OBJECTIVE: We 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.
METHODS: French 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.
RESULTS: Previous 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]).
CONCLUSIONS: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

Ferrate (Fe(VI): HFeO4- /FeO42-), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of disinfection by-products. In this study, we assessed the disinfecting ability of potassium ferrate against a variety of microorganisms, including waterborne pathogens, under varying pH and water temperature conditions. We presented CT values, a metric of ferrate concentrations (C) and contact time (T), to quantify microbial inactivation rates. Among the tested microorganisms, human adenovirus was the least resistant to ferrate, followed by waterborne bacteria such as Escherichia coli and Vibrio cholerae, and finally, the protozoan parasite Giardia duodenalis. We further investigated the impact of two pH values (7 and 8) and two temperatures (5 and 25 °C) on microbial inactivation rates, observing that inactivation rates increased with lower pH and higher temperature. In addition to showcasing ferrate\'s capacity to effectively inactivate a range of the tested microorganisms, we offer a ferrate CT table to facilitate the comparison of the effectiveness of various disinfection methods.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy.
METHODS: All consecutive patients with a GNB-BSI from January 1st, 2021, to April 1st, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed.
RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset.
CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.

N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring or to the carboxamide nitrogen atom were prepared and studied for their inhibition of Escherichia coli DNA gyrase by supercoiling assay. Compared to inhibitors bearing the substituents at position 4 of the benzothiazole ring, the inhibition was attenuated by moving the substituent to position 3 and further to the carboxamide nitrogen atom. A co-crystal structure of (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex with E. coli GyrB24 (ATPase subdomain) was solved, revealing the binding mode of this type of inhibitor to the ATP-binding pocket of the E. coli GyrB subunit. The key binding interactions were identified and their contribution to binding was rationalised by quantum theory of atoms in molecules (QTAIM) analysis. Our study shows that the benzyl or phenethyl substituents bound to the benzothiazole core interact with the lipophilic floor of the active site, which consists mainly of residues Gly101, Gly102, Lys103 and Ser108. Compounds with substituents at position 3 of the benzothiazole core were up to two orders of magnitude more effective than compounds with substituents at the carboxamide nitrogen. In addition, the 6-oxalylamino compounds were more potent inhibitors of E. coli DNA gyrase than the corresponding 6-acetamido analogues.

Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children\'s age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.

This study aimed to develop a novel Gelatin silver oxide material for releasing nitric oxide bionanocomposite wound dressing with enhanced mechanical, chemical, and antibacterial properties for the treatment of diabetic wounds. The gelatin- silver oxide nanoparticles (Ag2O-NP) bio nanocomposite was prepared using chitosan and gelatin polymers incorporated with silver oxide nanoparticles through the freeze-drying method. The samples were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Results showed that the Ag2O-NP nanoparticles increased porosity, decreased pore size, and improved elastic modulus. The Ag2O-NP wound dressing exhibited the most effective antibacterial properties against Staphylococcus aureus and Escherichia coli. Among the samples, the wound dressing containing silver oxide nanoparticles demonstrated superior physical and mechanical properties, with 48% porosity, a tensile strength of 3.2 MPa, and an elastic modulus of 51.7 MPa. The fabricated wound dressings had a volume ratio of empty space to total volume ranging from 40% to 60%. In parallel, considering the complications of diabetes and its impact on the vascular system, another aspect of the research focused on developing a per2mediated wound dressing capable of releasing nitric oxide gas to regenerate damaged vessels and accelerate diabetic wound healing. Chitosan, a biocompatible and biodegradable polymer, was selected as the substrate for the wound dressing, and beta-glycerophosphate (GPβ), tripolyphosphate (TPP), and per2mediated alginate (AL) were used as crosslinkers. The chitosan-alginate (CS-AL) wound dressing exhibited optimal characteristics in terms of hole count and uniformity in the scanning electron microscope test. It also demonstrated superior water absorption (3854%) and minimal air permeability. Furthermore, the CS-AL sample exhibited an 80% degradation rate after 14 days, indicating its suitability as a wound dressing. The wound dressing was loaded with S-nitrosoglutathione (GSNO) powder, and the successful release of nitric oxide gas was confirmed through the grease test, showing a peak at a wavelength of 540 nm. Subsequent investigations revealed that the treatment of human umbilical vein endothelial cells (HUVECs) with high glucose led to a decrease in the expression of PER2 and SIRT1, while the expression of PER2 increased, which may subsequently enhance the expression of SIRT1 and promote cell proliferation activity. However, upon treatment of the cells with the modified materials, an increase in the expression of PER2 and SIRT1 was observed, resulting in a partial restoration of cell proliferative activity. This comprehensive study successfully developed per2-mediated bio-nanocomposite wound dressings with improved physical, mechanical, chemical, and antibacterial properties. The incorporation of silver oxide nanoparticles enhanced the antimicrobial activity, while the released nitric oxide gas from the dressing demonstrated the ability to mitigate vascular endothelial cell damage induced by high glucose levels. These advancements show promising potential for facilitating the healing process of diabetic wounds by addressing complications associated with diabetes and enhancing overall wound healing.

BACKGROUND: The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.
METHODS: From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.
RESULTS: Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for blaCTX-M, 11 (18.9%) for blaTEM, and 8 (33.3%) for blaNDM. Forty-six (52.3%) K. pneumoniae isolates had blaCTX-M, 27 (18.6%) blaTEM, and 26 (68.4%) blaNDM.
CONCLUSIONS: This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.

This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.

UNASSIGNED: Carbapenem resistant organisms (CROs) such as Acinetobacter baumannii (CRAb), Pseudomonas aeruginosa (CRPa), Escherichia coli (CREc), and Klebsiella pneumoniae (CRKp) have been identified by the World Health Organization (WHO) as global priority pathogens. The dissemination of these pathogens and clonal outbreaks within healthcare facilities are of serious concern, particularly in regions with limited resources. In Fiji, where healthcare services are primarily provided by public hospitals, understanding the extent and nature of this problem is essential for the development of effective patient management, prevention interventions and control strategies.
UNASSIGNED: CROs isolated from 211 (77.3%) non-sterile (urinary catheters, urine, sputum, wound swab, and endotracheal tube) and 62 (22.7%) normally sterile (blood, cerebrospinal fluid, intravascular catheter, and aspirates) body sites of 272 patients treated at the three major hospitals in Fiji, the Colonial War Memorial Hospital (CWMH), Lautoka Hospital (LTKH), and Labasa Hospital (LBSH), and outer peripheral health centres around Fiji, were analysed. Clinical and demographic patient data such as age, sex, admission diagnosis, admission and discharge dates, patient outcomes, date of death, start and end date of meropenem and colistin treatment were reviewed. These CRO isolates comprised A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae, that were prospectively collected at the microbiology laboratory of CWMH and LBSH from January 2020 through August 2021 and at the LTKH from January 2020 to December 2021. In addition, 10 retrospectively stored CRPa isolates collected from patients at the CWMH from January through December 2019, were also included in the study. All isolates were characterised using mass spectrometry, antimicrobial susceptibility testing, and whole genome sequencing. Phylogenetic relationships among the CROs were assessed through core genome single nucleotide polymorphism (SNP) analysis. The CRAb isolates were also compared to the CRAb isolates from CWMH isolated in 2016/2017 and 2019, along with CRAb isolates obtained from Fijian patients admitted to New Zealand hospitals in 2020 and 2021 from our retrospective study.
UNASSIGNED: Of 272 patients, 140 (51.5%) were male, the median (range) age of patients was 45 (<1-89) years, 161 (59.2%) were I-Taukei, 104 (38.2%) Fijians of Indian descent, and 7 (2.6%) were from other ethnic backgrounds. 234 (86.0%) of these 272 patients, had their first positive CRO sample collected ≥72 h following admission and the remaining 38 (14.0%) were isolated within 72 h following admission. Of the 273 CROs, 146 (53.5%) were collected at the CWMH, 66 (24.2%) LTKH, and 61 (22.3%) LBSH, while 62 (22.7%) were isolated from normally sterile sites and 211 (77.3%) from sites that are not sterile. Of 273 isolates, 131 (48.0%) were CRAb, 90 (33.0%) CRPa, 46 (16.8%) CREc, and 6 (2.2%) CRKp. Of 131 CRAb, 108 (82.4%) were ST2, with three distinct clones, all encoding bla OXA-23 and bla OXA - 66, while clone 3 also encoded bla NDM-1; bla OXA-23 was associated with two copies of ISAba1 insertion element, forming the composite transposon Tn2006. The first two CRAb ST2 clones were genetically linked to those isolated at CMWH 2016 through 2019, while the third was genetically linked to isolates from Fijian patients admitted to New Zealand hospitals in 2020 and 2021. Of CRPa, 65 (72.2%) were ST773 and carried β-lactamase genes bla NDM-1, bla OXA-50, and bla OXA-395. Of 10 retrospective CRPa isolates, all belonged to CRPa ST773 and carried bla NDM-1, bla OXA-50, and bla OXA-395. Of 46 CREc, 44 (95.7%) were ST410 and encoded bla NDM-7 on an IncX3 plasmid. Of 6 CRKp, 4 (66.7%) were ST16 and carried bla NDM-5 on an IncX3 plasmid. Other sequence types of CRPa (ST9, ST357, ST654, ST664), CRAb (ST25, ST374, ST499), CREc (ST167), and CRKp (ST45, ST336) were also detected. Of those receiving meropenem treatment in the prospective study, 30 (57.7%) received it inappropriately. Of 272 patients, 65 (23.9%) died within the 30 days after first positive CRO isolation.
UNASSIGNED: We identified nosocomial transmission of distinct clones of CRAb ST2, CRPa ST773, CREc ST410, and CRKp ST16 within and between the three major hospitals in Fiji. Moreover, community onset infections associated with CRPa, CREc, and CRAb were also detected. Of note, cross-border transmission of CRAb ST2 clone 3 strain between Fiji and New Zealand was also detected. These clones encoded an array of carbapenem resistance genes associated with mobile genetic elements, including plasmids, transposons, and integrative and conjugative elements, signifying their potential for increased mobility, further acquisition of resistance genes, and spread. Inappropriate use of meropenem was common. Of note, the majority of patients who died had acquired CRO during their hospital stay. These findings highlight the need for stringent IPC strategies focusing on catheter and ventilator management, meticulous wound care, rigorous sepsis control, consistent hand hygiene, effective use of disinfectants, and thorough sanitisation of both hospital environments and medical equipment in the three major hospitals in Fiji. Additionally, diligent surveillance of AMR and robust antimicrobial stewardship are crucial for effectively managing nosocomial infections.
UNASSIGNED: This project was funded by the Otago Medical School Foundations Trust (Dean\'s Bequest Fund) and a Fiji National University seed grant. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

BACKGROUND: Medical dressings are designed to promote wound healing and reduce infection. The aim of project is to investigate the effect of natural brown colored cotton dressings on the healing of infected wounds in E.coli animals.
METHODS: In this study, degreased white cotton gauze was used as the control group, with degreased brown cotton gauze and degreased bleached brown cotton gauze as the experimental group 1 and experimental group 2, to investigate the effect on the repair of post-infectious wound damage in animals by establishing an infected wound model in rats with E.coli as the infecting organism.
RESULTS: The ability to promote healing of infected wounds was investigated by analyzing the wound healing status, macroscopic wound healing rate, hematoxylin-eosin staining, Masson staining, secretion of inflammatory factors by Elisa assay. The result showed that at day 14 of wound healing, the macroscopic wound healing rate was greater than 98% for all three groups of dressings; the collagen content reached 49.85 ± 5.84% in the experimental group 1 and 53.48 ± 5.32% in the experimental group 2, which was higher than the control group; brown cotton gauze promotes skin wound healing by shortening the inflammatory period in both groups. The expression of three inflammatory factors THF-α, IL-2, and IL-8 and three cytokines MMP-3, MMP-8, and MMP-9 were lower than that of the control group.
CONCLUSIONS: It was found that natural brown cotton gauze has better repairing and promoting healing effect on infected wounds. It opens up the application of natural brown cotton gauze in the treatment of infected wounds.