Multiresistant Pathogens Research Articles

Multi-resistant pathogens - are they also resistant to disinfectants?

Epidemiological studies show that the care of patients in rooms with a previous stay by a person with evidence of multi-resistant pathogens (MRP) is associated with an increased risk of these pathogens occurring. The question therefore regularly arises as to whether MRP also exhibit resistance to the disinfectants used. To date, there are no standardised definitions for "resistance" to disinfectants. However, disinfectants authorised on the market are also effective against multi-resistant pathogens and the failure of efficient disinfection is mainly caused by application errors (insufficient cleaning, incomplete wetting, incorrect application concentration or exposure time etc.). The effectiveness of disinfectants depends on a variety of environmental factors (especially accompanying contamination). A reduced sensitivity to disinfectants can occur in individual isolates due to selection under sub-inhibitory concentrations of disinfectants. Resistance mechanisms to antibiotics do not mediate cross-resistance to disinfectants, but a change in the permeability of bacterial cells can influence sensitivity to disinfectants and antibiotics. In general, the success of routine disinfection can be improved by suitable process controls and contribute to reducing the transmission of MRP.

Antibiotic Prophylaxis During Allogeneic Stem Cell transplantation—A Comprehensive Single Center Retrospective Analysis

BackgroundProphylactic antibiotics are still controversial during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our transplant center, we suspended antibiotic prophylaxis during allo-HSCT in 2017. ObjectiveThe main objective of this study was the detailed analysis of the potentially beneficial impact of omittance of standard antibiotic prophylaxis during allo-HSCT in survival and Graft-versus-Host disease (GvHD) development, especially with consideration of confounding factors and competing events. Secondary objectives were the evaluation of the risk of severe infections and transplant-related mortality without antibiotic prophylaxis, the detailed assessment of bacterial and viral infections including multiresistant pathogens as well as occurrence of relapse in both groups. This study aims to support the development of future antibiotic strategies in allo-HSCT. Study DesignWe retrospectively analyzed patient outcome in the time periods before (between December 2012 and February 2017) and after suspension (between March 2017 and June 2020) of antibiotic prophylaxis during allo-HSCT. Relevant clinical outcome parameters of the patients (n = 221) were collected by chart-review in the two groups (with antibiotic prophylaxis n = 101 versus without antibiotic prophylaxis n = 120). All patients were 18 years or older. Propensity score methods were used to adjust for potentially confounding patient characteristics. To address competing events, transitions between moderate/severe acute and chronic GvHD, relapse and death were analyzed using an inverse-propensity score weighted multistate modeling approach. ResultsWhile we observed a trend towards an improved outcome in the cohort without antibiotic prophylaxis, the inverse-propensity-score-weighted analyses did not show significant differences between the two groups in overall survival (OS) (P = .811) or development of acute GvHD (aGvHD) grade 3/4 (P = .158) and chronic moderate/severe GvHD (cGvHD) (P = .686). Multistate analysis respecting competing events revealed comparable estimated probabilities without antibiotic prophylaxis versus with antibiotic prophylaxis in OS (35.0% [95% CI: 28.2%-42.7%] versus 35.3% [95% CI: 27.8%-41.1%]) as well as development of aGvHD grade 3/4 (7.7% [95% CI: 5.9%-12.2%] vs. 10.6% [95% CI: 7.7%-15.7%]) and moderate/severe cGvHD (21.0% [95% CI: 17.7%-30.0%] vs. 23.8% [95% CI: 19.6%-31.4%]). Similar analyses showed also no significant differences in relapse rate, transplant-related mortality, relapse-related mortality, or GvHD-free/relapse-free survival between the two groups. An observed increase in severe infections without antibiotic prophylaxis did not lead to a significantly higher mortality rate. Viral reactivation and detection of multiresistant bacteria were comparable, yet a higher incidence of Clostridioides difficile infections was observed in patients receiving antibiotic prophylaxis. ConclusionOur study supports previous reports of noninferiority of allo-HSCT without use of antibiotic prophylaxis with close monitoring and rapid intervention, if infection is suspected. The trend towards improved outcomes without antibiotic prophylaxis, however, might not only be due to the absence of antibiotic prophylaxis but also due to additional progresses in the field over the recent years. While the present study is too small to draw definite conclusions, these results strongly warrant further multicenter studies addressing the potential benefit of omitting antibiotic prophylaxis during allo-HSCT.

The Successful Treatment of Multi-Resistant Colonized Burns with Large-Area Atmospheric Cold Plasma Therapy and Dermis Substitute Matrix—A Case Report

The treatment of severe burn injuries, which occur particularly in the context of armed conflicts, is based on a multimodal treatment concept. In addition to complex intensive care therapy, the surgical reconstruction options of plastic surgery and typical antiseptic wound treatment are the main focuses. In recent years, atmospheric cold plasma therapy (ACPT) has also become established for topical, antiseptic wound treatment and for the optimization of re-epithelialization. This case report shows a successful treatment of extensive burn injuries using dermal skin substitute matrix and topical treatment with a large-area cold plasma device to control multi-resistant pathogen colonization. This case report illustrates the importance of ACPT in burn surgery. However, larger case series and randomized controlled trials in specialized centers are needed to assess its place in future clinical practice.

In Vitro Safety Study on the Use of Cold Atmospheric Plasma in the Upper Respiratory Tract.

Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species, have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract (URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surface-microdischarge-based plasma intensive care (PIC) device was developed by terraplasma medical GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization of human oral keratinocytes (hOK), human bronchial-tracheal epithelial cells (hBTE), and human lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the "throat" and "subglottis" positions in the URT model did not show any significant differences from the untreated control (ctrl.) and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis, DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with the PIC device does not cause any cell damage. The extent to which immune cell activation is induced and whether it has long-term effects on the organism need to be carefully examined in follow-up studies in vivo.

The Effect of pH Variation on Antibiotic Susceptibility of MDR <i>Klebsiella pneumoniae</i> Isolates

Background: Klebsiella pneumoniae is a significant opportunistic pathogen responsible for various nosocomial infections in humans. The emergence of multi-drug resistant strains poses a significant challenge in clinical settings, necessitating a deeper understanding of factors influencing antimicrobial resistance. Objective: This research aimed to investigate the impact of pH variation on the resistance patterns of multi-resistant K. pneumoniae isolated from Iraqi patients with urinary tract infections and wound infections against different antibiotics. Methods: Forty K. pneumoniae isolates were obtained from urine samples and wound swabs, and their identification was confirmed using the VITEK ® 2 compact system and molecular identification of the rpoB housekeeping gene. Antibiotic susceptibility testing was performed using the Kirby Bauer’s disk diffusion method under varying pH conditions (pH 5, 7, 9, and 11) at 37°C for 18 to 24 hours. Results: The study findings indicated that K. pneumoniae isolates exhibited differential susceptibility to antibiotics based on pH conditions. Cefotaxime demonstrated increased efficacy under alkaline pH, while tetracycline showed optimal efficacy under acidic conditions. However, ciprofloxacin displayed resistant phenotypes at acidic pH 5 and either resistant or intermediate phenotypes at alkaline pH 9. Conclusions: The results suggest a potential influence of pH on the antibiotic susceptibility profiles of K. pneumoniae isolates. Understanding the role of pH in antimicrobial resistance can inform strategies for better managing infections caused by multi-resistant pathogens. Further research is warranted to elucidate the underlying mechanisms and implications for clinical practice.

Fourier Transform Infrared Spectroscopy Application for Candida auris Outbreak Typing in a Referral Intensive Care Unit: Phylogenetic Analysis and Clustering Cut-Off Definition.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and is able to persist for a long time on human skin and hospital environments. It is a critical issue on the WHO fungal priority list and therefore it is fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The purpose of this study was to apply Fourier transform infrared spectroscopy (FT-IR) to investigate the phylogenetic relationships among isolated strains from a C. auris outbreak at the University Intensive Care Unit of a Tertiary University hospital in Turin (Italy). To calculate a clustering cut-off, intra- and inter-isolate, distance values were analysed. The data showed the presence of a major Alfa cluster and a minor Beta cluster with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analyses. The application of FT-IR technology allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a "not WGS-based" clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for the rapid and cost-saving typing of C. auris strains with important clinical implications.

Modeling Host-Pathogen Interactions in C. elegans: Lessons Learned from Pseudomonas aeruginosa Infection.

Infections, such as that by the multiresistant opportunistic bacterial pathogen Pseudomonas aeruginosa, may pose a serious health risk, especially on vulnerable patient populations. The nematode Caenorhabditis elegans provides a simple organismal model to investigate both pathogenic mechanisms and the emerging role of innate immunity in host protection. Here, we review the virulence and infection strategies of P. aeruginosa and host defenses of C. elegans. We summarize the recognition mechanisms of patterns of pathogenesis, including novel pathogen-associated molecular patterns and surveillance immunity of translation, mitochondria, and lysosome-related organelles. We also review the regulation of antimicrobial and behavioral defenses by the worm's neuroendocrine system. We focus on how discoveries in this rich field align with well-characterized evolutionary conserved protective pathways, as well as on potential crossovers to human pathogenesis and innate immune responses.

Glycine restores the sensitivity to antibiotics in multidrug-resistant bacteria.

The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest non-essential amino acid in humans. Glycine is very effective in improving health and supporting growth and wellbeing of humans and animals. Instead, for many bacteria, high concentrations of glycine induce lysis or deep morphological alterations. The effect of glycine on multidrug resistant (MDR) microorganisms has not yet been extensively researched. The present study was conducted 1) to establish the effect of glycine on different nosocomial pathogens isolated during routine diagnostic investigations; 2) to determine the minimum inhibitory concentration of glycine and the type of activity performed (bacteriostatic or bactericidal) on representative isolates; 3) to test the interaction between glycine and meropenem, cefiderocol, or colistin. The data reported here show a dose-dependent activity of glycine on bacteria and its bactericidal activity on MDR bacteria. Furthermore, we found that the action of glycine restores in vitro the susceptibility of multiresistant nosocomial pathogens to the tested antibiotics.IMPORTANCEAntimicrobial resistance is a constantly growing concern throughout the world, and Italy is among the Western countries where antimicrobial resistance is most widespread. In Tuscany, carbapenemase-producing Enterobacterales are now even endemic. In this study, we challenged some resistant bacteria with a well-known molecule, glycine, the antibacterial properties of which have been known since the past century. This study could bring new insights into combining antibiotics with the simplest of all amino acids. The restoration of sensitivity to the aforementioned antibiotics by a natural compound, already used for clinical purposes, is of extreme importance in an era of proliferation of multiresistant bacteria. The in vivo use of this amino acid in evaluating its effectiveness against infections should be investigated. The low cost of this molecule can also make it easy to use even in low-income countries.

Synergistic Combination of Aztreonam and Ceftazidime–Avibactam—A Promising Defense Strategy against OXA-48 + NDM Klebsiella pneumoniae in Romania

With the increasing burden of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), including high rates of healthcare-associated infections, treatment failure, and mortality, a good therapeutic strategy for attacking this multi-resistant pathogen is one of the main goals in current medical practice and necessitates the use of novel antibiotics or new drug combinations. Objectives: We reviewed the clinical and microbiological outcomes of seven patients treated at the “Agrippa Ionescu” Clinical Emergency Hospital between October 2023 and January 2024, aiming to demonstrate the synergistic activity of the ceftazidime–avibactam (C/A) plus aztreonam (ATM) combination against the co-producers of blaNDM + blaOXA-48-like CR-Kp. Material and Methods: Seven CR-Kp with blaNDM and blaOXA-48 as resistance mechanisms were tested. Seven patients treated with C/A + ATM were included. The synergistic activity of C/A + ATM was proven through double-disk diffusion in all seven isolates. Resistance mechanisms like KPC, VIM, OXA-48, NDM, IMP, and CTX-M were assessed through immunochromatography. Results: With a mean of nine days of treatment with the synergistic combination C/A + ATM, all patients achieved clinical recovery, and five achieved microbiological recovery. Conclusions: With the emerging co-occurrence of blaOXA-48 and blaNDM among Kp in Romania, the combination of C/A and ATM could be a promising therapeutic option.

Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii

Within the global rise of antimicrobial resistance enhanced by the COVID-19 pandemic, where Acinetobacter baumannii has been distinguished as an emerging multi-resistant pathogen, essential oils, become the focus of novel therapeutic approaches. Hypothesizing that encapsulated Origanum heracleoticum L. and Thymus vulgaris L. essential oils could express multi-target approach against A. baumannii, this study aimed to develop microencapsulated systems with optimal technological qualities using 2-hydroxypropyl-β-cyclodextrin as a carrier, and to evaluate their pharmacological potential against A. baumannii, and their morphological and physicochemical characteristics, safety and stability profiles. The highest yield and encapsulation efficiency were obtained with 1:10 essential oil to carrier, and 1.5:10 carrier to water w/w ratios. The formation of inclusion complexes was confirmed by Fourier Transform Infrared Spectroscopy. Both microencapsulates achieved improved homogeneity, particle surface, and thermal stability compared with the pure carrier. Dominant bioactive compounds (carvacrol and p-cymene in O. heracleoticum essential oil, and thymol and p-cymene in T. vulgaris essential oil) remained the most abundant after encapsulation. While non-encapsulated essential oils revealed similar antimicrobial activity towards clinical A. baumannii isolates obtained from COVID-19 patients, encapsulated O. heracleoticum essential oil inhibited the bacterial growth at lower concentrations than T. vulgaris essential oil microencapsulate. All samples significantly reduced the formation of A. baumannii biofilm, for at least 53.90% towards the most infective isolate according to the Caenorhabditis elegans assay. Further, in silico molecular docking study revealed strong interaction pattern of carvacrol and thymol with the outer membrane protein A, which is the main factor for the A. baumannii biofilm formation. Cytotoxicity investigation on human lung A549 cells showed high survival rate in the presence of all tested concentrations, and the stability study revealed notable preservation of the bioactives’ content and pharmacological potential. Altogether, microencapsulated essential oils exhibited a multi-target approach towards A. baumannii, with satisfactory preserving capability during storage.

USE OF LIFE–VEST AND COMPLEX RE–IMPLANTATION OF CRT–D IN PATIENT WITH POCKET INFECTION BY MULTIRESISTENT S. AUREUS AND PERSISTENCE OF LEFT SUPERIOR VENA CAVA

Abstract Patient with primary hypokinetic dilated cardiomyopathy, previously underwent coronary angioplasty with stent implantation on MO branch and subsequent implantation of CRT–D in right subclavian region for persistence of left superior vena cava and complicated left sided implantation; hypertensive, dyslipidaemic, diabetic. Repeated subsequent surgery for shock channel malfunction with re–implantation of right ventricular lead. He came to our observation for infection of the CRT–D pocket by multiresistant Staphylococcus Aureus treated by intravenous antibiotic therapy and explantation of the infected device. We therefore proceeded to discharge the patient with Life–Vest as a bridging strategy until re–implantation and continued with long–acting antibiotic therapy administered every fortnight. After about 8 weeks, once the presence of infectious/inflammatory processes has been ruled out, CRT–D reimplantation is performed, after prophylaxis with Vancomycin, in the right subclavian region under sterile conditions and in the absence of complications. The management of cardiac device infections represents a challenge for the cardiologist especially in the complex patient with a history of re–interventions in which multi–resistant pathogens are often found. This clinical case demonstrates how collegial patient assessment and long–term protection strategies, such as the use of a Life–Vest, can achieve the diagnostic–therapeutic goal.

Insertion sequence IS6770 modulates potassium symporter kup transcription in Enterococcus faecalis JH2-2 under low pH conditions

Enterococcus faecalis is a phylogenetically and industrially relevant microorganism associated with Lactic Acid Bacteria. Some strains of this bacterium are employed as probiotics in commercial applications, while others serve as the principal component in starter cultures for artisanal regional cheese production. However, over the last decade, this species has emerged as an opportunistic multiresistant pathogen, raising concerns about its impact on human health. Recently, we identified multiple potassium transporter systems in E. faecalis, including the Ktr systems (KtrAB and KtrAD), Kup, KimA and Kdp complex (KdpFABC). Nevertheless, the physiological significance of these proteins remains not fully understood. In this study, we observed that the kup gene promoter region in the JH2–2 strain was modified due to the insertion of a complete copy of the IS6770 insertion sequence. Consequently, we investigated the influence of IS6770 on the expression of the kup gene. To achieve this, we conducted a mapping of the promoter region of this gene in the E. faecalis JH2–2 strain, employing fluorescence gene reporters. In addition, a transcriptional analysis of the kup gene was executed in a strain derived from E. faecalis V583 that lacks the IS30-related insertion element, facilitating the identification of the transcriptional start site. Next, the expression of the kup gene was evaluated via RT-qPCR under different pH stressful conditions. A strong upregulation of the kup gene was observed at an initial pH of 5.0 in the strain derived from E. faecalis V583. However, the activation of transcription was not observed in the E. faecalis JH2–2 strain due to the hindrance caused by the presence of IS6770. Besides that, our computational analysis of E. faecalis genomes elucidates a plausible association between transposition and the regulation of the kup gene. Remarkably, the ubiquitous presence of IS6770 throughout the phylogenetic tree implies its ancient existence within E. faecalis. Moreover, the recurrent co-occurrence of IS6770 with the kup gene, observed in 30 % of IS6770-positive strains, alludes to the potential involvement of this genomic arrangement in the adaptive strategies of E. faecalis across diverse niches.

A Robust Strategy Against Multi-Resistant Pathogens in Oral Health: Harnessing the Potency of Antimicrobial Peptides in Nanofiber-Mediated Therapies

A Robust Strategy Against Multi-Resistant Pathogens in Oral Health: Harnessing the Potency of Antimicrobial Peptides in Nanofiber-Mediated Therapies

Preliminary Study of Antibiotics Susceptibility Testing and Pathogens Associated with Nosocomial Infections in a Tertiary Hospital

Background: Health care associated with multiresistant pathogens is rising globally. As nosocomial infections (NIs) could increase hospital stay, morbidity, mortality and disability, therefore the aim of this preliminary study was to define antibiotics and pathogens associated with NIs in a main tertiary hospital in Isfahan, Iran. Methods: The data were extracted from the official database of hospital NIs records. For each patient, the reported infections were abbreviated as: UTI-SUTI, VAE-PVAP, BSI-LCBI, SSI-DIP and so on. For continuous variables, mean ± standard deviation, and for categorical varia-bles, frequency was used. Results: The study population was 5542 patients, comprised of males (n=3282) and females (n=2260). With a minimum of 15 and a maximum of 99, the mean age in 5313 patients was 58.5 ± 19.1 years old. The highest reported NIs (n= 77%) were associated with the ages between 30-80 years old. Sites of NIs in 93% were as: VAE-PVAP- VAE-IVAC; 31%, UTI-SUTI; 30%, SSI-DIP; 19%, BSI-LCBI; 13%, and other individual infection (7%) with the main pathogens associated with Acinetobacter baumannii, Klebsiella pneumonia, Candida and Staphylococcus spp. Antibiotic susceptibilty testing showed the most sensitivity of isolates against Vancomycin (62%), Gentamicin (59%), Ampicillin (44%), Amikacin (35%) and Co-trimoxazol (32%). Conclusion: As most NIs are avoidable, for commissioning an efficient surveillance system, further study of pathogens in relation to evidence-based antibiotic-therapy and advanced infection control program is suggested to be valuable.

Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach

IntroductionAntibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. ObjectiveThis study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. Methods: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. ResultsThe results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of −9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of −8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. ConclusionIn conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.

Antibacterial and antibiotic-modifying activity of the commercialized essential oil of Copaifera spp. Associated with LED lights against a Staphylococcus aureus strain

Copaiba oil is widely used in medicine due to its antibacterial, anti-inflammatory, healing, antiviral, antiseptic and analgesic properties. Thus, the main objective of the study is to evaluate the antibacterial activity and modifier of the antibiotic action of the commercialized essential oil of four species of Copaifera spp. in combination with Ampicillin and LED lights against the multidrug-resistant strain of S. aureus (SA 10). The essential oil was obtained commercially through the dōTERRA® company. The evaluation of the antibacterial and modulating activity was performed using the microdilution methodology in a 96-well plate, using blue 415 nm, red 620 nm and yellow 590 nm LEDs and Ampicillin at an initial concentration of 1.024 µg/mL. The experiments were carried out in triplicate and submitted to ANOVA statistical analysis, considering a significant value of p < 0,05. The essential oil of Copaifera spp. did not show antibacterial activity alone, but showed significant modifying activity when combined with Ampicillin in the absence of LED and with red LED. However, the yellow LED and the blue LED had no significant modulating effect. The results suggest the presence of an enzymatic mechanism of resistance, indicating relevance for the development of future scientific research, aiming to help in the treatment of lesions caused by multiresistant pathogens.

Bioinspired phenol-based coatings for medical fabrics against antimicrobial resistance

Multi-resistant pathogens can cause several nosocomial infections that can harm hospital interventions or undermine biological processes. In this scenario, the development of novel and efficient antimicrobial materials is essential for reducing pathogen spread. Though many approaches have been followed with this aim, scalability, safety, and efficiency concerns still hamper their clinical transfer. In this work, we overcome these limitations by co-polymerizing phenolic derivatives with amino-terminal ligands. The resulting coatings are successfully applied to woven and non-woven-based materials used in healthcare: paper, cotton and polypropylene. Moreover, the coatings demonstrate multi-pathway antimicrobial activity against six bacteria (E. coli, P. aeruginosa, S. aureus, methicillin-resistant S. aureus, E. faecalis, and B. subtilis) and two fungi (C. albicans and C. auris), a fact attributed to i) reactive oxygen species generation over time and ii) protic amino groups exposed on the surface. After 180 min, viable bacteria are reduced by more than 99.9 %, with a comparable decline in fungi after 24 h. As a proof-of-concept, coated commercial band-aids tested on skin ex vivo reduced bacterial growth by about 90 %. Considering these results and long-lasting, in vitro biocompatibility, scalability and eco-friendly technology, these coatings represent a promising alternative to be applied in healthcare environments, avoiding pathogen spread, infections and antimicrobial resistance.

Elimination and penetration of amikacin into urine in patients with decreased glomerular filtration rate.

Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Patients with estimated GFR (eGFR) <30mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30mL/min (89.75 vs 186.0mg/L, P<.0001; 200.5 vs 830.0mg/L, P<.0001; and 126.0 vs 408.0mg/L, P<.0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13h after dose administration was dependent on eGFR (r2=0.6144, P<.0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.

Gram negative bacteria related urinary tract infections: spectrum of antimicrobial resistance over 9 years in a University tertiary referral Hospital.

Overuse of antibiotics has led to an increase in antimicrobial resistance (AMR) worldwide, with a negative impact on the healthcare system and the patients. In this context, our study aims to assess the current AMR patterns of urinary tract infections (UTIs) associated to Gram-negative bacteria. Thus, we provide useful information for doctors dealing with prophylactic and therapeutic empiric therapies. We retrospectively analysed more than 650,000 urine cultures collected in the Microbiology Department of a referral University Hospital of Southern England from January 2014 to December 2022. AMR spectra for 164,059 Gram-negative associated (UTIs) were analysed. The lowest percentage of resistance was found for Amikacin (2.30%), Gentamicin (5.89%) and Co-Amoxiclav (10.49%). Over a 9-year time, there was no significant change in resistance to Amikacin (2.04% in 2014 compared to 2.18% in 2022; p = 0.602) and to Fosfomycin (11.50% in 2014 versus 16.65% in 2022; p = 0.577). Overall, the trend of AMR significantly rose for Cefalexin (17.96-18.42%; p < 0.0001), Co-amoxiclav (9.46-12.69%; p < 0.0001), Nitrofurantoin (10.20-14.18%; p < 0.0001) and Piperacillin/Tazobactam (14.52-18.96%; p < 0.0001). Gram-negative resistance spectrum towards Ciprofloxacin (11.83-9.01%; p < 0.0001), Gentamicin (6.29-5.26%; p < 0.0001), Pivmecillinam (26.88-11.02%; p < 0.0001), Trimethoprim (36.72-29.23%; p < 0.0001) and Ampicillin/Amoxicillin (65.20-57.99%; p < 0.0001) significantly decreased. Despite the application of national and international guidelines for prophylaxis and treatment of UTIs, the spectrum of resistance for the most common antibiotics is still changing. Clinicians in primary and secondary care must keep that in mind when prescribing antibiotics for suspected UTI and sepsis associated with Gram-negative infections Up-to-date therapeutic strategies can help implement treatment of UTI, reducing selection of multi-resistant pathogens and providing more accurate care for patients. Future studies will be required to help clinicians and keep the guidelines updated.

Profiling Antibiotic Susceptibility among Distinct Enterococcus faecalis Isolates from Dental Root Canals.

Enterococcus faecalis, a leading multi-resistant nosocomial pathogen, is also the most frequently retrieved species from persistently infected dental root canals, suggesting that the oral cavity is a possible reservoir for resistant strains. However, antimicrobial susceptibility testing (AST) for oral enterococci remains scarce. Here, we examined the AST profiles of 37 E. faecalis strains, including thirty-four endodontic isolates, two vanA-type vancomycin-resistant isolates, and the reference strain ATCC-29212. Using Etest gradient strips and established EUCAST standards, we determined minimum inhibitory concentrations (MICs) for amoxicillin, vancomycin, clindamycin, tigecycline, linezolid, and daptomycin. Results revealed that most endodontic isolates were susceptible to amoxicillin and vancomycin, with varying levels of intrinsic resistance to clindamycin. Isolates exceeding the clindamycin MIC of the ATCC-29212 strain were further tested against last-resort antibiotics, with 7/27 exhibiting MICs matching the susceptibility breakpoint for tigecycline, and 1/27 reaching that of linezolid. Both vanA isolates confirmed vancomycin resistance and demonstrated resistance to tigecycline. In conclusion, while most endodontic isolates remained susceptible to first-line antibiotics, several displayed marked intrinsic clindamycin resistance, and MICs matched tigecycline's breakpoint. The discovery of tigecycline resistance in vanA isolates highlights the propensity of clinical clone clusters to acquire multidrug resistance. Our results emphasize the importance of implementing AST strategies in dental practices for continued resistance surveillance.