Resistência antimicrobiana na infecção urinária em unidade de terapia intensiva / Antimicrobial resistance in urinary tract infection in the intensive care unit / Resistencia a los antimicrobianos en la infección del tracto urinario en la unidad de cuidados intensivos

A infecção do trato urinário (ITU) nada mais é do que o acometimento das vias urinárias por microrganismo. Entre as infecções hospitalares de maior incidência está a infecção do trato urinário, acometendo mais mulheres do que homens. Uma das possíveis causas dessa infecção, em pacientes na unidade de terapia intensiva (UTI), é o uso de cateter vesical. Seu tratamento inadequado pode ocasionar uma pielonefrite, podendo adentrar à circulação sanguínea, gerando uma infecção sistêmica e levar o paciente a óbito. A resistência antimicrobiana é uma das principais dificuldades encontrada em UTI sendo considerado um problema de saúde pública. O objetivo deste trabalho foi realizar um breve relato, baseado na literatura, sobre a resistência antimicrobiana na infecção urinária em unidade de terapia intensiva adulta. Em ambientes hospitalares o principal microrganismo causador de ITU é Escherichia coli, sendo 55,5% das culturas positivas estão associadas a procedimentos invasivos, como as sondas vesicais de demora, como consequência este é o microrganismo que mais apresenta resistência aos antimicrobianos utilizados como a ampicilina, trimetoprima e ciprofloxacino. O uso indiscriminado de antibióticos deixa em evidência a necessidade de análise criteriosa da real necessidade de qual antimicrobianos usar, tempo de uso e forma correta de administração. Portanto é necessária a ação dos profissionais de saúde frente a atenção ao paciente, desde a higiene das mãos, uso do cateter, quando necessário observar a real necessidade do uso do antimicrobianos e que esse seja feito após cultura e antibiograma.

Urinary tract infection (UTI) is nothing more than the involvement of the urinary tract by a microorganism. Among the hospital infections with the highest incidence is urinary tract infections, affecting more women than men. One of the possible causes of this infection in patients in the intensive care unit (ICU) is the use of a bladder catheter. Its inadequate treatment can cause pyelonephritis, which can enter the bloodstream, generating a systemic infection and leading the patient to death. Antimicrobial resistance is one of the main difficulties encountered in ICUs and is considered a public health problem. The objective of this study was to present a brief report, based on the literature, on antimicrobial resistance in urinary tract infections in an adult intensive care unit. In hospital environments, the main microorganism that causes UTI is Escherichia coli, and 55.5% of positive cultures are associated with invasive procedures, such as indwelling urinary catheters, as a consequence, this is the microorganism that is most resistant to antimicrobials used, such as ampicillin, trimethoprim and ciprofloxacin. The indiscriminate use of antibiotics highlights the need for a careful analysis of the real need for which antimicrobials to use, time of use, and correct form of administration. Therefore, it is necessary for the action of health professionals in the care of the patient, from the hygiene of the professional to, the use of the catheter, when necessary to observe the real need for the use of antimicrobials and that this is done after culture and antibiogram.

La infección del tracto urinario (ITU) no es más que la afectación de las vías urinarias por un microorganismo. Entre las infecciones hospitalarias con mayor incidencia se encuentra la infección del tracto urinario, que afecta más a mujeres que a hombres. Una de las posibles causas de esta infección en pacientes en la unidad de cuidados intensivos (UCI) es el uso de una sonda vesical. Su tratamiento inadecuado puede causar pielonefritis, la cual puede ingresar al torrente sanguíneo, generando una infección sistémica y llevando al paciente a la muerte. La resistencia a los antimicrobianos es una de las principales dificultades encontradas en las UCI y se considera un problema de salud pública. El objetivo de este estudio fue presentar un breve informe, basado en la literatura, sobre la resistencia antimicrobiana en infecciones del tracto urinario en una unidad de cuidados intensivos de adultos. En ambientes hospitalarios, el principal microorganismo causante de ITU es Escherichia coli, y el 55,5% de los cultivos positivos están asociados a procedimientos invasivos, como sondas vesicales permanentes, por lo que este es el microorganismo más resistente a los antimicrobianos utilizados, como la ampicilina. ., trimetoprima y ciprofloxacino. El uso indiscriminado de antibióticos pone de relieve la necesidad de un análisis cuidadoso de la necesidad real de qué antimicrobianos utilizar, el momento de uso y la forma correcta de administración. Por lo tanto, es necesaria la actuación de los profesionales de la salud en el cuidado del paciente, desde la higiene del profesional, uso del catéter, cuando sea necesario observar la necesidad real del uso de antimicrobianos y que este se realice previo cultivo y antibiograma.

Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection.

We rationally designed a bacteriophage cocktail to treat a 56-year-old male liver transplant patient with complex, recurrent prostate and urinary tract infections caused by an extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) (UCS1). We screened our library for phages that killed UCS1, with four promising candidates chosen for their virulence, mucolytic properties, and ability to reduce bacterial resistance. The patient received 2 weeks of intravenous phage cocktail with concomitant ertapenem for 6 weeks. Weekly serum and urine samples were collected to track the patient's response. The patient tolerated the phage therapy without any adverse events with symptom resolution. The neutralization of the phage activity occurred with sera collected 1 to 4 weeks after the first phage treatment. This was consistent with immunoassays that detected the upregulation of immune stimulatory analytes. The patient developed asymptomatic recurrent bacteriuria 6 and 11 weeks following the end of phage therapy-a condition that did not require antibiotic treatment. The bacteriuria was caused by a sister strain of E. coli (UCS1.1) that remained susceptible to the original phage cocktail and possessed putative mutations in the proteins involved in adhesion and invasion compared to UCS1. This study highlights the utility of rationally designed phage cocktails with antibiotics at controlling E. coli infection and suggests that microbial succession, without complete eradication, may produce desirable clinical outcomes.

The Short-Chain Fatty Acids Propionate and Butyrate Augment Adherent-Invasive Escherichia coli Virulence but Repress Inflammation in a Human Intestinal Enteroid Model of Infection.

Short-chain fatty acids (SCFAs), which consist of six or fewer carbons, are fermentation products of the bacterial community that inhabits the intestine. Due to an immunosuppressive effect on intestinal tissue, they have been touted as a therapeutic for inflammatory conditions of the bowel. Here, we study the impact of acetate, propionate, and butyrate, the three most abundant SCFAs in the intestine, on gene expression in the intestinal pathobiont adherent-invasive Escherichia coli. We pair this with adherence, invasion, and inflammation in Caco-2 and human intestinal enteroid (HIE)-derived monolayer models of the intestinal epithelium. We report that propionate and butyrate upregulate transcription of adherent-invasive Escherichia coli (AIEC) flagellar synthesis genes and decrease expression of capsule assembly and transport genes. These changes are predicted to augment AIEC invasiveness. In fact, SCFA supplementation increases AIEC adherence to and invasion of the Caco-2 monolayer but has no effect on these parameters in the HIE model. We attribute this to the anti-inflammatory effect of propionate and butyrate on HIEs but not on Caco-2 cells. We conclude that the potential of SCFAs to increase the virulence of intestinal pathogens should be considered in their use as anti-inflammatory agents. IMPORTANCE The human terminal ileum and colon are colonized by a community of microbes known as the microbiota. Short-chain fatty acids (SCFAs) excreted by bacterial members of the microbiota define the intestinal environment. These constitute an important line of communication within the microbiota and between the microbiota and the host epithelium. In inflammatory conditions of the bowel, SCFAs are often low and there is a preponderance of a conditionally virulent bacterium termed adherent-invasive Escherichia coli (AIEC). A connection between SCFA abundance and AIEC has been suggested. Here, we study AIEC in monoculture and in coculture with human intestinal enteroid-derived monolayers and show that the SCFAs propionate and butyrate increase expression of AIEC virulence genes while concurrently bolstering the intestinal epithelial barrier and reducing intestinal inflammation. While these SCFAs have been promoted as a therapy for inflammatory bowel conditions, our findings demonstrate that their effect on bacterial virulence must be considered.

Bioengineered phytomolecules-capped silver nanoparticles using Carissa carandas leaf extract to embed on to urinary catheter to combat UTI pathogens.

Rising incidents of urinary tract infections (UTIs) among catheterized patients is a noteworthy problem in clinic due to their colonization of uropathogens on abiotic surfaces. Herein, we have examined the surface modification of urinary catheter by embedding with eco-friendly synthesized phytomolecules-capped silver nanoparticles (AgNPs) to prevent the invasion and colonization of uropathogens. The preliminary confirmation of AgNPs production in the reaction mixture was witnessed by the colour change and surface resonance plasmon (SRP) band at 410nm by UV-visible spectroscopy. The morphology, size, crystalline nature, and elemental composition of attained AgNPs were further confirmed by the transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD) technique, Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The functional groups of AgNPs with stabilization/capped phytochemicals were detected by Fourier-transform infrared spectroscopy (FTIR). Further, antibiofilm activity of synthesized AgNPs against biofilm producers such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were determined by viability assays and micrographically. AgNPs coated and coating-free catheters performed to treat with bacterial pathogen to analyze the mat formation and disruption of biofilm formation. Synergistic effect of AgNPs with antibiotic reveals that it can enhance the activity of antibiotics, AgNPs coated catheter revealed that, it has potential antimicrobial activity and antibiofilm activity. In summary, C. carandas leaf extract mediated synthesized AgNPs will open a new avenue and a promising template to embed on urinary catheter to control clinical pathogens.

Meta-analysis identifies the effect of dietary multi-enzyme supplementation on gut health of pigs.

Gut health though is not well defined the role of gastrointestinal tract is vital if an animal must perform well. Apart from digestion, secretion, and absorption gut is harbored with consortium of microbiota which plays a key role in one's health. Enzymes, one of the alternatives for antibiotics with beneficial effects on digestion and consistency of food and its effect on gut health. The effect of enzyme supplementation on gut health is not well established and the objective of this meta-analysis is to investigate if the enzyme supplement has influence on gut. This meta-analysis includes 1221 experiments which has single enzyme studies and or studies with multiple enzyme complexes but not challenged. The ratio of Lactobacillus and E. coli is related to ADFI which showed comparatively lower negative correlation coefficient, with - 0.052 and - 0.035, respectively, whose I2 values are below 25%, showing that these studies show a significantly lower level of heterogeneity. Correlation between villus height, crypt depth, their ratio and fatty acid is also assessed, and it showed that when the animal is supplemented with two enzyme complexes resulted in positive gut health rather than the single or more than two enzymes.

Anti-Adhesion Effects of Lactobacillus Strains on Caco-2 Cells Against Escherichia Coli and Their Application in Ameliorating the Symptoms of Dextran Sulfate Sodium-Induced Colitis in Mice.

The beneficial effects of probiotics on ameliorating ulcerative colitis (UC) have attracted much attention in recent years. Nevertheless, the number of these identified probiotics is still limited. In addition, the adhesion abilities of probiotics are considered to be a key determinant for probiotic efficacy. However, the relationship between the adhesion abilities of probiotics and their role in ameliorating UC has been poorly studied to date. This study measured the adhesion abilities of four Lactobacillus strains to Caco-2 cells and their anti-adhesion effects on Caco-2 cells against pathogenic bacteria, as well as their application in ameliorating the symptoms of dextran sulfate sodium-induced UC, and further illustrated the relationship between these two potential probiotic properties of probiotics and their beneficial effects on UC. Results suggested that the adhesion abilities of the four tested Lactobacillus strains exists highly strain-specific and the mechanisms of their anti-adhesion effect on Caco-2 cells against Escherichia coli may be different. Moreover, all these strains had promising effects on ameliorating UC by reducing inflammatory response and improving the intestinal mucosal barrier function, as well as promoting the production of SCFAs. In conclusion, the four tested Lactobacillus strains can be considered as alternative dietary supplements in alleviating UC. In addition, it could be concluded that there is no significant correlation between the adhesion abilities of probiotics and their role in ameliorating UC, which further illustrated that the adhesion properties of probiotics in vitro may not be suitable as the key criterion for screening potential strains with UC-alleviating effects.

Formulation and Evaluation of a Clove Oil-Encapsulated Nanofiber Formulation for Effective Wound-Healing.

Wound-healing is complicated process that is affected by many factors, especially bacterial infiltration at the site and not only the need for the regeneration of damaged tissues but also the requirement for antibacterial, anti-inflammatory, and analgesic activity at the injured site. The objective of the present study was to develop and evaluate the natural essential oil-containing nanofiber (NF) mat with enhanced antibacterial activity, regenerative, non-cytotoxic, and wound-healing potential. Clove essential oil (CEO) encapsulated in chitosan and poly-ethylene oxide (PEO) polymers to form NFs and their morphology was analyzed using scanning electron microscopy (SEM) that confirmed the finest NFs prepared with a diameter of 154 ± 35 nm. The successful incorporation of CEO was characterized by Fourier transform infra-red spectroscopy (FTIR) and X-ray diffractometry (XRD). The 87.6 ± 13.1% encapsulation efficiency and 8.9 ± 0.98% loading of CEO was observed. A total of 79% release of CEO was observed in acidic pH 5.5 with 117% high degree of swelling. The prepared NF mat showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and non-cytotoxic behavior against human fibroblast cell lines and showed good wound-healing potential.

Analysis of risk factors, pathogenic bacteria of maternal sepsis in term pregnant women with positive blood culture during hospitalization.

ABSTRACT: The objective of this study was to evaluate the risk factors, pathogenic bacteria and drug sensitivity of maternal sepsis, and provide evidence for clinical prevention and treatment.A retrospective investigation of pregnant women with full-term maternal sepsis was performed to analyze the risk factors, pathogenic bacteria, and drug sensitivity of maternal sepsis.Univariate analysis showed that temperature, serum procalcitonin (PCT) and C-reactive protein (CRP) at admission, white blood cell count (WBC), PCT, CRP and neutrophilic granulocyte percentage (N%) during fever, premature rupture of membranes (PROM), antibiotic use within 1 week, mode of production, onset and duration of fever, between groups were statistically significant (P < .05). Logistic regression analysis showed that cesarean section was an independent risk factor for sepsis (OR = 11.839, 95%CI: 3.121-44.906). Apparent increase was found in body temperature (OR = 3.664, 95%CI: 1.722-7.795), duration of fever (OR = 1.953, 95%CI: 1.242-3.071), and PCT (OR = 1.080, 95%CI: 1.002-1.163). Also, increasing neutrophil ratio (OR = 1.180, 95%CI: 1.073-1.297) indicated a high possibility of maternal sepsis. The organism Escherichia coli (E. coli) was the most common pathogenic bacteria in the positive blood culture group (90%), and the sensitivity to carbapenems (meropenem and imipenem/cilastatin) was 100%, that to piperacillin-tazobactam and amoxicillin sulbactam was over 90%, and that to ceftazidime was 95%.Cesarean section was an independent risk factor for maternal sepsis in term pregnant women with positive blood culture. Besides, the E. coli was the most common pathogenic bacteria in the positive blood culture group. Antibiotics should be used in time and reasonably when the temperature was significantly increased with elevated PCT and N% after a cesarean section.

Distillation time effecting on the composition of Origanum floribundum essential oils and their antioxidant and antimicrobial activities.

The essential oils (EOs) of Origanum floribundum Munby, an aromatic and medicinal plant endemic in Algeria, were extracted by different hydrodistillation times (30 min, 1, 2 and 3 h) and analyzed by GC and GC-MS. The chromatographic analysis showed that thymol (32.7-45.0%), p-cymene (16.8-23.1%) and γ-terpinene (21.6-28.7%) were the most prominent components of the oils. The antioxidant ability was measured using the reductive potential, thiobarbituric acid reactive substances (TBARS) assay and the inhibition of free radicals DPPH● and ABTS●+. Antibacterial activity was assessed by the disc diffusion method against three bacteria (Escherichia coli, Staphylococcus aureus and Bacillus subtilis) and one fungus (Candida albicans). Minimal inhibitory concentrations (MICs) were determined using a microdilution method. Thymol is one of the compounds of EOs, which are widely reported as very biologically active. Although the oil isolated for 30 min was the less-thymol rich, it was the most active with all the antioxidant tests. In the most cases, the antimicrobial activity showed the best results with oils isolated for 30 min and 3 h (MIC = 0.25-1.75 µL/mL). These results suggest that it might be possible to isolate the EO from this plant for a minimum distillation time to obtain oil that can give maximum biological activities.

Adenosine and ATPγS protect against bacterial pneumonia-induced acute lung injury.

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, disrupts the alveolar-capillary barrier, triggering pulmonary vascular leak thus inducing acute lung injury (ALI). Extracellular purines, adenosine and ATP, protected against ALI induced by purified LPS. In this study, we investigated whether these purines can impact vascular injury in more clinically-relevant E.coli (non-sterile LPS) murine ALI model. Mice were inoculated with live E. coli intratracheally (i.t.) with or without adenosine or a non-hydrolyzable ATP analog, adenosine 5'-(γ-thio)-triphosphate (ATPγS) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATPγS 15 min prior or adenosine 3 h after E.coli insult significantly attenuated the E.coli-mediated increase in inflammatory responses. Furthermore, adenosine prevented weight loss, tachycardia, and compromised lung function in E. coli-exposed mice. Accordingly, treatment with adenosine or ATPγS increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATPγS downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATPγS mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.

Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.

Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, than untrained monocytes. Candida albicans, ß-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca2+ uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.

Variations of the Escherichia coli population in the digestive tract of broilers.

We explored the between-group and temporal variations in the intestinal Escherichia coli populations of broilers under experimental conditions, taking both antimicrobial resistance and virulence into consideration. Four replicates of 45 commercial chicks were reared in four animal facilities. On their first day of life (Day 0), they were orally inoculated with two extended-spectrum-cephalosporin-resistant (ESCR) E. coli (2.72 log10 CFU of a bla CMY-2- and 2.55 log10 CFU of a bla CTX-M-carrying E. coli). Faecal samples were then collected weekly and caecal samples were obtained from birds sacrificed on Days 21 or 42. The total, ESC-, ciprofloxacin- and gentamicin-resistant E. coli populations were enumerated on MacConkey (MC) and MC-supplemented media, and eight virulence-associated genes (VAGs) (iroN, iutA, iss, ompT, hlyF, vat, frzorf4 , and fyuA) were sought by PCR on isolates obtained on MC agar. The results showed significant between-group differences in the size of the resistant sub-populations and the presence of VAGs. Contrary to bla CTX-M-positive strains, bla CMY-positive strains persisted up to Day 42, but represented only a minor fraction of the total E. coli population. The ESC-, gentamicin- and ciprofloxacin-resistant populations decreased over time. Isolates obtained during the first week contained a mean of 5.1 VAGs. The percentages of some VAG profiles differed between faecal isolates on Day 41 and caecal isolates on Day 42. The fluctuations or differences between E. coli isolates according to group, age, and faecal or caecal origin need to be considered when designing experimental protocols and seeking to improve colibacillosis control. RESEARCH HIGHLIGHTS Temporal variations in the intestinal E. coli populations of broilers was studied. The antibiotic-resistant populations decreased over time. Virulence profiles differed between faecal isolates on Day 41 and caecal isolates on Day 42. Strains with the highest numbers of virulence genes were present during the first days.

Characterization and antibacterial action mode of bacteriocin BMP32r and its application as antimicrobial agent for the therapy of multidrug-resistant bacterial infection.

Multidrug-resistant (MDR) bacterial infection still poses a serious threat to public health, therefore, effective and safe antimicrobial agents are urgently needed. In this study, recombinant bacteriocin BMP32 (BMP32r) prepared by the Escherichia coli expression system had a broad-spectrum antibacterial activity even against some MDR bacteria and its minimum inhibitory concentration ranged from 9.2 to 36.8 mg/L. Furthermore, BMP32r showed good stable performance in heat, pH and storage. Moreover, the scanning electron microscope and transmission electron microscope revealed that BMP32r killed indicator strains through cell wall destruction, pore formation, and the membrane permeability increasing which was proved by propidium iodide uptake investigation. The wound healing of an animal MDR S. aureus infected model was promoted by BMP32r, and the safety was verified by the cytotoxicity assay that the viability of HFF cells remained 87.3% in even when the concentration of BMP32r was as high as 147.2 mg/L. In addition, no abnormalities or damages to major organs was found in vivo assessments after treatment with BMP32r. In conclusion, BMP32r has great potential to be developed as a safe antimicrobial agent to treat MDR bacterial infections.

Curcumin addition in diet of laying hens under cold stress has antioxidant and antimicrobial effects and improves bird health and egg quality.

Curcumin is an herbal component with several biological properties, and we highlight here the thermal stability, antioxidant and anti-inflammatory activity. We determined whether curcumin supplementation in the diets of laying hens under cold stress and naturally infected with Escherichia coli would control infection, and would have positive effects on overall health, as well as egg production and quality. We allocated 36 chickens that had been naturally infected with E. coli into two groups, with six replicates and three chickens per repetition: control group and curcumin group (200 mg curcumin/kg). The experimental period lasted 42 days, and fecal, blood and egg samples were collected at 1, 21 and 42 days We found that feces and eggs had lower total bacterial counts, E. coli counts and total coliform counts in the curcumin group at 21 and 42 days. In fresh eggs, the brightness and yellow intensity (b+) were significantly higher in the curcumin group. In stored eggs, higher specific gravity, albumen height and lower yolk pH were observed in the curcumin group. Fresh eggs collected and stored on day 42 showed lower levels of lipid peroxidation in the curcumin group, while the total antioxidant capacity in the stored eggs was significantly higher in the curcumin group. The curcumin group showed lower total leukocyte counts as a result of lower numbers of neutrophils and lymphocytes, as well as lower levels of total protein, alkaline phosphatase and alanine aminotransferase. Lower serum lipoperoxidation at 42 days was observed in the curcumin group, probably because of the higher activity of glutathione peroxidase and glutathione transferase in other words, because of antioxidant stimulation. Taken together, our findings suggest that curcumin supplementation in laying hens under cold stress and with colibacillosis has positive effects on infection control because of antioxidant stimulation.

Two-Dimensional Device with Light-Controlled Capability for Treatment of Cancer-Relevant Infection Diseases.

Concurrent infection in cancer treatment is the leading cause of high cancer mortality that requires urgent action. Currently developed diagnostic methods are hindered by the difficulty of rapidly and reliably screening small amounts of pathogens in the blood and then release pathogens for downstream analysis, limiting the advance of cancer concurrent infection diseases diagnosis and targeted treatment. Herein, we present a near-infrared (NIR) light-responsive black phosphorus (BP)-based device that effectively captures and releases pathogen for downstream drug-resistance analysis. The aptamer-modified BP nanostructures exhibit enhanced topographical interactions and binding capabilities with pathogen, enabling highly efficient and selective capture of pathogen in serum. NIR light irradiation induces BP nanostructure to generate a local thermal effect, which regulates the three-dimensional structure of the aptamer and causes efficient release of pathogen from the substrate surface. The released pathogen is resistant to ampicillin as demonstrated by downstream genetic analysis. The design of the functionalized light-controlled device for monitoring pathogen behavior shows great potential for assisting in cancer therapy and promoting personalized healthcare.

The changing resistance patterns of bacterial uropathogens in children.

BACKGROUND: Increased antimicrobial resistance is a problem in managing urinary tract infections (UTI). With this study we assessed the resistance patterns of urinary isolates in children with UTI between January 2017 and January 2018. METHODS: A retrospective cohort study was conducted. Among 5,443 isolates, a total of 776 UTI episodes in 698 patients were included. Patients' gender, age, voiding dysfunction, UTI history, prophylaxis status, and presence of vesicoureteral reflux were noted. Patients were divided into three age groups: group 1 for ages ≤12 months; group 2 for ages 13-60 months; and group 3 for ages >60 months. The susceptibilities of etiologic agents to different antimicrobials were explored. RESULTS: Median age was 54 months (range 1 month-21 years); male to female ratio was 1:5. The most common causative agent was Escherichia coli (83% of the cases), followed by Klebsiella pneumoniae (7.5%). Resistance to ampicillin (62.6%) and co-trimoxazole (39.8%) were remarkable in all isolates. Overall extended-spectrum beta-lactamase (ESBL) positivity was 23.5%. The highest resistance rates, higher ESBL positivity (28.6%), and K. pneumoniae frequency (13.5%) were observed in group 1. Ceftriaxone resistance was significantly low (0.5%) in the ESBL (-) group, which constituted the majority of the isolates. Higher resistance rates were observed among the patients on prophylaxis compared to those off prophylaxis (P < 0.001). CONCLUSION: Ceftriaxone can still be used for empirical treatment; however, initial urine culture results are crucial due to high ESBL positivity. Special consideration must be taken for patients under 1 year of age. Periodical surveillance studies are needed to explore the changing resistance patterns of uropathogens and modify treatment plans.

Zinc prevents intestinal epithelial barrier dysfunction induced by alpha-hemolysin-producing Escherichia coli 536 infection in porcine colon.

Zinc treatment is beneficial for infectious diarrhea or colitis. This study aims to characterize the pathomechanisms of the epithelial barrier dysfunction caused by alpha-hemolysin (HlyA)-expressing Escherichia coli in the colon mucosa and the mitigating effects of zinc ions. We performed Ussing chamber experiments on porcine colon epithelium and infected the tissues with HlyA-producing E. coli. Colon mucosa from piglets was obtained from a feeding trial with defined normal or high dose zinc feeding (pre-conditioning). Additional to the zinc feeding, zinc was added to the luminal compartment of the Ussing chamber. Transepithelial electrical resistance (TER) was measured during the infection of the living tissue and subsequently the tissues were immuno-stained for confocal microscopy. Zinc applied to the luminal compartment was effective in preventing from E. coli-induced epithelial barrier dysfunction in Ussing chamber experiments. In contrast, zinc pre-conditioning of colon mucosae when zinc ions were missing subsequently in the luminal compartment was not sufficient to prevent epithelial barrier impairment during E. coli infection. The pathological changes caused by E. coli HlyA were alterations of tight junction proteins claudin-4 and claudin-5, focal leak formation, and cell exfoliation which reflected the paracellular barrier defect measured by a reduced TER. In microscopic analysis of luminal zinc-treated mucosae these changes were absent. In conclusion, continuous presence of unbound zinc ions in the luminal compartment is essential for the protective action of zinc against E. coli HlyA. This suggests the usage of zinc as therapeutic regimen, while prophylactic intervention by high dietary zinc loads may be less useful.

Metal-Organic Framework/Ag-Based Hybrid Nanoagents for Rapid and Synergistic Bacterial Eradication.

Recent emerged metal-organic frameworks (MOFs), as superior drug carriers, provide novel strategies to combat pathogenic bacterial infections. Although various antibacterial metal ions can be easily introduced in MOFs for chemical bacterial ablation, such a single-model bactericidal method suffers from high-dose use, limited antibacterial efficiency, and slow sterilization rate. Hence, developing a dual bactericidal system is urgently required. Herein, we report an MOF/Ag-derived nanocomposite with efficient metal-ion-releasing capability and robust photo-to-thermal conversion effect for synergistic sterilization. The MOF-derived nanocarbon consisting of metallic zinc and a graphitic-like carbon framework is first synthesized, and then Ag nanoparticles (AgNPs) are evenly introduced via the displacement reaction between Zn and Ag+. Upon near-infrared irradiation, the fabricated nanoagents can generate massive heat to destroy bacterial membranes. Meanwhile, abundant Zn2+ and Ag+ ions are released to make chemical damage to bacterial intracellular substances. Systematic antibacterial experiments reveal that such dual-antibacterial effort can endow the nanoagents with nearly 100% bactericidal ratio for highly concentrated bacteria at a very low dosage (0.16 mg/mL). Furthermore, the nanoagents exhibit less cytotoxicity, which provides potential possibilities for the applications in the biological field. In vivo assessment indicates that the nanocomposites can realize rapid and safe wound sterilization and are expected to be an alternative to antibiotics. Overall, we present an easily fabricated structure-engineered nanocomposite with chemical and photothermal effects for broad-spectrum bacterial sterilization.

Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against Enterobacterales: the Importance of Heteroresistance for Growth Outcome.

Oral fosfomycin trometamol is licensed as a single oral dose for the treatment of uncomplicated urinary tract infections, with activity against multidrug-resistant uropathogens. The impact of interindividual variability in urinary concentrations on antimicrobial efficacy, and any benefit of giving multiple doses, is uncertain. We therefore performed pharmacodynamic profiling of oral fosfomycin, using a dynamic bladder infection in vitro model, to assess high and low urinary exposures following a single oral dose and three repeat doses given every 72 h, 48 h, and 24 h against 16 clinical isolates with various MICs of fosfomycin (8 Escherichia coli, 4 Enterobacter cloacae, and 4 Klebsiella pneumoniae isolates). Baseline fosfomycin high-level-resistant (HLR) subpopulations were detected prior to drug exposure in half of the isolates (2 E. coli, 2 E. cloacae, and 4 K. pneumoniae isolates; proportion, 1 × 10-5 to 5 × 10-4% of the total population). Fosfomycin exposures were accurately reproduced compared to mathematical modeling (linear regression slope, 1.1; R2, 0.99), with a bias of 3.8% ± 5.7%. All 5/5 isolates with MICs of ≤1 µg/ml had no HLR and were killed, whereas 8/11 isolates with higher MICs regrew regardless of exposure to high or low urinary concentrations. A disk diffusion zone of <24 mm was a better predictor for baseline HLR and regrowth. Administering 3 doses with average exposures provided very limited additional kill. These results suggest that baseline heteroresistance is important for treatment response, while increased drug exposure and administering multiple doses may not be better than standard single-dose fosfomycin therapy.

Techno-biofunctionality of mangostin extract-loaded virgin coconut oil nanoemulsion and nanoemulgel.

Techno-biofunctional characteristics of nanoemulsion and (nano)emulgel loaded with mangostin extracts were elucidated. Crude mangostins from mangosteen peels recovered by virgin coconut oil (VCO), mixed VCO and propylene glycol (PG), and pure PG were used. The extracts were loaded in the dispersed phase in the presence of mixed surfactants (Tween20/Span20) with a varying hydrophilic-lipophilic balance (HLB) from 10.2 to 15.1. Results showed that globular and uniformly distributed droplets of the nanoemulsion were observed. The small particle sizes (typically 18-62 nm) with the zeta potential of -39 to -54.5 mV were obtained when mixed emulsifiers with HLB values of 12.6 and 15.1 were employed. With HLB values of 12.6 and 15.1, nanoemulsions loaded with mangostin extracts prepared with mixed VCO-PG and pure PG-based extracts showed approximately a 2 to 3-fold lower droplet size diameter when compared with the VCO-based extract. For the stability test, all nanoemulsions were stable over three freeze-thaw cycles with some changes in pH, zeta potential, and droplet size. The DPPH● scavenging activity, H2O2 scavenging activity, reducing power and antibacterial activities (E. coli and S. aureus) of the nanoemulsions were greater than their corresponding bulk extracts. Nanoemulgels produced by embedding the nanoemulsions in a hydrogel matrix was homogeneous and creamy yellow-white in appearance. The nanoemulgels had a higher mangostin release (87-92%) than their normal emulgels (74-78%). Therefore, this study presented the feasibility of nanoemulsions and nanoemulgels loaded with mangostin extracts as a promising delivery system for bioactive polyphenol in food supplements, pharmaceuticals and cosmetics.