Risk Of Antimicrobial Resistance Research Articles

Investigating the Antimicrobial Potential of 560 Compounds from the Pandemic Response Box and COVID Box against Resistant Gram-Negative Bacteria.

Antimicrobial resistance (AMR) has emerged as a significant threat to public health, particularly in infections caused by critically important Gram-negative bacteria. The development of novel antibiotics has its limitations, and therefore it is crucial to explore alternative strategies to effectively combat infections with resistant pathogens. In this context, the present study investigated the antibacterial potency of 560 compounds against the multidrug-resistant (MDR) strains of Klebsiella pneumoniae and Serratia marcescens. The evaluated compounds were selected from the Pandemic Response Box (PRB) and COVID Box (CB) and subjected to assays to determine the inhibitory concentration (IC), minimum bactericidal concentration (MBC), and biofilm formation. Further, the effects of these compounds on membrane integrity were assessed through protein quantification. Several of the evaluated compounds, including fusidic acid, MMV1580853, and MMV1634399, exhibited a significant reduction in biofilm formation and growth in K. pneumoniae. Trimethoprim exhibited potential against S. marcescens. The IC values of the compounds indicated significant microbial growth inhibition at various concentrations. These findings underscore the potency of the existing antibiotics and novel compounds in combating the MDR strains of bacteria. The importance of reconsidering the known antibiotics and utilizing drug repositioning strategies to address the increasing risk of AMR is highlighted.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption

BackgroundTuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. ObjectivesThis study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. MethodsA multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. ResultsOf 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0–2), medium (3–5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). ConclusionThe predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Healthcare as a driver, reservoir and amplifier of antimicrobial resistance: opportunities for interventions.

Antimicrobial resistance (AMR) is a global health challenge that threatens humans, animals and the environment. Evidence is emerging for a role of healthcare infrastructure, environments and patient pathways in promoting and maintaining AMR via direct and indirect mechanisms. Advances in vaccination and monoclonal antibody therapies together with integrated surveillance, rapid diagnostics, targeted antimicrobial therapy and infection control measures offer opportunities to address healthcare-associated AMR risks more effectively. Additionally, innovations in artificial intelligence, data linkage and intelligent systems can be used to better predict and reduce AMR and improve healthcare resilience. In this Review, we examine the mechanisms by which healthcare functions as a driver, reservoir and amplifier of AMR, contextualized within a One Health framework. We also explore the opportunities and innovative solutions that can be used to combat AMR throughout the patient journey. We provide a perspective on the current evidence for the effectiveness of interventions designed to mitigate healthcare-associated AMR and promote healthcare resilience within high-income and resource-limited settings, as well as the challenges associated with their implementation.

UNNECESSARY USE OF ANTIMICROBIALS – COMPARISON OF THE PREDICTIVE PERFORMANCE OF QSOFA AND APACHE SCORE FOR EVALUATION OF DISEASE PROGNOSIS PATTERNS IN CRITICAL ILLNESS

In critical care, accurate prognosis assessment, including antimicrobial therapy, is vital for guiding treatment decisions. The Acute Physiology and Chronic Health Evaluation (APACHE) and quick Sequential Organ Failure Assessment (qSOFA) scores are widely used for predicting patient outcomes. Yet, their relative performance and potential implications for antimicrobial stewardship need further exploration. Objective: To evaluate the disease prognosis patterns in critically ill patients by comparing the predictive performance of APACHE and qSOFA scores and to explore their correlation with antimicrobial misuse. Methods: A comparative study was conducted at the National Hospital and Medical Center in Lahore from January to November 2023. The study included 138 critically ill patients. Demographic information, clinical parameters, and medical history were collected, explicitly focusing on APACHE and qSOFA scores recorded at admission and during follow-up. Statistical analysis, including Pearson's and Spearman's correlation coefficients and logistic regression models, was performed using RStudio to assess the predictive ability of these scores for disease progression and patient outcomes. Results: The analysis revealed a moderate positive correlation (r=0.51) between qSOFA and APACHE-II scores, suggesting that both scores align in assessing the severity of illness in critically ill patients. The predictive models indicated that combining qSOFA and APACHE-II scores enhanced the accuracy of predicting critical outcomes, such as shortness of breath (SOB), with a combined model AUC of 0.659 compared to 0.601 for the APACHE-II model alone. Conclusion: The findings underscore the value of integrating multiple clinical scoring systems in managing critically ill patients. Such integration can aid in more judicious use of antibiotics, potentially mitigating the risk of antimicrobial resistance. The study advocates incorporating these insights into clinical guidelines and decision-making processes in critical care settings.

An Analysis of the Cost Variation Among Different Antimicrobial Agents: The Indian Scenario.

Background and objective Infectious diseases pose a substantial global health challenge, especially in developing countries where healthcare accessibility is limited. Pharmaceutical expenses constitute a significant share of out-of-pocket expenditure (60-90%). Hence, the affordability of medications becomes a critical determinant for patient compliance. This study focuses on the economic dynamics of antimicrobial agents. Methodology After collecting data from the Current Index of Medical Specialties (CIMS), different antimicrobial agents (AMAs) were assessed based on their cost per 10 tablets/10 capsules/one vial of injection. A comprehensive analysis was performed to assessthe minimum and maximum costs for each medication across diverse pharmaceutical companies. Cost variation was assessed through both the cost ratio and percentage cost variation.The data were analyzed and represented using descriptive statistics Results Our findings indicate significant cost variations, with nitrofurantoin 100 mg tabletshowcasing a staggering 1498.5% variation, followed by meropenem 500 mg vial at 473.91%. Conversely, the cotrimoxazole (sulfamethoxazole 800 mg + trimethoprim 160 mg) tablet exhibits a minimal 6.05% variation, underscoring the diversity in pricing strategies. The number of brands ranged from two to 62. Conclusions This study underscores the importance of considering cost variations in antimicrobial agents while prescribing the same. Doing so will not only address the economic challenges faced by patients but also help in improvingcompliance and reducing the risk of antimicrobial drug resistance. This approach advocates for a more economically sustainable and patient-centric healthcare ecosystem in India.

Guidelines to practice in hospitals at home: safe and effective continuous infusion pumps substantially increased penicillin use in erysipelas treatment.

Hospitals at home are increasingly offering outpatient parenteral antimicrobial therapy (OPAT) in an attempt to reduce costly inpatient care, but these settings favour broad-spectrum antibiotics that require less frequent dosing than penicillin. Benzyl penicillin could be delivered via continuous infusion pumps (eCIPs), but studies on their safety and efficacy in OPAT are scarce, and it remains unclear how much the availability of eCIPs increases penicillin use in real-life settings. We examined 462 electronic healthcare records of erysipelas patients treated between January 2018 and January 2022 in a large Finnish OPAT clinic. Average marginal effects from logistic models were estimated to assess how the introduction of eCIPs in December 2020 affected penicillin use and to compare clinical outcomes between patients with and without eCIPs. Introduction of eCIPs increased the predicted probability of penicillin treatment by 36.0 percentage points (95% confidence interval 25.5-46.5). During eCIP implementation, patients who received an eCIP had 73.1 (58.0-88.2) percentage points higher probability than patients without an eCIP to receive penicillin treatment. They also had about 20 percentage points higher probability to be cured at the time of discharge and 3 months after it. Patient and nurse satisfaction regarding eCIPs was very high. Benzyl penicillin eCIP treatment is effective and safe, and substantially increases the use of penicillin instead of broad-spectrum antibiotics. To reduce the risk of antimicrobial resistance, eCIPs could increasingly be promoted for use in OPAT clinics, and there should be adequate education and support in their implementation.

Antibiotics removal and antimicrobial resistance control by ozone/peroxymonosulfate-biological activated carbon: A novel treatment process

Biological activated carbon (BAC) is one of the important treatment processes in wastewater and advanced water treatment. However, the BAC process has been reported to have antimicrobial resistance (AMR) risks. In this study, a new BAC-related treatment process was developed to reduce AMR caused by BAC treatment: ozone/peroxymonosulfate-BAC (O3/PMS-BAC). The O3/PMS-BAC showed better treatment performance on the targeted five antibiotics and dissolved organic matter removal than O3-BAC and BAC treatments. The O3/PMS-BAC process had better control over the AMR than the O3-BAC and BAC processes. Specifically, the amount of targeted antibiotic-resistant bacteria in the effluent and biofilm of O3/PMS-BAC was only 0.01–0.03 and 0.11–0.26 times that of the BAC process, respectively. Additionally, the O3/PMS-BAC process removed 1.76 %–62.83 % and 38.14 %–99.27 % more of the targeted ARGs in the effluent and biofilm than the BAC process. The total relative abundance of the targeted 12 ARGs in the O3/PMS-BAC effluent was decreased by 86 % compared to the effluent after BAC treatment. In addition, Proteobacteria and Bacteroidetes were probably the main hosts for transmitting ARGs in this study, and their relative abundance decreased by 9.6 % and 6.0 % in the effluent of the O3/PMS-BAC treatment compared to that in BAC treatment. The relationship analysis revealed that controlling antibiotic discharge was crucial for managing AMR, as antibiotics were closely related to both ARGs and bacteria associated with their emergence. The results showed that the newly developed treatment process could reduce AMR caused by BAC treatment while ensuring effluent quality. Therefore, O3/PMS-BAC is a promising alternative to BAC treatment for future applications.

Key aspects of biosafety in modern animal husbandry

The relevance of this research is driven by the need to enhance biosecurity in animal husbandry to improve the health and productivity of livestock, as well as to safeguard human health. Biosecurity is a critical component that prevents the spread of infectious diseases, mitigates the risks of epidemics, reduces treatment costs, and increases productivity and economic efficiency within agricultural enterprises. In this regard, this study aimed to reveal the role of biosafety in preventive veterinary medicine. The leading approach to investigating this issue involved analysing existing practices and methods, which allows for a comprehensive examination of various aspects of biosecurity. The conducted analysis substantiated that preventive veterinary medicine is founded on the principle of disease prevention through risk reduction and the implementation of healthy practices. It has been established that this approach encompasses not only the treatment of sick animals but also the provision of advice to farmers on enhancing the health and productivity of their livestock. It has been established that biosecurity also helps prevent the emergence and spread of infectious diseases, reducing the need for antimicrobial drugs and lowering the risk of antimicrobial resistance. The research highlighted that in today’s rapidly changing world, biosecurity is becoming even more important due to population growth, urbanisation, climate change, and human health threats such as antimicrobial resistance. The concept of “One Health” is encompassed, emphasising the close connection and interdependence among the health of humans, domestic and wild animals, plants, and the environment. The core principles of biosecurity included segregation, cleaning and disinfection, and considering the behaviour and attitudes of people working with animals. The material presented in this article is of practical value to veterinarians, farmers, and livestock farms, assisting them in developing and implementing effective biosecurity plans adapted to changing conditions, thereby contributing to reducing the risks of infectious diseases and improving livestock productivity

Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

Microbiologic Evaluation of Colorectal Surgical Site Infections to Guide Surgical Prophylaxis Recommendations

Background: Use of a combination of parenteral and oral antimicrobial prophylaxis prior to colorectal surgery is recommended to reduce risk of surgical site infection (SSI). Parenteral antibiotic selection is complicated by the need to target organisms likely to cause infection at the surgery site, while mitigating risk of antimicrobial resistance caused by overuse of broad spectrum agents. This study aimed to evaluate microbiologic data from colorectal surgical site infections across an 11-hospital health system. Microbiologic data from SSI events were used to assess continued appropriateness of health system standard recommendations for parenteral antibiotic prophylaxis in colorectal surgery, consisting of either cefazolin with metronidazole or cefoxitin monotherapy. Methods: This multicenter, retrospective, observational study was conducted from January 1, 2019 to March 31, 2023, using data extracted from the National Healthcare Safety Network (NHSN). Microbiologic data from colorectal SSIs from 2019 to 2022 were evaluated for a descriptive review of pathogen and phenotype trends. SSI data excluded patients age &lt; 18 years, those identified as infection present at time of surgery (PATOS), or outpatient procedures. Results: A total of 8059 colorectal procedures were evaluated. Most SSIs were polymicrobial, with at least one pathogen detected in 65% of cases. The most commonly identified organisms were E. coli (22.5%), Enterococcus spp. (19.7%), P. aeruginosa (6.5%), Streptococcus spp. (4.9%), and C. albicans (4.7%). Change over time in antimicrobial-resistant phenotypes from 2019 to 2022 was not statistically significant for extended-spectrum cephalosporin-resistant E. coli (p=0.335), extended-spectrum cephalosporin-resistant K. oxytoca/pneumoniae (p=0.189), multi-drug resistant P. aeruginosa (0.058), methicillin-resistant S. aureus (p=0.906), or among isolates with no identified antimicrobial-resistance phenotype (p=0.096). Among E. coli, change from 2019 to 2022 in cefazolin non-susceptible, ceftriaxone susceptible isolates was not statistically significant (p=0.177). No carbapenem-resistant Enterobacterales isolates were identified among non-PATOS cases. Conclusions: Data does not support a change to broader spectrum agents for colorectal surgery parenteral antimicrobial prophylaxis. Continued use of cefazolin with metronidazole or cefoxitin as IV antibiotic prophylaxis in colorectal surgery is recommended, with ongoing tracking of microbiologic trends and antimicrobial susceptibility.

Individual health insurance data of antibiotic delivery in previous months as a tool to predict bacterial resistance of urinary tract infection: A prospective cohort study

ObjectivesWe aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months. Patients and methodsFrench patients were prospectively recruited in two centers in 2015–2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files. ResultsPrevious antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20–2.21], 1.59 [1.02–2.48], 3.01 [1.90–4.77], and 2.60 [1.75–3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41–1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]). ConclusionsResistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

Sow reproductive performance following artificial insemination with semen doses processed using Single Layer Centrifugation without antibiotics in the tropics

Single Layer Centrifugation (SLC) through a low density colloid offers an alternative solution to antibiotic use in boar semen extenders, with lower costs compared to high density colloids. The aim of this study was to explore the reproductive performance of sows when using SLC-prepared semen doses without antibiotics, employing low density Porcicoll to prepare semen doses for artificial insemination in a commercial swine herd in Thailand. Ejaculates were divided into two equal parts to create insemination doses, with each dose containing 3000 × 106 sperm/80 ml for intra-uterine insemination in individual sows. The sows were inseminated twice, with the interval between the two inseminations ranging from 8 to 16 h. The CONTROL group consisted of 206 semen doses treated with antibiotics, prepared for insemination in 103 sows, while the SLC group comprised 194 SLC-prepared semen doses without antibiotics for inseminating 97 sows. Fertility and fecundity traits, including non-return rate, conception rate, farrowing rate, and litter traits (i.e., the total number of piglets born per litter, number of piglets born alive per litter, number of stillborn piglets, and number of mummified fetuses), were compared between groups. Furthermore, data on piglet characteristics, including live-born and stillborn piglets (i.e., the prevalence of stillbirth (yes, no), birth weight, crown-rump length, body mass index (BMI), and ponderal index (PI)), were determined. No significant differences in non-return rate (75.7 % vs. 77.3 %), conception rate (73.8 % vs. 73.2 %), and farrowing rate (71.8 % vs. 73.2 %) were observed between the CONTROL and SLC groups, respectively (P > 0.05). Nevertheless, the total number of piglets born per litter in the SLC group was higher than in the CONTROL group (14.6 ± 0.9 vs. 12.3 ± 0.6, respectively, P = 0.049). Interestingly, the prevalence of stillbirth in the SLC group was lower than in the CONTROL group (6.2 % vs. 11.6 %, respectively, P < 0.001). Moreover, the newborn piglets in the SLC group exhibited higher birth weight and BMI compared to those in the CONTROL group (1.36 ± 0.03 vs. 1.26 ± 0.02 kg, P = 0.005, and 18.3 ± 0.3 vs. 17.3 ± 0.2 kg/m2, P = 0.003). In conclusion, employing sperm doses after SLC through a low density colloid in artificial insemination within a commercial breeding operation did not have a detrimental impact on either fertility or fecundity traits but showed potential benefits in increasing the total number of piglets born per litter. Moreover, improvements were observed in the birth weight and body indexes of piglets, and the percentage of stillbirths was reduced. Our findings introduce new possibilities for antibiotic alternatives in semen extenders to reduce the risk of antimicrobial resistance in the swine industry. Additionally, they provide compelling reproductive outcomes supporting the integration of SLC-prepared semen doses into artificial insemination practices.

Key environmental exposure pathways to antimicrobial resistant bacteria in southern Malawi: A SaniPath approach

Antimicrobial resistance (AMR) poses a severe global health threat, yet the transmission pathways of AMR within communal public environments, where humans and animals interact, remain poorly explored. This study investigated AMR risk pathways, prevalence, and seasonality of extended-spectrum β-lactamase (ESBL) producing E. coli and K. pneumoniae, and observed practices contributing to environmental contamination within urban, peri-urban, and rural Malawi.Using the SaniPath tool, in August 2020, transect walks across three Malawian study sites identified potential AMR exposure pathways, including drains, standing water, soil, and areas of communal hand contact. Subsequently, from September-2020 to August-2021, 1440 environmental samples were collected at critical points along exposure routes (n = 40/month from each site). These underwent microbiological analysis using chromogenic agar techniques to detect the presence of ESBL E. coli and ESBL K. pneumoniae.Results showed the highest ESBL prevalence in urban environments (68.1 %, 95%CI = 0.64–0.72, p < 0.001) with a higher ESBL presence seen in drains (58.8 %, 95%CI = 055–0.62, p < 0.001) and soil (54.1 %, 95%CI = 0.46–0.62, p < 0.001) compared to other pathways. Environmental contamination was attributed to unavailability and poor condition of sanitation and hygiene infrastructure based on key informant interviews with community leaders (n = 9) and confirmed by independent observation. ESBL prevalence varied between seasons (χ2 (2,N = 1440) = 10.89, p = 0.004), with the highest in the hot-dry period (55.8 % (n = 201)). Prevalence also increased with increased rainfall (for ESBL E.coli).We highlight that community environments are likely to be a crucial component in AMR transmission, evident in the abundance of ESBL bacteria in identified exposure pathways. Additionally, poor sanitation infrastructure and practices coupled with seasonal dynamics further affect the presence of ESBLs in communal environments. Therefore, a context appropriate whole system approach that tackles infrastructure and behavioural factors, supported by effective surveillance is required to impact AMR and a range of aligned development challenges in these settings.

‘Male cystitis does not exist’: A qualitative study of general practitioners’ experiences and management of male urinary tract infections in France

Background Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance. Objectives The objective of this qualitative study was to explore general practitioners’ (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs. Methods GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs’ experiences and behaviours were recorded and analysed using an interpretive phenomenological approach. Results From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: ‘male cystitis does not exist’. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be ‘potent’ antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system. Conclusions GPs’ experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs’ antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed. KEY MESSAGES Defining a male urinary tract infection represents a diagnostic challenge for GPs. A diagnosis based on clinical evidence alone is insufficient and complementary tests are required. A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.

Occurrence and Distribution of Antibacterial Quaternary Ammonium Compounds in Chinese Estuaries Revealed by Machine Learning-Assisted Mass Spectrometric Analysis.

Antimicrobial resistance (AMR) undermines the United Nations Sustainable Development Goals of good health and well-being. Antibiotics are known to exacerbate AMR, but nonantibiotic antimicrobials, such as quaternary ammonium compounds (QACs), are now emerging as another significant driver of AMR. However, assessing the AMR risks of QACs in complex environmental matrices remains challenging due to the ambiguity in their chemical structures and antibacterial activity. By machine learning prediction and high-resolution mass spectrometric analysis, a list of antibacterial QACs (n = 856) from industrial chemical inventories is compiled, and it leads to the identification of 50 structurally diverse antibacterial QACs in sediments, including traditional hydrocarbon-based compounds and new subclasses that bear additional functional groups, such as choline, ester, betaine, aryl ether, and pyridine. Urban wastewater, aquaculture, and hospital discharges are the main factors influencing QAC distribution patterns in estuarine sediments. Toxic unit calculations and metagenomic analysis revealed that these QACs can influence antibiotic resistance genes (particularly sulfonamide resistance genes) through cross- and coresistances. The potential to influence the AMR is related to their environmental persistence. These results suggest that controlling the source, preventing the co-use of QACs and sulfonamides, and prioritizing control of highly persistent molecules will lead to global stewardship and sustainable use of QACs.

Neglected risks of enhanced antimicrobial resistance and pathogenicity in anaerobic digestion during transition from thermophilic to mesophilic

Minimization of antibiotic resistance genes (ARGs) and potential pathogenic antibiotic-resistant bacteria (PARB) during anaerobic digestion (AD) is significantly impacted by temperature. However, knowledge on how ARGs and PARB respond to temperature transition from thermophilic to mesophilic is limited. Here, we combined metagenomic-based with culture-based approaches and revealed the risks of antimicrobial resistance and pathogenicity during transition from 55 °C to 35 °C for AD, with strategies of sharp (ST, one-step by 20 °C/d) and mild (MT, step-wise by 1 °C/d). Results indicated a lower decrease in methane production with MT (by 38.9%) than ST (by 88.8%). Phenotypic assays characterized a significant propagation of multi-resistant lactose-fermenting Enterobacteriaceae and indicator pathogens after both transitions, especially via ST. Further genomic evidence indicated a significant increase of ARGs (29.4-fold), virulence factor genes (1.8-fold) and PARB (65.3-fold) after ST, while slight enrichment via MT. Bacterial succession and enhanced horizontal transfer mediated by mobile genetic elements promoted ARG propagation in AD during transition, which was synchronously exacerbated through horizontal transfer mechanisms mediated by cellular physiological responses (oxidative stress, membrane permeability, bacterial conjugation and transformation) and co-selection mechanisms of biomethanation metabolic functions (acidogenesis and acetogenesis). This study reveals temperature-dependent resistome and pathogenicity development in AD, facilitating microbial risk control.

Mechanisms linking triclocarban biotransformation to functional response and antimicrobial resistome evolution in wastewater treatment systems

Evaluating the role of antimicrobials biotransformation in the regulation of metabolic functions and antimicrobial resistance evolution in wastewater biotreatment systems is crucial to ensuring water security. However, the associated mechanisms remain poorly understood. Here, we investigate triclocarban (TCC, one of the typical antimicrobials) biotransformation mechanisms and the dynamic evolution of systemic function disturbance and antimicrobial resistance risk in a complex anaerobic hydrolytic acidification (HA)-anoxic (ANO)/oxic (O) process. We mined key functional genes involved in the TCC upstream (reductive dechlorination and amide bonds hydrolysis) and downstream (chloroanilines catabolism) biotransformation pathways by metagenomic sequencing. Acute and chronic stress of TCC inhibit the production of volatile fatty acids (VFAs), NH4+ assimilation, and nitrification. The biotransformation of TCC via a single pathway cannot effectively relieve the inhibition of metabolic functions (e.g., carbon and nitrogen transformation and cycling) and enrichment of antimicrobial resistance genes (ARGs). Importantly, the coexistence of TCC reductive dechlorination and hydrolysis pathways and subsequent ring-opening catabolism play a critical role for stabilization of systemic metabolic functions and partial control of antimicrobial resistance risk. This study provides new insights into the mechanisms linking TCC biotransformation to the dynamic evolution of systemic functions and risks, and highlights critical regulatory information for enhanced control of TCC risks in complex biotreatment systems.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis

ObjectiveTargeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in...

Why Assuring the Quality of Antimicrobials Is a Global Imperative.

Poor-quality antimicrobial medicines continue to proliferate across supply chains, threatening patients' health and safety, especially in low- and middle-income regions. This article discusses consequences and risks of antimicrobial resistance and other ways in which antimicrobial medicines can be of poor quality and recommends regulatory and policy reforms to help maintain supply chain resilience and quality of antimicrobial medicines.

Algorithm for the development of a multicomponent pharmaceutical substance of plant origin with antimicrobial action: from science search to dosage form

Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.