The photo-based treatment technology simultaneously removes resistant bacteria and resistant genes from wastewater.

Because of the recent widespread usage of antibiotics, the acquisition and dissemination of antibiotic-resistance genes (ARGs) were prevalent in the majority of habitats. Generally, the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria (ARB) disinfection and ARGs degradation and even promote the proliferation of ARGs. Problematically, ARB and ARGs in effluent pose potential risks if they are not further treated. Photocatalytic oxidation is considered a promising disinfection technology, where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid (DNA) for ARB elimination and subsequent degradation of ARGs. This review aims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant (AR) from wastewater in recent years. We discuss the sources and transfer of ARGs in wastewater. The overall removal efficiencies of ultraviolet radiation (UV)/chlorination, UV/ozone, UV/H2O2, and UV/sulfate-radical based system for ARB and ARGs, as well as the experimental parameters and removal mechanisms, are systematically discussed. The contribution of photocatalytic materials based on TiO2 and g-C3N4 to the inactivation of ARB and degradation of ARGs is highlighted, producing many free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer (HGT) in wastewater. Finally, based on the reviewed studies, future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.

Iron-promoted zirconia-alumina supported Ni catalyst for highly efficient and cost-effective hydrogen production via dry reforming of methane.

Developing cost-effective and high-performance catalyst systems for dry reforming of methane (DRM) is crucial for producing hydrogen (H2) sustainably. Herein, we investigate using iron (Fe) as a promoter and major alumina support in Ni-based catalysts to improve their DRM performance. The addition of iron as a promotor was found to add reducible iron species along with reducible NiO species, enhance the basicity and induce the deposition of oxidizable carbon. By incorporating 1 wt.% Fe into a 5Ni/10ZrAl catalyst, a higher CO2 interaction and formation of reducible "NiO-species having strong interaction with support" was observed, which led to an ∼80% H2 yield in 420 min of Time on Stream (TOS). Further increasing the Fe content to 2wt% led to the formation of additional reducible iron oxide species and a noticeable rise in H2 yield up to 84%. Despite the severe weight loss on Fe-promoted catalysts, high H2 yield was maintained due to the proper balance between the rate of CH4 decomposition and the rate of carbon deposit diffusion. Finally, incorporating 3 wt.% Fe into the 5Ni/10ZrAl catalyst resulted in the highest CO2 interaction, wide presence of reducible NiO-species, minimum graphitic deposit and an 87% H2 yield. Our findings suggest that iron-promoted zirconia-alumina-supported Ni catalysts can be a cheap and excellent catalytic system for H2 production via DRM.

Diabetes and tuberculosis: An emerging dual threat to healthcare.

Tuberculosis (TB) remains a huge global healthcare challenge even in the 21st century though the prevalence has dropped in developed countries in recent decades. Diabetes mellitus (DM) is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM. The coexistence of both diseases in the same individual also aggravates disease severity, complications, and chance of treatment failure because of gross immune alterations posed by DM as well as TB. Various complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and DM, some of which remain unknown even today. It is highly important to identify the risk factors for TB in patients with DM, and vice versa, to ensure early diagnosis and management to prevent complications from this ominous coexistence. In their research study published in the recent issue of the World Journal of Diabetes, Shi et al elaborate on the factors associated with the development of TB in a large cohort of DM patients from China. More such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

Complications and Mortality Rate of Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

OBJECTIVE: The goal of this study is to evaluate the complications and mortality associated with vagus nerve stimulation (VNS). METHODS: We retrospectively reviewed medical records of patients who underwent VNS implantation for the treatment of drug-resistant epilepsy (DRE) between 2000 and 2023. The mean follow-up time was 10.6 years, ranging from three months to 22 years. RESULTS: In total, 55 adult and pediatric patients received VNS therapy with 117 procedures performed over 23 years. The most common early complications were hoarseness and cough which were reported in eight adult patients (6.8%). Four children with intellectual disability (ID) had infection (3.4%), eight patients had lead breakage (6.8%), and two had device migration (1.7%). Four of all patients (7.3%) demonstrated late complications due to chronic nerve stimulation including vocal cord dysfunction, late-onset severe AV block, and obstructive sleep apnea (OSA). Three patients (5.5%) had VNS deactivated permanently due to complications and/or lack of efficacy. Two patients died from probable sudden unexpected death in epilepsy (SUDEP) with an incidence of 3.4/1000 person-years. CONCLUSIONS: VNS therapy is safe over long-term follow-up but not without risks. Most post-operative complications are minor and transient for adults. Children with ID tend to have infection and device migration. Late-onset cardiac complications and OSA can develop in some patients during VNS therapy and should not be overlooked. The SUDEP rate may decrease with VNS therapy over time.

Polypharmacy to Clozapine Monotherapy in Treatment-Resistant Schizophrenia: A Case Report and Review of the Literature.

This case report discusses a 25-year-old Middle Eastern female with a 14-year history of schizophrenia, managed as an inpatient for nearly eight years. Initially referred to a psychiatrist at age 12, with one-year-long concerns about preoccupation with the idea of having a serious illness, depressed mood, decreased appetite, social withdrawal, and aggression, she underwent multiple admissions, various medication combinations, and electroconvulsive therapy but remained resistant to treatment until clozapine monotherapy was initiated in 2023. After starting clozapine, improvements were noted in speech, communication, and eye contact, though negative symptoms and bouts of aggression persisted. This case highlights the efficacy of clozapine monotherapy in managing treatment-resistant schizophrenia after years of ineffective polypharmacy treatment. The importance of clozapine in treating treatment-resistant schizophrenia cannot be understated. Despite its efficacy, clozapine is often underutilised globally due to concerns about adverse effects and the need for blood monitoring, leading to the overuse of antipsychotic polypharmacy. This polypharmacy is associated with higher adverse event rates, increased costs, and uncertain long-term safety. This case report demonstrates the successful management of treatment-resistant schizophrenia with clozapine monotherapy. The patient's significant improvement supports the need to prioritise clozapine, highlighting its benefits over polypharmacy and advocating for its broader use to enhance patient outcomes.

A case of acute purulent pericarditis due to MRSA treated with daily pericardial lavage for one month followed by pericardial fenestration.

Acute purulent pericarditis is a rare infection in developed countries. We herein report a case with diabetic nephropathy under maintenance hemodialysis who suffered from acute purulent pericarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). The treatment of purulent pericarditis mainly involves rapid administration of appropriate antibiotics and drainage. However, in this case, the patient was unresponsive to vancomycin and performing early surgical intervention was challenging due to highly pathogenic MRSA. Therefore, we performed pericardial fenestration in the chronic phase to suppress the risk of fatal secondary infections after daily irrigation for one month to reduce bacterial load mechanically. Learning objective: In a case of purulent pericarditis caused by highly pathogenic methicillin-resistant Staphylococcus aureus resistant to antibiotics and resulting in constrictive pericarditis, it was possible to perform pericardial fenestration in the chronic phase, while mitigating the risk of fatal secondary infections, by controlling the inflammation through daily irrigation for a long time to reduce the bacterial load mechanically.

Silencing SPP1 in M2 macrophages inhibits the progression of castration-resistant prostate cancer via the MMP9/TGFß1 axis.

Background: M2 macrophages can promote the progression of castration-resistant prostate cancer (CRPC), but the specific mechanism is still unclear. Therefore, we are preliminarily exploring the molecular mechanism by which M2 macrophages regulate the progression of CRPC. Methods: The genes positively correlated with CRPC and with the most significant differences in the GEO32269 dataset were obtained. Database and immunofluorescence experiments were used to validate the localization of secreted phosphoprotein 1 (SPP1) in localized prostate cancer (PCa), hormone-sensitive prostate cancer (HSPC), and CRPC tumor tissues. The function of SPP1 in M2 macrophages was verified through cell scratch, Transwell, and an orthotopic PCa model. PCa database and Western blot were used to verify the relationship between SPP1 and matrix metallopeptidase 9 (MMP9), as well as the ability of MMP9 in M2 macrophages to promote epithelial-mesenchymal transition (EMT) in PCa cells. Results: The primary localization of SPP1 in prostate and CRPC tissues is in macrophages. Silencing SPP1 expression in M2 macrophages promotes their polarization towards the M1 phenotype and significantly inhibits the malignant progression of PCa in vitro and in vivo. SPP1 promotes the expression of MMP9 through the PI3K/AKT signaling pathway in M2 macrophages. Furthermore, MMP9 enhances the EMT and migratory capabilities of PC3 cells by activating the TGFß signaling pathway. Conclusions: We have found that the high expression of SPP1 in M2 macrophages promotes the progression of CRPC through cell-cell interactions. These findings can contribute to the development of novel therapeutic approaches for combating this deadly disease.

Development and validation of a prognostic nomogram to predict 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate.

Background: Carbapenem-resistant Gram-negative organism (CRO) infection is a critical clinical disease with high mortality rates. The 30-day mortality rate following antibiotic treatment serves as a benchmark for assessing the quality of care. Colistin sulfate is currently considered the last resort therapy against infections caused by CRO. Nevertheless, there is a scarcity of reliable tools for personalized prognosis of CRO infections. This study aimed to develop and validate a nomogram to predict the 30-day all-cause mortality in patients with CRO infection who underwent colistin sulfate treatment. Methods: A prediction model was developed and preliminarily validated using CRO-infected patients treated with colistin sulfate at Tongji Hospital in Wuhan, China, who were hospitalized between May 2018 and May 2023, forming the study cohort. Patients admitted to Xianning Central Hospital in Xianning, China, between May 2018 and May 2023 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of 30-day all-cause mortality. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and the calibration curve were used to evaluate model performance. The decision curve analysis (DCA) was used to assess the model clinical utility. Results: A total of 170 patients in the study cohort and 65 patients in the external validation cohort were included. Factors such as age, duration of combination therapy, nasogastric tube placement, history of previous surgery, presence of polymicrobial infections, and occurrence of septic shock were independently associated with 30-day all-cause mortality and were used to construct the nomogram. The AUC of the nomogram constructed from the above six factors was 0.888 in the training set. The Hosmer-Lemeshow test showed that the model was a good fit (p = 0.944). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram. Conclusion: A nomogram was developed and validated to predict the occurrence of 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate. This nomogram offers healthcare providers a precise and efficient means for early prediction, treatment management, and patient notification in cases of CRO infection treated with colistin sulfate.

Comprehensive lipidomic insights of differentially accumulating lipids in large pigmented rice sprout collection and the changes in the starch composition upon germination.

Germination represents a vital bioprocess characterized by numerous biochemical transformations that significantly influence the nutritional characteristics of rice. The mobilization of starch and lipids during germination plays a pivotal role in altering the dietary profile of rice, thus potentially addressing the nutritional requirements of populations heavily reliant on rice as a staple food. To explore this potential, a comprehensive analysis encompassing lipidomics and starch composition was conducted on a diverse collection of pigmented rice sprouts. High-resolution mass spectrometry unveiled substantial shifts in the lipidome of pigmented rice sprouts, showcasing a notable enrichment in carotenoids and unsaturated triglycerides, with potential human health benefits. Notably, purple rice sprouts exhibited heightened levels of alpha- and beta-carotene. Analysis of starch composition revealed slight changes in amylose and amylopectin content; however, a consistent increase in digestible carbohydrates was observed across all rice varieties. Germination also led to a reduction in resistant starch content, with purple rice sprouts demonstrating a pronounced two-fold decrease (p < 0.05). These changes were corroborated by a 1.33% decrease in gelatinization enthalpy and a 0.40% reduction in the melting of the amylose-lipid complex. Furthermore, pasting property analysis indicated a substantial 42% decrease in the complexation index post-germination. We posit that the insights garnered from this study hold significant promise for the development of novel products enriched with health-promoting lipids and characterized by unique flour properties.

New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer?

INTRODUCTION: Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD. AREAS COVERED: This paper reviews the literature on glutamate transmission in OCD. In addition, the authors examine the results of clinical trials investigating the efficacy of glutamatergic agents in the treatment of OCD patients. EXPERT OPINION: Along with the recognition of neuroinflammation in the brain in OCD, the evidence of glutamate dysfunction represents one of the most promising recent discoveries for understanding the mechanisms involved in OCD. The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients.

Impact of clozapine once-daily versus multiple-daily dosing regimen on relapse in patients with treatment-resistant schizophrenia: A 1-year retrospective cohort study.

RATIONALE: Clozapine, the standard treatment for treatment-resistant schizophrenia (TRS), is generally recommended in a multiple-daily dosing regimen. However, it is commonly administered once daily in clinical practice. Few studies have compared the longitudinal clinical outcomes of these two dosing regimens. OBJECTIVE: To investigate the effect of once-daily versus multiple-daily dosing regimens of clozapine on relapse in patients with TRS. METHODS: This retrospective cohort study included patients with TRS who commenced treatment with clozapine during hospitalization and were discharged between April 2012 and January 2022 from a tertiary psychiatric hospital in Japan. Relapse, defined as a psychiatric exacerbation requiring re-hospitalization within the first-year post-discharge, was analyzed. Multivariable Cox proportional hazards regression analysis compared the relapse risk between once-daily and multiple-daily dosing regimens. A subgroup analysis was conducted to examine the potential interactions between dosing regimen and dose category (low versus high dose). RESULTS: Among 179 patients, 107 (59.8%) received clozapine once daily. No significant difference in the relapse risk was observed between once-daily and multiple-daily dosing regimens (adjusted hazard ratio [aHR]: 1.16; 95% confidence interval [CI]: 0.68-1.99; p = 0.58). However, in patients receiving high doses of clozapine (> 300 mg/day), multiple-daily dosing increased the relapse risk compared to once-daily dosing (aHR: 2.23; 95% CI: 1.00-4.97; p = 0.049). CONCLUSIONS: Once-daily clozapine dosing may not be associated with an increased relapse risk. The increased relapse risk in high-dose multiple-daily dosing may be confounded by unmeasured non-adherence. Further randomized controlled trials are required to validate these findings.

Antibacterial activity evaluation of a novel K3-specific phage against Acinetobacter baumannii and evidence for receptor-binding domain transfer across morphologies.

Acinetobacter baumannii (A. baumannii) poses a serious public health challenge due to its notorious antimicrobial resistance, particularly carbapenem-resistant A. baumannii (CRAB). In this study, we isolated a virulent phage, named P1068, from medical wastewater capable of lysing CRAB, primarily targeting the K3 capsule type. Basic characterization showed that P1068 infected the A. baumannii ZWAb014 with an optimal MOI of 1, experienced a latent period of ten minutes and maintained stability over a temperature range of 4 °C to 37 °C and pH range of 3-10. Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses (ICTV). Additionally, according to classical morphological classification, P1068 is identified as a T4-like phage (Myoviridae). Interestingly, we found that the tail fibre protein (TFP) of P1068 shares 74% coverage and 88.99% identity with the TFP of a T7-like phage (Podoviridae), AbKT21phiIII (NC_048142.1). This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies. In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A. baumannii in both biofilm and planktonic states. In mouse models of intraperitoneal infection, P1068 phage protected mice from A. baumannii infection and significantly reduced bacterial loads in various tissues such as the brain, blood, lung, spleen, and liver compared to controls. In conclusion, this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilm-forming A. baumannii infections, and expands the understanding of horizontal transfer of phage TFP genes.

Development and initial evaluation of a clinical prediction model for risk of treatment resistance in first-episode psychosis: Schizophrenia Prediction of Resistance to Treatment (SPIRIT).

BACKGROUND: A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication. AIMS: To develop and evaluate a model that could predict the risk of TRS in routine clinical practice. METHOD: We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model. RESULTS: We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723-0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism. CONCLUSIONS: We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.

Identification of clusters of secondary metabolite biosynthetic genes in the Camelina sativa genome.

Multidrug-resistant pathogens pose an earnest risk to human health. Therefore, new antibiotics need to be developed quickly. Most of the antibiotics we use today are derived from secondary metabolites, which are produced by plants. Genome mining tools allow us to detect biosynthetic gene clusters (BGCs) responsible for the production of secondary metabolites. Focusing on the most promising BGCs-coding antibiotics with unique pathways is currently a challenge. In silico approach like genome mining are used to visualise the action of these bioactive chemicals. Camelina sativa is a well-known medicinal plant and it would be interesting to study its secondary metabolites. In this work, we found seven bioactive compounds in this plant using the genome mining approach. Further, the clusters of genes involved in the biosynthesis of these compounds were analysed with their metabolic pathways. This work illuminates new ground on the evolution of BGCs for the nutritional improvement of C. sativa.

Whole genome sequencing insight into carbapenem-resistant and multidrug-resistant Acinetobacter baumannii harboring chromosome-borne blaOXA-23.

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure "ISAba1-blaADC-25." The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.

Concentration of IL-1ß, IL-7, IL-12, IL-17, CX3CL1, ITAC and relation with the seizure severity and sudden unexpected death in epilepsy patient.

OBJECTIVE: Inflammation plays an important role in epilepsy. There is evidence for the relationship between proinflammatory cytokines and epilepsy. We aimed to detect the serum levels of multiple cytokines in epilepsy patients, looking for biological indicators, and providing a theoretical basis for the clinical diagnosis, treatment, and prognosis of epilepsy. MATERIALS AND METHODS: In this study, 30 patients with drug-resistant epilepsy (DRE), 30 patients with well-controlled epilepsy (WCE), and 29 healthy controls (HC) were enrolled. Multi-proinflammatory cytokines were measured by LUMINX multi-factor detection. RESULTS: The levels of IL-1ß, IL-7, IL-12, and IL-17 were significantly elevated, and the levels of CX3CL1 and ITAC were significantly decreased in epilepsy patients compared with healthy controls. Furthermore, the level of IL-17 was significantly higher in the DRE group compared to WCE. We also found the ratio of IL-7/CX3CL discriminates accurately between patients and controls, with a ROC Area Under the Curve (AUC) of 0.963 (P<0.001). The levels of IL-1ß, IL-7, IL-12, and IL-17 in the DRE group were positively correlated with the National Hospital Seizure Severity Scale (NHS3) scores (IL-1ß, P = 0.029; IL-12, P = 0.039; IL-17, P = 0.004). IL-17 was positively correlated with seizure frequency (P = 0.050), while ITAC was negatively correlated with seizure frequency (P = 0.012) and Sudden Unexpected Death in Epilepsy-3 (SUDEP-3) scores (P = 0.023). CONCLUSIONS: IL-1ß, IL-12, and IL-17 may be used to predict seizure severity and the IL-7/CX3CL1 ratio may be a candidate biomarker for predicting epileptic seizures. While CX3CL1 and ITAC play anti-epileptic effects, ITAC may be used to assess the risk of SUDEP.

New resorcylic acid derivatives of Lysimachia tengyuehensis against MRSA and VRE by interfering with bacterial metabolic imbalance.

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.

Mediastinitis caused by an NDM-1 Escherichia coli in a child with Dacron® Sano shunt after pulmonary atresia with ventricular septal defect surgery treated with combination of aztreonam-avibactam.

Carbapenem-resistant Enterobacterales are being increasingly reported and cause nosocomial infections, which may include post-operative mediastinitis. Here, we report a post-operative mediastinitis caused by an Escherichia coli NDM-1 carbapenemase producer in a 13-month boy with DiGeorge syndrome. The infection was managed with surgical debridement and antibiotherapy with aztreonam, ceftazidime-avibactam and IV fosfomycin for 6 weeks. The evolution was favorable without relapse with 10 weeks of follow-up.

Outcome of extracorporeal membrane oxygenation support among children with methicillin-resistant Staphylococcus aureus infection: A single-center experience.

Introduction: The use of extracorporeal membrane oxygenation (ECMO) in children continues to increase nationally, including patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Survival of pediatric patients with MRSA sepsis has not improved over the last 20 years. We sought to review our institutional experience and outcomes of ECMO support among children with MRSA infection.Methods: Children aged 0-19 years who received ECMO support from October 2014 to June 2021 were reviewed retrospectively. Patients with laboratory confirmed MRSA infections were identified.Results: Out of 88 unique pediatric patients requiring ECMO support, eight patients had documented MRSA infections. The duration of mechanical ventilation prior to ECMO initiation was an average of seven days (range 0.7 to 21.8 days). The median ECMO duration was 648.1 h (range 15.5 to 1580.5 h). Five patients were successfully decannulated; however, only two patients survived to discharge. The two surviving patients were both cannulated via VV-ECMO. Mechanical ventilation prior to ECMO was 4.5 and 21.8 days in these cases with run durations of 18.9 and 29.9 days, respectively.Conclusions: Our institutional survival of patients with MRSA on ECMO is lower than what has been reported in recent database studies, but notably, 62.5% were successfully decannulated. While both surviving patients were supported with VV-ECMO, there was no other clear trend in factors that contributed to survival. MRSA continues to be a source of significant morbidity and mortality among pediatric patients. On-going investigation of outcomes and factors contributing to survival in patients with MRSA infection on ECMO is warranted.