Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides.

HYPOTHESIS: Although antimicrobial peptides (AMPs) are a promising class of new antibiotics, their inherent susceptibility to degradation requires nanocarrier-mediated delivery. While cubosome nanocarriers have been extensively studied for delivery of AMPs, we do not currently understand why cubosome encapsulation improves antimicrobial efficacy for some compounds but not others. This study therefore aims to investigate the link between the mechanism of action and permeation efficiency of the peptides, their encapsulation efficacy, and the antimicrobial activity of these systems. EXPERIMENTS: Encapsulation and delivery of Indolicidin, and its ultra-short derivative, Priscilicidin, were investigated using SAXS, cryo-TEM and circular dichroism. Molecular dynamics simulations were used to understand the loading of these peptides within cubosomes. The antimicrobial efficacy was assessed against gram-negative (E. coli) and gram-positive (MRSA) bacteria. FINDINGS: A high ionic strength solution was required to facilitate high loading of the cationic AMPs, with bilayer encapsulation driven by tryptophan and Fmoc moieties. Cubosome encapsulation did not improve the antimicrobial efficacy of the AMPs consistent with their high permeation, as explained by a recent 'diffusion to capture model'. This suggests that cubosome encapsulation may not be an effective strategy for all antimicrobial compounds, paving the way for improved selection of nanocarriers for AMPs, and other antimicrobial compounds.

Efficacy of Probiotics as Adjuvant to the Standard Triple Therapy for the Treatment of Helicobacter Pylori-Associated Peptic Ulcer Disease: A Randomized-Control Trial.

Helicobacter pylori (H. pylori) is a major cause of peptic ulcer disease (PUD), which needs effective eradication of the organism to heal ulcers and prevent a recurrence. In recent years, increasing resistance of H. pylori to clarithromycin and amoxicillin have decreased peptic ulcer cure rate following treatment with standard triple therapy worldwide. The addition of probiotics with standard triple therapy has shown excellent efficacy in H. pylori eradication and has appeared to be an alternative treatment strategy. This study aimed to assess the efficacy of standard triple therapy plus probiotics for H. pylori eradication and ulcer healing compared to standard triple therapy alone. This double-blind, randomized placebo-controlled clinical trial included 158 with endoscopically proven H. pylori-positive PUD who were randomly allocated equally into two groups; Group A was treated with standard triple therapy plus probiotics, and Group B was treated with standard triple therapy plus placebo for 14 days. The outcome was evaluated at the end of treatment (14th day) (symptoms plus adverse events) and after 60 days of treatment completion (H. pylori eradication and ulcer healing). One hundred forty four (144) study subjects (73 in Group A and 71 in Group B) completed the study. Significantly higher H. pylori eradication rate (82.2%vs. 67.6%, p=0.043) and ulcer healing rate (92.3% vs. 60.0%, p=0.049) were observed in the standard triple therapy plus probiotic group than the standard triple therapy plus placebo group. Early relief of epigastric pain was also seen among patients getting probiotics than the placebo in addition to standard triple therapy (42.3% vs. 15.1%, p<0.001).The addition of probiotics significantly improves the H. pylori eradication rate and ulcer healing rate among the patients getting standard triple therapy. Further large-scale, multi-center studies are needed to recommend routine use of probiotics with standard triple therapy for H. pylori eradication.

A Consensus on Staphylococcus aureus Exacerbated Atopic Dermatitis and the Need for a Novel Treatment.

The skin microbiome is essential for skin barrier function because it inhibits pathogen colonization, and decreased microbiome diversity correlates with increased Staphylococcus aureus (S. aureus) burden and atopic dermatitis (AD) severity. Managing S. aureuss-driven AD in clinical practice remains problematic due to complications such as AD exacerbation, impetigo, abscesses, and invasive infections. This project used a modified Delphi process comprising face-to-face discussions followed by a blinded vote to define 5 final consensus statements. A panel of 6 pediatric dermatologists developed a consensus on S. aureus-driven AD exacerbation, challenges in current treatments for AD with secondary bacterial infections, and new developments to improve patient care and outcomes. The panel's 5 consensus statements provide recommendations for dermatologists, pediatricians, and healthcare providers treating patients with secondary infected AD. These recommendations underscore the importance of recognizing and managing S. aureus skin infection in AD clinical practice and promoting antibiotic stewardship to mitigate resistance. The panel defined a significant unmet need for a single topical AD therapy effective against all symptoms, including pruritus, S. aureus-driven AD exacerbation, infection, and inflammation, across AD severity levels. J Drugs Dermatol. 2024;23(10):825-832. doi:10.36849/JDD.8240.

Profile of antimicrobial use and potential use of the defined daily dose in neonatology.

One of the measures for monitoring microbial resistance is the calculation of the defined daily dose of antimicrobial agents. For this calculation, the weight of an adult of 70 kg is used as a standard, so that application in neonatology is not possible. The aim of this study is to describe the use profile and calculate the defined daily dose (DDD) of antimicrobials in a neonatal intensive care unit (NICU) of a public hospital in the interior of Bahia, Brazil. From March 2020 to December 2021, the medical records of 712 newborns admitted to a NICU between September 2018 and June 2020 were analyzed. A total of 410 newborns diagnosed with neonatal sepsis were included. The most used antimicrobials per patient were gentamicin (408/410; 99.5%), ampicillin (407; 99.3%), amikacin (29; 7.1%) and oxacillin (21; 5.1%), with a mean (SD) treatment duration of 9.8 (3.9) days. The most commonly used combination of antimicrobials was ampicillin with gentamicin, which was used in 406 patients (99.0%). The values for neonatal DDDs were on average 26 times lower than those for adult DDDs. The neonatal DDDs were similar to those observed in other studies. Ampicilin and cefepime were the antimicrobials for which the greatest differences were observed in neonatal DDDs compared with adult DDDs, which differed mainly between maintenance doses, reflecting the lack of international standards in neonatology. Standardization of DDDs as a surveillance measure has the potential to clarify the pattern of antimicrobial use in neonatal patients worldwide and, in particular, to prevent indiscriminate use and bacterial resistance.

Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment.

BACKGROUND: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. METHODS: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. RESULTS: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. CONCLUSIONS: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients.

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400. DESIGN: Prospective population pharmacokinetic study of vancomycin. SETTING: Critically ill patients in quaternary care PICUs. PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children's Hospital and Texas Children's Hospital were enrolled. INTERVENTIONS: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. MEASUREMENTS AND MAIN RESULTS: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6-10.0 µg/mL when MIC = 1 µg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. CONCLUSIONS: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.

Oral delivery of Sunitinib malate using carboxymethyl cellulose/poly(acrylic acid-itaconic acid)/Cloisite 30B nanocomposite hydrogel as a pH-responsive carrier.

This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.

Sepsis surveillance in patients with head-and-neck cancer undergoing chemo-radiation.

BACKGROUND: The infection rate among patients with head-and-neck cancer (HNC) undergoing chemoradiotherapy (CRT) is approximately 19%, with sepsis-related death ranging from 3-9%. A previous study at our institute found a 12% sepsis-related death rate in HNC patients during CRT. The objective of this study is to investigate the utilization of sepsis surveillance and early intervention in reducing the occurrence of sepsis-related deaths in locally advanced HNC patients receiving CRT. METHODS: This retrospective analysis examined 54 patients with locally advanced HNC undergoing CRT who underwent sepsis surveillance between January 2018 and December 2021. The study recorded the utilization of oral and intravenous antibiotics, G-CSF, early admissions and their reasons, and the incidence of early mortality. Data analysis was conducted using SPSS v.24 software. RESULTS: Twenty-one (38.9%) patients were prescribed oral antibiotics, and 14 (25.9%) received G-CSF on an outpatient basis. Twenty-nine (54%) patients required hospital admission. Among the admitted patients, 28 (96%) received intravenous antibiotics, and G-CSF was administered in 18 (62%) patients. In 8 cases, antibiotic treatment was intensified due to persistent fever and deteriorating neutropenia. The median time for receiving antibiotics and G-CSF after starting CRT was 5th week (range: 3-8 weeks). Five patients required readmission. Only one patient succumbed to sepsis. Among the 54 patients, 48 (89%) completed the scheduled RT, while 14 (25.9%) received all 6 cycles of chemotherapy. CONCLUSION: Sepsis surveillance and the prompt use of antibiotics and G-CSF, along with early hospitalization, when necessary, reduces the occurrence of sepsis-related early deaths in HNC patients undergoing CRT.

Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment.

Purpose: The purpose of this work was to understand the impact of melanin binding on ocular pharmacokinetics after administration of a high-binder model drug via different administration routes. Methods: We applied levofloxacin to pigmented and albino rabbits as eye drops (single and multiple), as well as by intravitreal and intravenous injections. Ocular tissues and plasma were analyzed for levofloxacin concentrations with liquid chromatography-mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated. Results: The data show enrichment of levofloxacin and weeks-long retention in pigmented tissues. Upon intravitreal injection, the area under the curve (AUC) values in pigmented tissues were about 9 to 15 times higher than the respective values in the albino rabbits, but this difference expanded to 255- to 951-fold following topical eye drop administration. Multiple dosing of eye drops led to substantial accumulation of levofloxacin in the pigmented tissues: AUC values were 3 to 12 times higher than after intravitreal injection. The AUCs were much lower after single topical or intravenous drug administrations. High drug levels (0.1-35 µM) were always observed in the neural retinas of pigmented eyes; the highest exposure was seen after intravitreal administration followed by multiple doses of topical drops. Single topical instillation and intravenous injections to the albino rabbits resulted in vitreal bioavailability values of 0.009% and 0.003%, respectively. Conclusions: Melanin binding can be used to achieve targeted drug delivery and extended retention in pigmented ocular tissues. The results from topical multiple dosing experiments suggest that eye drop treatment may yield drug exposures and responses comparable to intravitreal delivery, even in the retinal pigment epithelium and choroid.

A multicentric, randomized, controlled clinical trial to study the impact of bedside model-informed precision dosing of vancomycin in critically ill children-BENEFICIAL trial.

BACKGROUND: Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. METHODS: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. DISCUSSION: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. TRIAL REGISTRATION: Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.

Comparison of Short-Term Therapeutic Effects between Amoxicillin-Clavulanic Acid and Ceftriaxone Sodium on Febrile Urinary Tract Infections in Children under Five Years Old.

BACKGROUND: Febrile urinary tract infections in children are typically treated with a standard 10-day course of antibiotics. However, prolonged antibiotic use can lead to increased bacterial resistance, underscoring the need to explore shorter treatment regimens. This study aimed to compare the short-term therapeutic effects of amoxicillin-clavulanic acid and ceftriaxone sodium in children under five years old with febrile urinary tract infections. METHODS: Clinical data from 109 children under five years old diagnosed with febrile urinary tract infections between August 2022 and December 2023 were retrospectively analyzed. Among them, 52 children received ceftriaxone sodium (group A), and 48 children received amoxicillin-clavulanic acid (group B). Clinical symptoms, laboratory indicators, clinical efficacy, and adverse reactions were compared between the two groups. RESULTS: Children from group B showed significantly shorter improvement times for fever, dysuria, and urinary frequency compared to those in group A (p < 0.05). Initially, there were no significant differences in the levels of white blood cell counts, squamous epithelial cells, bacteria, interleukin-6, interleukin-8, and neutrophil gelatinase-associated lipocalin between the two groups (p > 0.05). However, after treatment, group B exhibited significantly lower levels of white blood cell counts, squamous epithelial cells, bacteria, interleukin-6, interleukin-8, and neutrophil gelatinase-associated lipocalin compared to group A (p < 0.05). Moreover, the total effective rate was significantly higher in group B (95.83%) than in group A (80.77%) (p < 0.05). There was no significant difference in the incidence of adverse reactions between groups B (10.42%) and A (13.45%) (p > 0.05). CONCLUSIONS: Amoxicillin-clavulanic acid demonstrated superior short-term therapeutic efficacy for febrile urinary tract infections in children under five years old compared to ceftriaxone sodium. It effectively reduced cure times, mitigated inflammatory responses, and improved treatment outcomes, suggesting its potential for broader clinical application and adoption.

[Medical and surgical treatment of parapneumonic effusion]. / Traitement médical et chirurgical de l'épanchement parapneumonique.

Pleural empyema, defined as the presence of pus in the pleural space, is a serious complication of pleural effusion. Overall incidence of pleural infection is increasing particularly in the elderly. The outcome of this serious condition depends on prompt evaluation and therapeutic intervention. The management comprises antibiotic therapy, evacuation of the effusion with different options and physical therapy. This article defines the natural history of complicated pleural effusion and reviews the range of therapeutic tools in adults whose choice is guided by individual factors.

L'empyème pleural, défini par la présence de microorganismes dans l'espace pleural, est une complication grave d'un épanchement pleural, dont l'incidence est rapportée en progression au cours des dernières décennies, notamment chez la personne âgée. L'issue de cette pathologie dépend de la rapidité du diagnostic et du choix adéquat des options thérapeutiques. La prise en charge une fois le diagnostic établi comprend l'antibiothérapie, l'évacuation de l'épanchement incluant différentes stratégies et la physiothérapie. Cet article décrit l'histoire naturelle de l'épanchement pleural compliqué et résume l'éventail des outils thérapeutiques chez l'adulte dont le choix demeure guidé par les facteurs individuels.

[Neoehrlichiosis : rare tick-borne disease, also present in Switzerland]. / Neoehrlichiose : maladie rare transmise par les tiques, aussi en Suisse.

For several years, there has been increasing awareness of a novel tick-borne infection within our region: neoehrlichiosis. The causative agent, Neoehrlichia mikurensis , is an intracellular bacterium classified within the Anaplasmataceae family. Predominantly afflicting immunosuppressed individuals, its clinical presentation often involves persistent fever accompanied by vascular complications. Diagnostic protocols typically entail targeted PCR testing of blood specimens, often leading to diagnostic delays. Timely initiation of doxycycline therapy typically ensures prompt resolution of symptoms.

Depuis quelques années, nous observons une nouvelle infection, transmise par les tiques dans notre pays, la neoehrlichiose. Neoehrlichia mikurensis, la bactérie responsable de cette maladie est intracellulaire et fait partie des Anaplasmataceae. La maladie touche surtout les personnes immunosupprimées et se manifeste par une fièvre persistante et des atteintes vasculaires. Le diagnostic repose sur la recherche de la bactérie par une PCR spécifique dans le sang, ce qui explique le délai souvent conséquent avant le diagnostic. Un traitement par doxycycline permet une guérison rapide.

A Case of Streptococcus iniae Pyocephalus, Subdural Empyema, and Diffuse Leptomeningitis in an Elderly Male: A Case Report.

We present a case of Streptococcus iniae causing leptomeningitis, pyocephalus, and subdural empyema in an elderly male from India. There have been only a handful of cases of S. iniae infection reported worldwide, and none of them have been from India. In this case, an elderly diabetic patient presenting with backache, headache, and fever with severe neurological worsening was diagnosed with severe invasive S. iniae infection. He had hydrocephalus that needed ventriculoperitoneal shunting. The patient was treated with a prolonged course of intravenous ampicillin and vancomycin.

Sensorineural hearing loss in Lyme neuroborreliosis.

BACKGROUND: Sensorineural hearing loss (SNHL) has been suggested to occur in patients with Lyme neuroborreliosis (LNB); however, a clear association has never been documented. The present study prospectively investigated the development of SNHL in patients admitted for treatment of LNB using distortion-product-oto-acoustic emissions (DPOAE) as a measure of cochlear function. METHODS: DOAE were measured in patients with LNB on the day of diagnosis, during treatment, and 30-60 days after discharge. Frequencies were categorized as Low (1, 1.5, 2 kHz), Mid (3, 4, 5 kHz), Mid-high (6, 7, 8 kHz), and High (9, 10 kHz). Pure Tone Audiometry (PTA3) was performed at discharge and 60 days after. Patients were treated with i.v. ceftriaxone or oral doxycycline for 14 days according to guidelines. RESULTS: DPOAE measurements were obtained in 25 patients with LNB at admission and in 18 patients at follow-up. Median age was 56 years (IQR, 48-64 years), and 16 (67%) were men. Fourteen (78%) of 18 patients showed improvement in Emission Threshold Levels (ETL) from admission to follow-up in low, mid-, and mid-high frequency categories, where ETLs increased by median levels of 3.2 (-4.1 to 8.3), 7.5 (-2.8 to 9.8), and 4.7 dB (-4.3 to 10.1). A decline was observed in the high frequency category, median -3.3 dB (-9.1 to 6.7). SNHL defined by pure tone average (PTA3) >20 dB was present in 11 out of 23 (48%) at discharge and in 9 out of 16 patients (56%) 60 days after discharge, which differed significantly from matched controls (Mann-Whitney test, p = 0.036). CONCLUSION: LNB can lead to cochlear outer-hair cell dysfunction, resulting in temporary and long-term SNHL.

Development and Validation of a Machine Learning Model for Early Detection of Untreated Infection.

BACKGROUND: Early diagnostic uncertainty for infection causes delays in antibiotic administration in infected patients and unnecessary antibiotic administration in noninfected patients. OBJECTIVE: To develop a machine learning model for the early detection of untreated infection (eDENTIFI), with the presence of infection determined by clinician chart review. DERIVATION COHORT: Three thousand three hundred fifty-seven adult patients hospitalized between 2006 and 2018 at two health systems in Illinois, United States. VALIDATION COHORT: We validated in 1632 patients in a third Illinois health system using area under the receiver operating characteristic curve (AUC). PREDICTION MODEL: Using a longitudinal discrete-time format, we trained a gradient boosted machine model to predict untreated infection in the next 6 hours using routinely available patient demographics, vital signs, and laboratory results. RESULTS: eDENTIFI had an AUC of 0.80 (95% CI, 0.79-0.81) in the validation cohort and outperformed the systemic inflammatory response syndrome criteria with an AUC of 0.64 (95% CI, 0.64-0.65; p < 0.001). The most important features were body mass index, age, temperature, and heart rate. Using a threshold with a 47.6% sensitivity, eDENTIFI detected infection a median 2.0 hours (interquartile range, 0.9-5.2 hr) before antimicrobial administration, with a negative predictive value of 93.6%. Antibiotic administration guided by eDENTIFI could have decreased unnecessary IV antibiotic administration in noninfected patients by 10.8% absolute or 46.4% relative percentage points compared with clinicians. CONCLUSION: eDENTIFI could both decrease the time to antimicrobial administration in infected patients and unnecessary antibiotic administration in noninfected patients. Further prospective validation is needed.

Concentration-Dependent Effects of MXene Nanocomposite-Loaded Carboxymethyl Cellulose on Wound Healing.

Nanoparticles (NPs) have emerged as a promising solution for many biomedical applications. Although not all particles have antimicrobial or regenerative properties, certain NPs show promise in enhancing wound healing by promoting tissue regeneration, reducing inflammation, and preventing infection. Integrating various NPs can further enhance these effects. Herein, the zinc oxide (ZnO)-MXene-Ag nanocomposite was prepared, and the conjugation of its three components was confirmed through scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) mapping analysis. In vitro analysis using the agar well diffusion technique demonstrated that ZnO-MXene-Ag nanocomposite exhibited high antimicrobial efficacy, significantly inhibiting Escherichia coli, Salmonella, and Candida albicans, and showing enhanced potency when combined with tetracycline, resulting in a 2.6-fold increase against Staphylococcus and a 2.4-fold increase against Pseudomonas. The efficacy of nanocomposite-loaded carboxymethyl cellulose (CMC) gel on wound healing was investigated using varying concentrations (0, 1, 5, and 10 mg/mL). Wound healing was monitored over 21 days, with results indicating that wounds treated with 1 mg/mL ZnO-MXene-Ag gel exhibited superior healing compared to the control group (0 mg/mL), with significant improvements noted from Day 3 onward. Conversely, higher concentrations (10 mg/mL) resulted in reduced healing efficiency, particularly notable on Day 15. In conclusion, the ZnO-MXene-Ag nanocomposite-loaded CMC gel is a promising agent for enhanced wound healing and antimicrobial applications. These findings highlight the importance of optimizing NP concentration to maximize therapeutic benefits while minimizing potential cytotoxicity.

Postoperative recovery in peroral versus intravenous antibiotic treatment following laparoscopic appendectomy for complicated appendicitis: a substudy of a cluster randomized cluster crossover non-inferiority study.

BACKGROUND: Acute appendicitis is the most common cause of abdominal pain requiring surgery, usually managed with laparoscopic appendectomy. In Denmark, the standard postoperative treatment for complicated cases involves intravenous antibiotics. This study compares peroral versus intravenous antibiotics in the context of fast-track surgery and Enhanced Recovery After Surgery (ERAS) protocols. Our objective is to evaluate the impact of peroral versus intravenous antibiotics on patient-reported outcomes following laparoscopic appendectomy for complicated appendicitis. METHODS: This was a sub-study within a broader Danish cluster-randomized non-inferiority trial conducted at Zealand University Hospital, focusing on adult patients undergoing laparoscopic appendectomy for complicated appendicitis. Participants were randomized into two groups: one receiving a three-day course of peroral antibiotics and the other intravenous antibiotics after surgery. Recovery quality was assessed on the third postoperative day using the Quality of Recovery-15 (QoR-15) questionnaire. RESULTS: The study included 54 patients, 23 in the peroral and 31 in the intravenous groups. The peroral group reported significantly better recovery outcomes, with higher QoR-15 scores (mean difference of 12 points, p < 0.001). They also experienced shorter hospital stays, averaging 47 h less than the intravenous group (p < 0.001). No significant differences between the groups were observed in readmissions or severe postoperative complications. CONCLUSIONS: Peroral antibiotic administration after laparoscopic appendectomy for complicated appendicitis significantly improves patient recovery and reduces hospital stay compared to intravenous antibiotics. These results advocate a potential shift towards peroral antibiotic use in postoperative care, aligning with ERAS principles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04803422.

Effect of low vs. high vancomycin trough level on the clinical outcomes of adult patients with sepsis or gram-positive bacterial infections: a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. METHOD: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. RESULTS: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]. CONCLUSION: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections.