Adjunctive intravesical EDTA-tromethamine treatment of a biofilm-associated recurrent Escherichia coli cystitis in a dog.

A 15-month-old spayed female greater Swiss mountain dog was brought to our clinic because of relapsing episodes of urinary tract infection, present since her adoption at 2 mo of age. A diagnosis of chronic bacterial cystitis associated with an invasive, biofilm-forming uropathogenic Escherichia coli was made with bladder-wall histology and fluorescent in situ hybridization analysis. Local treatment with EDTA-tromethamine (EDTA-Tris) infusions along with parenteral cefquinome and prophylactic measures (Type-A proanthocyanidins and probiotics) coincided with clinical and bacterial remission. The dog has been free of clinical signs of urinary tract infection for >4 y. Biofilm-forming uropathogenic E. coli can cause chronic, recurrent cystitis due to low antibiotic efficacy and should be considered in cases of recurrent cystitis in dogs, especially in the absence of identified predisposing factors. This case report describes the diagnostic and therapeutic options that were used to manage a case of this type. Key clinical message: Fluorescent in situ hybridization analysis may be considered in the diagnosis of chronic bacterial cystitis in dogs, and intravesical instillations of EDTA-Tris may be helpful in managing such cases.

Traitement adjuvant intravésical avec de l'EDTA-trométhamine chez un chien présentant une cystite récurrente à Escherichia coli formant des biofilmsUne chienne grand bouvier suisse stérilisée de 15 mois nous a été présentée pour des épisodes d'infection du tractus urinaire récidivants depuis son adoption à l'âge de 2 mois. Une cystite bactérienne chronique associée à un Escherichia coli uropathogène formant des biofilms a été identifiée par l'examen histologique de la paroi vésicale et par hybridation in situ fluorescente. Des instillations intravésicales d'EDTA et trométhamine (EDTA-Tris) en complément d'une antibiothérapie parentérale de courte durée (cefquinome) et de mesures prophylactiques (proanthocyanidines de type A et probiotiques) ont permis une guérison clinique et bactériologique de la cystite pendant plus de 4 ans. Les infections par Escherichia coli formant des biofilms peuvent causer des cystites chroniques récurrentes dues à une faible efficacité des antibiotiques et doivent être incluses dans le diagnostic différentiel des cystites récurrentes chez le chien, particulièrement en l'absence d'autre facteur prédisposant. Ce rapport propose des stratégies diagnostiques et thérapeutiques ayant permis la prise en charge d'un de ces cas.Message clinique clé :L'analyse par hybridation in situ fluorescente peut être envisagé dans le diagnostic de cystite bactérienne chronique chez les chiens, et l'instillation intravésicale d'EDTA-Tris peut être utile dans la gestion de tels cas.(Traduit par les auteurs).

The role of early use of Carbapenems perioperatively for urolithiasis with ESBL-producing Escherichia coli.

BACKGROUND: Urolithiasis combined with ESBL-producing E. coli is often difficult to control and leads to higher postoperative infection-related complications. This study was aim to explore the efficacy and necessity for early use of carbapenem antibiotics perioperatively in urolithiasis patients with urinary tract infections caused by ESBL-producing E. coli. METHODS: The study included a total of 626 patients who were separated into two groups: Group I (the ESBL-producing E. coli group) and Group II (the non-ESBL-producing E. coli group). Antibiotic susceptibility testing was performed and the two groups induced postoperative infection-related events were recorded. the efficacy of perioperative antibiotics was evaluated. RESULTS: All strains of E. coli in our research were sensitive to Carbapenems antibiotics. In addition to Carbapenems, the resistance rates of ESBL-producing E. coli to 6 other commonly used antibiotics were higher than those of non-ESBL-producing strains. Based on the preoperative antibiotic susceptibility test for the ESBL-producing E. coli group and the qSOFA score, the Carbapenems were more effective than the ß-lactamase inhibitors (p = 0.08), while for the non-ESBL-producing E. coli group, there was no difference in the treatment effects between Carbapenems, ß-lactamase inhibitors, Ceftazidime and Quinolones (p = 0.975). CONCLUSIONS: Carbapenem antibiotics significantly reduced the incidence of postoperative infection-related events compared with other types of antibiotics for ESBL-producing E. coli infections in patient with urolithiasis.

A study on selected responses and immune structures of broiler chickens with experimental colibacillosis with or without florfenicol administration.

BACKGROUND: Colibacillosis in broiler chickens is associated with economic loss and localized or systemic infection. Usually, the last resort is antibacterial therapy. Insight into the disease pathogenesis, host responses and plausible immunomodulatory effects of the antibacterials is important in choosing antibacterial agent and optimization of the treatment. Selected responses of broiler chickens experimentally infected with Escherichia coli (E. coli) and also those treated with florfenicol are evaluated in this study. Chickens (n = 70, 5 weeks old) were randomly assigned to four groups. The control groups included normal control (NC) and intratracheal infection control (ITC) (received sterile bacterial medium). The experimental groups consisted of intratracheal infection (IT) that received bacterial suspension and intratracheal infection with florfenicol administration (ITF) group. RESULTS: Florfenicol reversed the decreased albumin/globulin ratio to the level of control groups (p > 0.05). Serum interleukin 10 (IL-10) and interferon-gamma (IFN-γ) concentrations decreased in IT birds as compared to NC group. Florfenicol decreased the serum interleukin 6 (IL-6) concentration as compared to IT group. Milder signs of inflammation, septicemia, and left shift were observed in the leukogram of the ITF group. Florfenicol decreased the severity of histopathological lesions in lungs and liver. Depletion of lymphoid tissue was detected in spleen, thymus and bursa of IT group but was absent in ITF birds. The number of colony forming units of E. coli in liver samples of ITF group was only slightly lower than IT birds. CONCLUSIONS: Experimental E. coli infection of chickens by intratracheal route is associated with remarkable inflammatory responses as shown by changes in biochemical and hematological parameters. Histopathological lesions in lymphoid organs (especially in the spleen) were also prominent. Florfenicol has positive immunomodulatory effects and improves many of the lesions before the full manifestation of its antibacterial effects. These effects of florfenicol should be considered in pharmacotherapy decision-making process.

Third-generation cephalosporin resistant Escherichia coli in dogs and cats in Germany in 2019-2021.

OBJECTIVES: Antimicrobial resistance (AMR) poses a worldwide challenge, threatening global health. The objective of this research was to determine the 3rd generation cephalosporin resistance (3GCR) proportion in Escherichia (E.) coli isolated from clinical samples of dogs and cats in Germany. METHODS: The study utilized result data from antimicrobial susceptibility testing (AST) of isolates obtained from diagnostic samples collected from dogs and cats send in for bacterial examination. Data includes AST results from 3,491 veterinary practices in Germany spanning the years 2019 to 2021, representing 33.1% of practices and clinics nationwide. Out of 175,171 clinical samples, a total of 25,491 E. coli strains (14,6%) were evaluated for their susceptibility to antimicrobials, in particular the 3rd generation cephalosporin cefovecin, but also aminoglycosides (gentamicin, GEN), fluoroquinolones (enrofloxacin, ENR), tetracyclines (doxycycline), phenicols (chloramphenicol), folate pathway inhibitors (sulfamethoxazole + trimethoprim), and nitrofurans (nitrofurantoin). RESULTS: The cefovecin resistance proportion was 11.6% in the study period. Geographical analysis showed local variations in 3GCR in E. coli of ±3%. Regarding all E. coli isolates investigated, resistance proportions were observed as follows: 12% for sulfamethoxazole-trimethoprim, 7% for enrofloxacin, 8% for chloramphenicol and 4% for gentamicin. Notably, 3GCR E. coli showed significantly higher resistance proportions, specifically 30% for sulfamethoxazole-trimethoprim, 28% for chloramphenicol, 18% for enrofloxacin and 14% for gentamicin. CONCLUSIONS: This study represents the first of its kind to utilize an extensive dataset encompassing dogs and cats across Germany. Companion animals have close contact to their owners and transmission of 3GCR between them is likely as well as acquisition from other environmental sources. Resistance proportions (6.7%) against the antibiotic ceftazidime as reported by the German AMR surveillance for human medicine were lower than in our veterinary data. Our study provides an overview of the current 3GCR resistance proportion in Germany and demonstrates the importance of integrated AMR monitoring.

[Nine-year trend in Escherichia coli resistance to ciprofloxacin: cross-sectional study in a hospital in Colombia]. / Nueve años de tendencia en la resistencia a ciprofloxacina por Escherichia coli: estudio transversal en un hospital de Colombia.

Ciprofloxacin is a critically important antibiotic for human health. The increase of Escherichia coli resistance to ciprofloxacin is a global public health problem due to its importance in the treatment of complicated urinary tract infections and other serious infections; however, its prescription is high in the Colombian Caribbean. The objective was to determine the resistance trend of E. coli to ciprofloxacin in a Colombian hospital of high complexity. From antibiogram reports, isolates were categorized according to Clinical and Laboratory Standards Institute criteria for each year studied; proportions were calculated and differences in sensitivity were explored using the χ2 test. The Cochran-Armitage test was used to evaluate the resistance trend. Significance was considered when p-value ≤ 0.05. In total, 6,848 isolates were analyzed, and 49.31% resistance was found. According to origin, the highest resistance was in community samples (51.96% - 95%CI: 50.51; 53.41), and by type of sample, in skin and tissues (61.76% - 95%CI: 56.96; 66.35) and urine (48.97% - 95%CI: 47.71; 50.23). Increasing trends were observed for resistance per year (p < 0.0001), community samples (p = 0.0002) and urine (p < 0.0001). Resistance to ciprofloxacin is high and tends to increase in the community and in urine, exceeding the limit established for its use at the ambulatory level, which is of concern due to the high prescription of fluoroquinolones in the locality.

La ciprofloxacina es un antibiótico de importancia crítica para la salud humana. El aumento de la resistencia de Escherichia coli a ciprofloxacina es un problema de salud pública global por su importancia en el tratamiento de infecciones urinarias complicadas y otras infecciones graves; sin embargo, su prescripción es alta en el caribe colombiano. El objetivo fue determinar la tendencia de resistencia de E. coli a ciprofloxacina en un hospital colombiano de alta complejidad. A partir de reportes de antibiogramas, los aislados fueron categorizados según los criterios del Instituto de Normas Clínicas y de Laboratorio de los Estados Unidos para cada año estudiado; se calcularon proporciones y se exploraron diferencias en la sensibilidad con pruebas χ2. Se utilizó la prueba de Cochran-Armitage para evaluar la tendencia de la resistencia. Valores de p ≤ 0,05 se consideraron significativos. Se analizaron 6.848 aislados, encontrándose una resistencia de 49,31%. Según el origen, la resistencia más alta fue en muestras comunitarias (51,96% - IC95%: 50,51; 53,41), y por tipo de muestra, en piel y tejidos (61,76% - IC95%: 56,96; 66,35) y orina (48,97% - IC95%: 47,71; 50,23). Se halló una tendencia al aumento en la resistencia por año (p < 0,0001), en muestras comunitarias (p = 0,0002) y en orina (p < 0,0001). La resistencia a ciprofloxacina es alta y tiende al aumento en comunidad y en orina, superando el límite establecido para su uso a nivel ambulatorio, lo que es preocupante por la alta prescripción de fluoroquinolonas en la localidad.

A ciprofloxacina é um antibiótico extremamente importante para a saúde humana. O aumento da resistência da Escherichia coli à ciprofloxacina é um problema de saúde pública global devido à sua importância no tratamento de infecções complicadas do trato urinário e outras infecções graves; no entanto, sua prescrição é alta no caribe colombiano. O objetivo foi determinar a tendência de resistência da E. coli à ciprofloxacina em um hospital colombiano de alta complexidade. A partir de relatórios de antibiogramas, os isolados foram categorizados de acordo com os critérios do Instituto de Padrões Clínicos e Laboratoriais dos Estados Unidos para cada ano estudado; as proporções foram calculadas e as diferenças de sensibilidade foram exploradas com os testes χ2. O teste de Cochran-Armitage foi usado para avaliar a tendência de resistência. Os valores de p ≤ 0,05 foram considerados significativos. Um total de 6.848 isolados foi testado e foi encontrada uma taxa de resistência de 49,31%. Por origem, a resistência foi mais alta em amostras comunitárias (51,96% - IC95%: 50,51; 53,41) e, por tipo de amostra, em pele e tecidos (61,76% - IC95%: 56,96; 66,35) e urina (48,97% - IC95%: 47,71; 50,23). Foi encontrada uma tendência de aumento na resistência por ano (p < 0,0001), em amostras da comunidade (p = 0,0002) e na urina (p < 0,0001). A resistência à ciprofloxacina é alta e tende a aumentar na comunidade e na urina, excedendo o limite estabelecido para uso ambulatorial, o que é preocupante, dada a alta prescrição de fluoroquinolonas na localidade.

Protective effect of dihydromyricetin on intestinal epithelium in weaned pigs upon enterotoxigenic Escherichia coli challenge.

Dihydromyricetin (DMY), a natural flavonoid compound, are believed to prevent inflammatory response, dealing with pathogens and repairing the intestinal barrier. The objective of this study was to investigate whether DMY supplementation could attenuate intestinal damage in the context of enterotoxigenic Escherichia coli K88 (ETEC F4+) infection. After weaning, different litters of pigs were randomly assigned to one of the following treatments: (1) non-challenged control (CON, fed with basal diet); (2) ETEC-challenged control (ECON, fed with basal diet); and (3) ETEC challenge + DMY treatment (EDMY, fed with basal diet plus 300 mg kg-1 DMY). We observed a significant reduction in fecal Escherichia coli shedding and diarrhea incidence, but an increase in ADG in pigs of EDMY group compared to the pigs of ECON group. Relative to the pigs of ECON group, dietary DMY treatment decreased (P < 0.05) concentrations of the serum D-xylose, D-lactate and diamine oxidase (DAO), but increased the abundance of zonula occludens-1 (ZO-1) in the jejunum of pigs. In addition, DMY also decreased (P < 0.05) the number of S-phase cells and the percentage of total apoptotic epithelial cells of jejunal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Furthermore, DMY decreased the mRNA expression levels of critical immune-associated genes TLR4, NFκB, Caspase3, Caspase9, IL-1ß, IL-6, TNF-α and the protein p-NFκB and p-IκBα expressions of intestinal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Compared to the ECON group, DMY elevated (P < 0.05) the expression levels of ß-defensins PBD1, PBD2, PBD3, PBD129, as well as the abundance of secreted IgA in intestinal mucosae of the EDMY group. Thus, our results indicate that DMY may relieve intestinal integrity damage due to Escherichia coli F4.

Rapid determination of antibiotic susceptibility of clinical isolates of Escherichia coli by SYBR green I/Propidium iodide assay.

Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Infection Inspection: using the power of citizen science for image-based prediction of antibiotic resistance in Escherichia coli treated with ciprofloxacin.

Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its threat. This study uses citizen science and image feature analysis to profile the cellular features associated with antibiotic resistance in Escherichia coli. Between February and April 2023, we conducted the Infection Inspection project, in which 5273 volunteers made 1,045,199 classifications of single-cell images from five E. coli strains, labelling them as antibiotic-sensitive or antibiotic-resistant based on their response to the antibiotic ciprofloxacin. User accuracy in image classification reached 66.8 ± 0.1%, lower than our deep learning model's performance at 75.3 ± 0.4%, but both users and the model were more accurate when classifying cells treated at a concentration greater than the strain's own minimum inhibitory concentration. We used the users' classifications to elucidate which visual features influence classification decisions, most importantly the degree of DNA compaction and heterogeneity. We paired our classification data with an image feature analysis which showed that most of the incorrect classifications happened when cellular features varied from the expected response. This understanding informs ongoing efforts to enhance the robustness of our diagnostic methodology. Infection Inspection is another demonstration of the potential for public participation in research, specifically increasing public awareness of antibiotic resistance.

Extended-Spectrum ß-Lactamase and carbapenemase-producing Escherichia coli O157:H7 among diarrheic patients in Shashemene, Ethiopia.

BACKGROUND: The worldwide increase in multidrug resistance is a major threat to public health. One particular concern is the presence of Escherichia coli strains that carry Extended-Spectrum ß-Lactamase (ESBL) and Carbapenemase enzymes, which can make multiple antibiotics ineffective. This complicates treatment strategies and raises the risk of illness and death. The aim of this study was to isolate E. coli O157:H7, assess its susceptibility against antimicrobial agents, and determine the presence of ESBL and Carbapenemase production in stool samples collected from diarrheic patients in Shashemene, west Arsi, Ethiopia from July to November 2022. METHODS: The samples were cultured McConkey Agar and E. coli were isolated and identified by standard biochemical tests using API 20E. E. coli O157:H7 was further identified using sorbitol McConkey Agar and antisera for O157 antigen test. The antimicrobial susceptibility test was performed using the Kirby-Bauer disc diffusion method using different antibiotics. Each identified isolate was screened and tested for phenotypical ESBL and Carbapenemase production using combined disc method and modified carbapenem inactivation method, respectively. Bivariant and multivariant analyses were employed using a logistic regression model for further analysis and were interpreted based on the odds ratio and level of statistical significance at a p-value <0.05 with 95% confidence interval. RESULTS: E. coli O157:H7 strain was found from 9% (38/423) study participants. The majority of the participants [61.9% (262/423)] were males; and 19.1% (81/ 423) of the participants were under five children. Living in urban areas, having domestic animals, and ≥5 family size in the household were identified as statistically significant factors associated with E. coli O157:H7. Twenty-seven (71.1%) and 12 (31.6%) of the 38 E. coli O157:H7 isolates were phenotypically confirmed to be ESBL and carbapenemase producers, respectively. All isolates were resistant against Ampicillin, but sensitive to ciprofloxacin. High resistance to Ampicillin and Amoxicillin/Clavulanic acid was observed among the ESBL and carbapenemase producing isolates also. The extent of detection of multidrug resistant E. coli O157:H7 isolates against three or more classes of antimicrobial agents tested was alarmingly very high (84%). CONCLUSION: The E. coli O157:H7 isolates in this study showed a significant resistance to certain antimicrobials that were tested. The level of ESBL and Carbapenemase production among these isolates was found to be quite high. We observed a high resistance to Ampicillin and Amoxicillin/Clavulanic acid among the ESBL and carbapenemase producing isolates. Ciprofloxacin was found to be the most effective drug against both the ESBL producers and nonproducers.

Prevalence and risk factors for extended-spectrum ß-lactamase producing antimicrobial-resistant E. coli in urinary tract infections among inpatients in the tertiary hospitals in Zanzibar (Tanzania): a prospective cross-sectional study.

Introduction: Extended-spectrum ß-lactamase (ESBL) production among Enterobacteriaceae, such as E. coli, has been increasing worldwide, which causes treatment failure for urinary tract infections. Therefore, this study aimed to determine the prevalence and risk factors for the production of ESBL in E. coli from patients with urinary tract infections (UTI) in Zanzibar. Methods: a prospective cross-sectional study was conducted from January 2018 to December 2021 in Zanzibar. Data were retrieved from a routine bacteriological laboratory culture report from urine samples of 4306 patients at the Lancet Laboratory. In addition, the patient's social demographics and clinical data were retrieved by examining the medical records in the respective hospitals. All inpatients older than fifteen years diagnosed with urinary tract infections (UTI) and requested urine culture and sensitivity were included. The Chi-square and Fischer's exact tests were used to compare antibiotic resistance. In addition, a binary logistic regression analysis was used to predict ESBL production risk factors. Results: the prevalence of E. coli-producing ESBL was 13.4% (578/4030). Infection of ESBL. E. coli was prevalent in females 52.6% (n=304) compared to male patients, 47.4% (n=274), and the majority 38.8% (n=224), were people of young age, between 16-30 years. The average age of patients was 31.5±10.2 years, with minimum age of 16 years and a maximum age of 72 years. In multivariate analysis, results shown that previously hospitalised patients aOR: 6.35, 95% Cl 3.37-11.92; p=0.001, long hospital stays aOR: 10.34, 95% Cl 3.03-22.29; p <0.001, prior use of penicillin aOR: 7.78, 95% Cl 2.99-29.11; p < 0.001, and prior use of cephalosporin drugs aOR: 4.64, 95% Cl 2.99-9.96; p=0.001, were strongly associated with the emergence of ESBL-producing E. coli in urinary tract infection patients. ESBL E. coli showed high resistance to amoxicillin 99.5% (n=575), ampicillin 97.8.% (n=570), cotrimazaxole 86.2% (n=344), ceftriaxone 73.7% (n=344), ciprofloxacin 73.2% (n=423), and ceftaxime 59.5% (n=426). There was a less resistance to ampicillin -cloxacillin 44.3% (n=256), gentamicin 22.5% (n=22.5), and norfloxacin 18.9% (n=109) respectively. Isolates were shown to be more susceptible to meropenem at 1.6% (n=9). Conclusion: the overall prevalence of ESBL-producing E. coli is 13.4%. The risk of emergence ESBL was higher in patients with previous history of hospitalisation, long hospital stay, prior use of penicillin and cephalosporin drugs. High level of antimicrobial resistance observed against most commonly used antibiotics in treatment of urinary tract infections. The clinicians should rely on microbiological diagnosis in treatment of UTIs to reduce risk of treatment failure. Further study should be carried out to assess the prevalence and resistance pattern of other uropathogens and other risk factors.

High Prevalence of ESBL Genes in Commensal Escherichia coli of the Urinary Tract: Implications for Antibiotic Stewardship among Residents of Ghanaian Elderly Nursing Care Homes.

The emergence and spread of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) pose significant challenges to the treatment and control of urinary tract infections, particularly among vulnerable populations, such as the elderly living in nursing care homes. In this study, we investigated the occurrence of ESBL genes in commensal E. coli isolated from urine samples of 118 elderly individuals residing in Ghanaian nursing care homes. A total of 195 ESBL genes were detected among 41 E. coli isolated from the study participants. All the isolates harboured at least one ESBL gene, and the majority of them (70.1%) carried at least four ESBL genes. Among the ESBL genes detected, CTXM825 was the predominant (14.1%). In antimicrobial susceptibility testing, 65.9% of the isolates showed resistance to cefepime, a fourth-generation cephalosporin, while 56.1% showed resistance to cefotaxime, a third-generation cephalosporin. Additionally, 46.3% of the isolates were multidrug-resistant, indicating resistance to antibiotics from multiple classes. In summary, we observed relatively high rates of resistance to antibiotics as well as alarming rates of ESBL genes in the isolated pathogens. These findings emphasise the urgent need for antimicrobial stewardship and infection control programmes to mitigate the spread of multidrug-resistant pathogens in nursing care homes.

Successful application of eculizumab in typical haemolytic uraemic syndrome.

A woman in her 40s with no medical history presented on hospital day #0 with 3 days of epigastric pain, nausea, vomiting and bloody diarrhoea. Initial blood work demonstrated acute kidney injury with metabolic acidosis with an elevated anion gap, thrombocytopenia, an elevated lactate dehydrogenase, and an undetectable haptoglobin. She was quickly diagnosed with haemolytic uraemic syndrome from Shiga toxin-producing O157:H7 Escherichia coli Her microangiopathic haemolytic anaemia and renal failure progressively worsened and only improved after the initiation of eculizumab, a monoclonal antibody directed against complement component C5. We report a case of Shiga toxin-producing E. coli-haemolytic uraemia syndrome with a complement-mediated component.

Opsoclonus-myoclonus-ataxia syndrome associated with bacterial urinary tract infection.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare acquired neurological disorder characterized by opsoclonus, focal or diffuse myoclonus, truncal instability and associated other cerebellar signs and ataxia. While predominantly affecting children, it can rarely manifest in adults and could be associated with infections, paraneoplastic syndrome, drugs or other neurological disorders. We present a case of an elderly gentleman presenting with OMAS associated with a culture-positive urinary tract infection with Escherichia coli, successfully treated with antibiotics and immunoglobulins resulting in significant recovery.

Efficient and Selective, In Vitro and In Vivo, Antimicrobial Photodynamic Therapy with a Dicationic Chlorin in Combination with KI.

Various cationic photosensitizers employed in antimicrobial photodynamic therapy (aPDT) have the ability to photoinactivate planktonic bacteria under conditions of low phototoxicity to mammalian cells and without generating antimicrobial resistance (AMR). However, the photoinactivation of biofilms requires orders-of-magnitude higher photosensitizer concentrations, which become toxic to host cells. Remarkably, the bactericidal effect of a dicationic di-imidazolyl chlorin toward planktonic S. aureus and E. coli was observed in this work for concentrations below 400 nM under illumination at 660 nm and below 50 µM for the corresponding biofilms. At the latter concentrations, the chlorin is phototoxic toward human keratinocyte cells. However, in the presence of 50 mM KI, bactericidal concentrations are reduced to less than 50 nM for planktonic bacteria and to less than 1 µM for biofilms. It is shown that the potentiation with KI involves the triiodide anion. This potentiation elicits a bactericidal effect without appreciable cytotoxicity to keratinocytes. It becomes possible to selectively inactivate biofilms with aPDT. An exploratory study treating mice with wounds infected with E. coli expressing GFP with 20 µM chlorin and 120 J cm-2 at 652 nm confirmed the potential of this chlorin to control localized infections.

α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration.

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

Modelling the implementation of narrow versus broader spectrum antibiotics in the empiric treatment of E. coli bacteraemia.

The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.

Research Note: Synergistic effect of isopropoxy benzene guanidine and colistin against mcr-1-positive Escherichia coli in vitro and in duck intestine infection models.

Colistin (CST) is considered as "agent of last resort" against gram-negative bacteria as feed additive. Its clinical effectiveness has reduced since the emergence of mcr-1 gene in ducks. Isopropoxy benzene guanidine (IBG), a new guanidine derivative, showed positive effects on improving animal weights and alleviating intestinal pathogens, therefore, the objective of this study was to evaluate the effect of this compound supplement with CST in ducks and explore the possibilities in feed additive. A total of fifteen duck-origin Escherichia coli carrying the mcr-1 gene were included in this study. A checkerboard microdilution assay was used to evaluate the in vitro antibacterial activity of IBG combined with CST against mcr-1-positive E. coli. A 3-by-2 time-kill array of IBG (16, 32, and 64 µg/mL) and CST (1/2 MIC and 1/4 MIC) over 24 hours was utilized to characterize the activity of the agents alone and in combination against E. coli strain 1 in vitro. The intestinal colonization model was used to evaluate the in vivo effect of IBG combined with CST. These results indicated that the combination of IBG plus CST showed a synergistic effect against all clinical isolates (FICI < 0.5). The bacterial burden was reduced by more than 2 log10 CFU/mL when E. coli strain 1 was tested with 1/2 MIC CST plus 64 µg/mL IBG for 24 h. Further experiments in vivo demonstrated that the CST combined with IBG was able to increase duck weights, reduced intestinal pathogenic E. coli and showed a synergistic antibacterial effect. Combination of CST (4 mg/kg b.w.) plus IBG (32 or 64 mg/kg b.w.) achieved 1.84 to 3.29 log10 CFU/g killing after 7 d of therapy, which was significantly different from that in the challenge control group (p<0.05). In summary, our study demonstrated the potential use of IBG as feed additive for veterinary purposes in ducks and provided new insights into overcoming resistance in the future.

Sulfonamide resistance evaluation in five animal species and first report of sul4 in companion animals.

Sulfonamides are one of the oldest groups of antibacterial agents with a broad-spectrum, used as first line treatment in bacterial infections. Their widespread use produced a selective pressure on bacteria, as observed by the high incidence of sulfonamides resistance mainly in Gram negative bacteria isolated from animals. In this research, the presence of sulfonamide resistance genes (sul1, sul2, sul3, and sul4) in phenotypically resistant Escherichia coli isolates has been studied. These genes were amplified in isolates recovered from five animal species, with different interactions to humans: cattle, swine, poultry as livestock, and dogs and cats as companion animals. Isolates were collected according to their phenotypic resistance, and the magnetic bead-based Luminex technology was applied to simultaneously detect sul target genes. The frequency of sul genes was highest in swine, among livestock isolates. The sul1 and sul2 were the most frequently sulfonamide resistance genes detected in all phenotypically resistant isolates. Notably, in companion animals, with a closest interaction with human, sul4 gene was detected. To our knowledge, this is the first report of the presence of sul4 gene in E. coli collected from animals, whereas previously the presence of this gene was reported in environmental, municipal wastewater and human clinical isolates. These results highlighted the importance of continuous antimicrobial resistant genes monitoring in animal species, with a special care to companion animals.

Antimicrobial Resistance in Uropathogenic Escherichia coli Strains Isolated from Relapses from Recurrent Urinary Tract Infections.

Little is known about the characteristics of uropathogenic Escherichia coli (UPEC) associated with recurrent urinary tract infections (RUTIs). The present study aimed to analyze the phenotypic antimicrobial resistance of recurrent UPEC isolates attributable to either relapse or reinfection. A total of 140 E. coli strains were isolated from 70 outpatients with RUTIs. All isolates were analyzed by random amplified polymorphic DNA-polymerase chain reaction to evaluate genetic similarity between the first and second isolates. We found that 64.2% (45/70) of outpatients had a relapse with the primary infecting E. coli strain and 35.7% (25/70) had reinfection with a new E. coli strain. Compared with reinfecting strains, relapse UPEC isolates exhibited much higher antimicrobial resistance; 89% of these isolates were multidrug-resistant and 46.6% were extended-spectrum ß-lactamase producers. Our study provides evidence that RUTIs are mainly driven by the persistence of the original strain in the host (relapses) despite appropriate antibiotic treatments, and only RUTIs attributed to relapses seem to favor multidrug resistance in UPEC isolates.

Lipase-copper complex/chitosan microspheres; loaded with attapulgite used for the treatment of E. coli-induced diarrhea.

Diarrhea is a globally major problem especially Escherichia coli induced diarrhea becoming fatal nowadays in developing countries. Colon-targeted chitosan microspheres (Ms) comprising of lipase­zinc and lipase­copper complexes were prepared, loaded with Attapulgite (Cts-Li-Zn-ATG/Ms and Cts-Li-Cu-ATG/Ms) for the treatment of bacterial diarrhea. Thin layer chromatography (TLC) and Fourier-transform infrared spectroscopy (FTIR) studies were used for confirmation of proposed lipase-metal complexes. Ms showed particle size range 18 ± 0.24 to 23 ± 0.83 µm, zeta potential -13.7 ± 0.71 to -29.3 ± 1.34 mV, PDI 0.5 ± 0.04 to 1.0 ± 0.07 and hemolytic activity was found to be <5 ± 1.25 %. After coating with Eudragit S-100 for colon targeting, in-vitro % drug release of ATG at pH 7.4 was 80 ± 0.21 % for Eud-Cts-Li-Zn-ATG/Ms while it was increased to 83 ± 0.54 % for Eud-Cts-Li-Cu-ATG/Ms within 7 h, respectively. In-vivo anti-diarrheal activity of Eud-Cts-Li-Zn-ATG/Ms and Eud-Cts-Li-Cu-ATG/Ms was performed by oral challenge on albino mice having infectious diarrhea colonized with E. coli. Results revealed significant anti-diarrheal effect of proposed Eud-Cts-Li-Cu-ATG/Ms in terms of weight gain from 24 ± 0.12 g to 26.05 ± 0.31 g, which was 2-fold increase as compared to Eud-Cts-Li-Zn-ATG/Ms. Conclusively, Eud-Cts-Li-Cu-ATG/Ms provides an innovative alternate for the treatment of bacterial diarrhea with additional support of chitosan and lipase for nutritional support and immunity which was compromised in diarrheal patients.