Impact of residual antibiotics on microbial decomposition of livestock manures in Eutric Regosol: Implications for sustainable nutrient recycling and soil carbon sequestration.

The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%-87%), nitrogen (15%-44%) and phosphorus (26%-43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%-13% while fungi increased by 7.0%-71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, ß-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.

A Supramolecular Antibiotic Targeting Drug-Resistant Pseudomonas aeruginosa through the Inhibition of Virulence Factors and Activation of Acquired Immunity.

The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.

Clostridioides difficile Infection Risk Following Different Antibiotics: Insights from Multi-source Medical Data.

OBJECTIVE: Antibiotic utilization stands as the strongest modifiable determinant for Clostridioides difficile infection (CDI). However, previous studies have relied on aggregated antibiotic categories, leaving prescribers without detailed comparative risk information for individual antibiotics. Our objective was to comprehensively estimate CDI risks across specific antibiotics. METHODS: We integrated 2 methodologies to access and rank the CDI risk associated with individual antibiotics or classes. Initially, we conducted a network comparison by analyzing data from randomized controlled trials (RCTs). Subsequently, a real-world disproportionality analysis using the Food and Drug Adverse Event Reporting System (FAERS) database complemented and enriched the findings from RCTs. RESULTS: The network comparison, encompassing 61 RCTs with 25,931 patients, revealed that exposure to cefepime (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.20-5.44, P=0.02) and imipenem/cilastatin (OR 3.86, 95%CI 1.61-9.29, P=0.003) exhibited higher frequencies of CDI compared to piperacillin/tazobactam. No statistically significant distinctions emerged among carbapenems, albeit a trend indicating a heightened CDI incidence with imipenem/cilastatin relative to meropenem (OR 3.89, 95%CI 0.94-16.09). In the FAERS disproportionality analysis, nearly all antibiotics displayed associations with CDI, and CDI risk signals often cluster within the majority of antibiotic classes. Among these, lincomycin demonstrated the strongest association (reporting odds ratios 112.17, 95%CI 51.68-243.43). Additionally, oral third-generation cephalosporins tend to exhibit higher CDI risk signals than others. CONCLUSIONS: Our findings unveiled substantial diversity in CDI risk, both within and among antibiotic classes, providing valuable guidance for clinicians in antibiotic prescription decisions and for initiatives aimed at antibiotic stewardship.

Changing epidemiological trend of Aeromonas species and ciprofloxacin sensitivity in South India.

Aeromonas species can cause a wide range of clinical infections. Several reports of drug resistance among the Aeromonas species have been reported, but our observations have differed. Here we present the changing susceptibility pattern of antibiotics for Aeromonas species over 14 years (January 2010- February 2024) at a tertiary care hospital in South India.

Antibiotic Use in the Surgical Intensive Care Unit.

Judicious use of antibiotics in the critically ill starts with the evaluation for suspected infection, including close consideration of the patient's history. If infection is present or strongly suspected, empiric antibiotics should be promptly initiated and selected based on the source of infection, patient factors, and local resistance patterns. If the surgeon decides source control is indicated, they must determine the optimal approach and timing. As soon as culture and sensitivity data are available, de-escalation to narrower spectrum agents is essential to decrease the risks of antibiotic toxicity and resistance. Importantly, surgeons should participate in antibiotic stewardship in their patients.

Are Antibiotics of Value for a Whipple Procedure?

Pancreatoduodenectomy is a complex surgical procedure with a high rate of morbidity, of which surgical-site infections (SSIs) make a large portion. Reduction of SSI rates is critical to decrease hospital lengths of stay, readmissions, delays in adjuvant therapies, and financial health care burden. Current clinical guidelines recommend the administration of cefoxitin as surgical prophylaxis prior to pancreatoduodenectomy. In April 2023, a randomized controlled trial was published in JAMA which showed that piperacillin-tazobactam as perioperative surgical prophylaxis prior to pancreatoduodenectomy decreased 30 day SSI rates (primary outcome), clinically relevant postoperative pancreatic fistula, postoperative sepsis, and Clostridium difficile infection rates.

Current Management of Diverticulitis.

Over the last few decades, our understanding of the pathophysiology and natural history of sigmoid diverticulitis has greatly improved. This knowledge has challenged many of the traditional principles in the management for diverticulitis, such as routine antibiotic administration in all cases, number-based recommendations for elective surgery, and the necessity for an end colostomy in emergency surgery. This review will cover the breadth of management for sigmoid diverticulitis, covering both uncomplicated and complicated disease as well as elective and emergent disease presentations. New and emerging concepts in management will be highlighted with a particular focus on level-1 data, when available.

Influence of Kidney Environment Parameters on Antibiotic Efficacy Against Uropathogenic Escherichia coli.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common infections affecting the urinary system, predominantly caused by bacterial pathogens, with Escherichia coli being the most frequent pathogen. Infections of the kidney (eg, pyelonephritis) are severe and challenging to treat, due to the specific tissue microenvironment. In this study, the influence of different parameters mimicking the kidney environment on the effectiveness of antibiotics prescribed for pyelonephritis on the growth of uropathogenic strains was analyzed. METHODS: To investigate the influence of different factors mimicking the kidney environment, we tested the effect of different kidney-representative concentrations of sodium chloride and urea, and different pH values on the efficacy of ertapenem, levofloxacin, and ceftriaxone. The effectiveness was assessed by determining the minimal inhibitory concentrations (MICs) against various E. coli strains. KEY FINDINGS AND LIMITATIONS: The study revealed that pH significantly influences the MIC values of levofloxacin. Acidification of the pH led to an increase of the MIC values, while an alkaline pH had the opposite effect. The influence of sodium chloride and urea concentrations was strain and antibiotic specific. Since three different antibiotics were tested in this study, further research with additional antibiotics is warranted. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results suggest that the physicochemical conditions within the kidney can substantially influence the success of antibiotic therapy for pyelonephritis. Therefore, it is crucial for clinicians to consider these factors when selecting and dosing antibiotics. Further research is needed to evaluate a broader range of antibiotics and additional environmental parameters, to develop a more comprehensive understanding of how the kidney environment affects antimicrobial activity. This knowledge will be vital in optimizing treatment strategies for pyelonephritis, ultimately improving patient outcomes. PATIENT SUMMARY: The physicochemical conditions within the kidney influence the success of antibiotic therapy for pyelonephritis. Our findings are vital in optimizing treatment strategies and will ultimately improve patient outcomes.

Comparison of antimicrobial therapy termination in febrile and afebrile patients with acute cholangitis after drainage.

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

Prevalence of antibiotic use for childhood diarrhoea in Uganda after an ORS scale-up intervention: a repeated cross-sectional study.

BACKGROUND: Diarrhoea kills 500,000 children every year despite availability of cheap and effective treatment. In addition, a large number are inappropriately treated with antibiotics, which do not benefit the patient but can contribute to the development of antibiotic resistance. We investigated whether the prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda changed following a national intervention to increase the use of oral rehydration salts (ORS), and whether any socioeconomic characteristics were associated with antibiotic use. METHODS: A cross-sectional survey was conducted among caregivers of children under the age of five and among private health care providers and drug sellers in Uganda in 2014. This was compared to a similar survey among private health care providers, and the national demographic and health survey in Uganda in 2016. Logistic regression was used to find associations between antibiotic use and socioeconomic characteristics, and chi-square test and independent sample t-test were used to find significant differences between groups. RESULTS: The prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda decreased from 30.5% in 2014 to 20.0% (p < 0.001) in 2016. No associations between socioeconomic characteristics and the use of antibiotics were significant in both 2014 and 2016. CONCLUSIONS: The use of antibiotics in children with diarrhoeal disease decreased significantly in Uganda between 2014 and 2016. However, the extent of the contribution of the ORS scale-up programme to this decrease cannot be determined from this study.

Blood culture bottles meet the operating room: enhancing the diagnostic accuracy of infectious spondylitis through open microsurgical biopsy and intraoperative inoculation.

PURPOSE: Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. METHODS: This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. RESULTS: Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. CONCLUSIONS: We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis.

Extensively Antibiotic-Resistant Bacterial Infections in Trauma Cases Managed at the Médecins Sans Frontières Tertiary Orthopaedic Center in Mosul, Iraq: A Case Series.

The Médecins Sans Frontières Tertiary Orthopaedic Care center in Mosul, Iraq, provides reconstructive surgery, microbiological analysis, integrated infection prevention and control, and antibiotic stewardship services. Between May 2018 and February 2020, we recorded soft tissue and/or bone infections caused by gram-negative extensively drug-resistant (XDR) bacteria in 4.9% (13/266) of the admitted patients. The XDR bacteria identified among 12 patients in this case series were extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (n = 5, 41.7%) with intermediate sensitivity or resistance to imipenem and/or meropenem, Acinetobacter spp (n = 3, 25.0%; 2 Acinetobacter baumannii strains) resistant to imipenem and/or meropenem, Pseudomonas aeruginosa (n = 2, 16.7%) resistant to imipenem and meropenem, and extended-spectrum ß-lactamase-producing Proteus mirabilis (n = 2, 16.7%) resistant to meropenem. Most XDR isolates were sensitive only to colistin or polymyxin B, neither of which is available in Iraq. Therefore, the only treatment option was multiple rounds of surgical debridement and wound care. The infection was deemed cured before discharge in 7 patients (58.3%). Meanwhile, 4 patients (33.3%) were discharged with unhealed wounds, and outpatient follow-up was planned. One patient died in the intensive care unit of a referral hospital after developing septicemia postsurgery. XDR bacteria pose substantial health risks in Iraq. Thus, improving antimicrobial stewardship and accessibility to essential antibiotics is critical to address this issue.

Absence of a functional gut microbiome impairs host amino acid metabolism in the Pacific spiny dogfish (Squalus suckleyi).

Nitrogen recycling and amino acid synthesis are two notable ways in which the gut microbiome can contribute to host metabolism, and these processes are especially important in nitrogen limited animals. Marine elasmobranchs are nitrogen limited as they require substantial amounts of this element to support urea-based osmoregulation. However, following antibiotic-induced depletion of the gut microbiome elasmobranchs are known to experience a significant decline in circulating urea and employ compensatory nitrogen conservation strategies such as reduced urea and ammonia excretion. We hypothesized that the elasmobranch gut microbiome transforms dietary and recycled nutrients into amino acids, supporting host carbon and nitrogen balance. Here, using stable isotope analyses, we found that depleting the gut microbiome of Pacific spiny dogfish (Squalus suckleyi) resulted in a significant reduction to the incorporation of supplemented dietary 15N into plasma amino acids, notably those linked to nitrogen handling and energy metabolism, but had no effect on gut amino acid transport. These results demonstrate the importance of gut microbes to host amino acid pools and the unique nitrogen handling strategy of marine elasmobranchs. More broadly, these results elucidate how the gut microbiome contributes to organismal homeostasis, which is likely a ubiquitous phenomenon across animal populations.

A one health approach to tackling AMR and why gender matters: findings from pastoralist communities in Tanzania.

Introduction: Inappropriate use of antimicrobials is a major driver of AMR in low-resource settings, where the regulation of supply for pharmaceuticals is limited. In pastoralist settings in Tanzania, men and women face varying degrees of exposure to antibiotics due to gender relations that shape access and use of antimicrobials. For example, critical limitations in healthcare systems in these settings, including inadequate coverage of health services put people at risk of AMR, as families routinely administer self-treatment at home with antimicrobials. However, approaches to understanding AMR drivers and risk distribution, including the One Health approach, have paid little attention to these gender considerations. Understanding differences in access and use of antimicrobials can inform interventions to reduce AMR risk in community settings. This paper focuses on the gendered risk of AMR through a study of gender and social determinants of access to and use of antimicrobials in low-resource pastoralist settings in Tanzania. Methods: A mixed methods approach involving household surveys, interviews and ethnographic participant observation in homes and sites of healthcare provision was used, to investigate access and administration of antibiotics in 379 adults in Naiti, Monduli district in northern Tanzania. A purposive sampling technique was used to recruit study participants and all data was disaggregated by sex, age and gender. Results: Gender and age are significantly associated with the use of antibiotics without a prescription in the study population. Young people aged 18-24 are more likely to use unprescribed antibiotics than older people and may be at a higher risk of AMR. Meanwhile, although more men purchase unprescribed antibiotics than women, the administration of these drugs is more common among women. This is because men control how women use drugs at the household level. Discussion: AMR interventions must consider the critical importance of adopting and implementing a gender-sensitive One Health approach, as gender interacts with other social determinants of health to shape AMR risk through access to and use of antimicrobials, particularly in resource-limited pastoralist settings.

A Comparison of Antibiotics' Resistance Patterns of E. coli and B. Subtilis in their Biofilms and Planktonic Forms.

BACKGROUND: A biofilm refers to a community of microbial cells that adhere to surfaces that are surrounded by an extracellular polymeric substance. Bacteria employ various defence mechanisms, including biofilm formation, to enhance their survival and resistance against antibiotics. OBJECTIVE: The current study aims to investigate the resistance patterns of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in both biofilms and their planktonic forms. METHODS: E. coli and B. subtilis were used to compare resistance patterns in biofilms versus planktonic forms of bacteria. An antibiotic disc diffusion test was performed to check the resistance pattern of biofilm and planktonic bacteria against different antibiotics such as penicillin G, streptomycin, and ampicillin. Biofilm formation and its validation were done by using quantitative (microtiter plate assay) and qualitative analysis (Congo red agar media). RESULTS: A study of surface-association curves of E. coli and B. subtilis revealed that surface adhesion in biofilms was continuously constant as compared to their planktonic forms, thereby confirming the increased survival of bacteria in biofilms. Also, biofilms have shown high resistance towards the penicillin G, ampicillin and streptomycin as compared to their planktonic form. CONCLUSION: It is safely inferred that E. coli and B. subtilis, in their biofilms, become increasingly resistant to penicillin G, ampicillin and streptomycin.

Applying Machine Learning for Antibiotic Development and Prediction of Microbial Resistance.

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field.

The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia.

INTRODUCTION: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. METHODS: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire® FilmArray Pneumonia Panel (BioFire® PN) results from critically ill patients. RESULTS: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. CONCLUSIONS: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.

Construction of luminescent dye@MOF platforms for sensing antibiotics with enhanced selectivity and sensitivity.

The fabrication of luminescent dye@MOF composites has received extensive attentions in the development of realistic sensing applications. Herein, based on two anionic In-MOFs with different pore structure (1 and 2), the charge and size dependent ion-exchange of cationic dyes was investigated, and consequently four luminescent dye@MOF composites (DMASM@1/2 and RhB@1/2) were successfully fabricated and importantly can be regarded as ideal platforms for better understanding of the factors affecting the construction of dye@MOF composites, which may closely related to a well match between the intrinsic properties and size/charge of the fluorescent molecules and the porosity, structure character of the MOF hosts. Furthermore, these four dye@MOF composites were utilized for sensing of different kinds of antibiotics, demonstrating enhanced selectivity and sensitivity. DMASM@1/2 demonstrated excellent selectivity and sensitivity for NFT and NFZ antibiotics, while RhB@1/2 exhibited excellent selectivity and sensitivity for MDZ and DTZ antibiotics. Systematic analysis of the detection mechanism revealed that different energy transfer efficiency and interaction between MOF frameworks and different types of guest dyes led to different selectivity and detection mechanisms for antibiotics. Moreover, high selectivity and sensitivity, low LOD and extraordinary recycling capacity of four dye@MOF composites in the detection of antibiotics promote their excellent prospect in the further practical application.

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.

Combined effect and mechanism of microplastic with different particle sizes and levofloxacin on developing Rana nigromaculata: Insights from thyroid axis regulation and immune system.

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants with other environmental pollutants, such as levofloxacin (LVFX). After 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, we measured the weight, snout-to-vent length (SVL), and development stages of Rana nigromaculata. Furthermore, we analyzed proteins and genes related to immune system and thyroid axis regulation, intestinal histological, and bioaccumulation of LVFX and MPs in the intestine and brain to further explore the toxic mechanism of co-exposure. We found MPs exacerbated the effect of LVFX on growth and development, and the order of inhibitory effects is as follows: LVFX-MP3>LVFX-MP1>LVFX-MP2. 0.1 and 1 µm MP could penetrate the blood-brain barrier, interact with LVFX in the brain, and affect growth and development by regulating thyroid axis. Besides, LVFX with MPs caused severer interference on thyroid axis compared with LVFX alone. However, 10 µm MP was prone to accumulating in the intestine, causing severe histopathological changes, interfering with the intestinal immune system and influencing growth and development through immune enzyme activity. Thus, we concluded that MPs could regulate the thyroid axis by interfering with the intestinal immune system.