behaviour and risks of ARGs are controlled by complex human-environmental interactions, and have far-reaching policy implications, hence ARGs can be considered as a 'super-wicked' problem. To minimize the risks, a conceptual framework entailing a ten-point strategy is highlighted. Under-studied hotspot sources, behaviour and fate, human ecotoxicology and risk assessments warrant further research. [ABSTRACT FROM AUTHOR]