Device-associated Infections Research Articles

One step antimicrobial coatings for medical device applications based on low fouling polymers containing selenium nanoparticles

All indwelling and implantable medical devices are associated with a risk of infection, and antimicrobial technologies that can provide effective protection against pathogen colonization and biofilm formation over the lifetime of these devices are urgently required. Here, strategies that combine multiple layers of defense have emerged as particularly promising. We have combined a copolymer coating based on 2-hydroxypropyl acrylamide and N-benzophenone acrylamide with novel, optimally sized antimicrobial selenium nanoparticles (Se NPs). The photoreactive polymer allowed the crosslinking and covalent anchoring of the coating in a single step, and the exceptionally low attachment of bacteria was demonstrated. Our results also demonstrated that the incorporation of the antimicrobial Se NPs provides the coating with an additional bactericidal functionality towards the Gram-positive bacteria S. aureus and E. faecalis, which are widely recognized as the most prevalent pathogens linked to medical device-associated infections and more broadly nosocomial infections. The multiple layers of defense provided effective inhibition of the growth of both bacteria strains in areas where the coating had been removed, as well as in the supernatant. Moreover, our results demonstrate the feasibility to modulate the release of Se NPs from the coating by tailoring coating parameters such as the nanoparticle to polymer ratio. Our cytotoxicity study further confirmed the superior biocompatibility of Se NPs compared to the well-established silver nanoparticles over a broad concentration range. Our multifunctional coating approach is expected to be translated into medical device applications due to its ease of manufacture and effective antimicrobial protection.

Fucoidan-Containing, Low-Adhesive Siloxane Coatings for Medical Applications: Inhibition of Bacterial Growth and Biofilm Development.

The deposition of low-adhesive siloxane coatings is a current trend for the non-toxic control of bacterial growth and biofilm formation. Total elimination of biofilm formation has not been reported so far. The aim of this investigation was to study the ability of a non-toxic, natural, biologically active substance, such as fucoidan, to inhibit bacterial growth on similar medical coatings. The fucoidan amount was varied, and its impact on the bioadhesion-influencing surface characteristics, as well as on bacterial cell growth, was investigated. The inclusion of up to 3-4 wt.% brown algae-derived fucoidan in the coatings increases their inhibitory effect, more significantly on the Gram-positive bacterium S. aureus than on the Gram-negative bacterium Escherichia coli. The biological activity of the studied siloxane coatings was ascribed to the formation of a low-adhesive, biologically active surface top layer consisting of siloxane oil and dispersed water-soluble fucoidan particles. This is the first report on the antibacterial activity of fucoidan-containing medical siloxane coatings. The experimental results give reason to expect that relevantly selected, natural biologically active substances can be efficient in the non-toxic control of bacterial growth on medical devices and, as a result, medical device-associated infections.

Device-associated infections in neonatal care units in a middle-income country, 2016–2018

ObjectiveDescribe the device-associated infections in the NICUs in Cali – Colombia, a middle-income country, between August 2016 to December 2018. MethodsObservational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR CI95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. Results226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53–8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33–7.06, p = 0.008). ConclusionsThese results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.

Impact of the COVID-19 pandemic on the incidence, etiology, and antimicrobial resistance of healthcare-associated infections in a critical care unit in Western Qatar.

Healthcare-associated infections (HAIs) in critical patients affect the quality and safety of patient care and increase patient morbidity and mortality. During the COVID-19 pandemic, an increase in the incidence of HAIs, particularly device-associated infections (DAIs), was reported worldwide. In this study, we aimed to estimate the incidence of HAIs in an intensive care unit (ICU) during a 10-year period and compare HAI incidence during the preCOVID-19 and COVID-19 periods. A retrospective, observational study of HAIs in the medical-surgical ICU at The Cuban Hospital was conducted. DAIs included central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and ventilator-associated pneumonia (VAP). Data included the annual incidence of HAIs, etiology, and antimicrobial resistance, using definitions provided by the Centers for Disease Control and Prevention, except for other respiratory tract infections (RTIs). 155 patients with HAI infections were reported, from which 130 (85.5%) were identified during the COVID-19 period. The frequencies of DAIs and non-DAIs were higher during the COVID-19 period, except for Clostridium difficile infections. Species under Enterobacter, Klebsiella, and Pseudomonas dominated in both periods, and higher frequencies of Acinetobacter, Enterococcus, Candida, Escherichia coli, Serratia marcescens, and Stenotrophoma maltophila were noted during COVID-19 period. Device utilization ratio increased to 10.7% for central lines and 12.9% for ventilators, while a reduction of 15% in urinary catheter utilization ratio was observed. DAI incidence was higher during the COVID-19 pandemic, with risks for CLABSI, VAP, and CAUTI increased by 2.79 (95% confidence interval, 0.93-11.21; p<0.0050), 15.31 (2.53-625.48), and 3.25 (0.68-31.08), respectively. The incidence of DAIs increased during the pandemic period, with limited evidence of antimicrobial resistance observed. The infection control program should evaluate strategies to minimize the impact of the pandemic on HAIs.

Ten-year incidence and impact of coronavirus infections on incidence, etiology, and antimicrobial resistance of healthcare-associated infections in a critical care unit in Western Qatar.

Healthcare-associated infections (HAI) in critical patients affect the quality and safety of patient care as they impact morbidity and mortality. During the COVID-19 pandemic, an increase in the incidence rate was reported worldwide. We aim to describe the incidence of HAI in the intensive care unit (ICU) during a 10-year follow-up period and compare the incidence during the pre-COVID-19 and COVID-19 periods. A retrospective observational study of HAI in the medical-surgical ICU at The Cuban Hospital was conducted. The data collected include the annual incidence of HAI, its etiology, and antimicrobial resistance, using the Centers for Disease Control and Prevention definitions, except for other respiratory tract infections (RTIs). A total of 155 patients had HAI, of which 130 (85.5%) were identified during COVID-19. The frequency of device-associated infections (DAI) and non-DAI was higher during COVID-19, except for Clostridium difficile infections. Etiology was frequently related to species of Enterobacter, Klebsiella, and Pseudomonas in both periods, and a higher frequency of Acinetobacter, Enterococcus, Candida, Escherichia coli, Serratia marcescens, and Stenotrophomonas maltophilia was noted during the COVID-19 period. Device utilization ratio increased by 10.7% for central lines and 12.9% for ventilators, while a reduction of 15% in urinary catheter utilization ratio was observed. DAI incidence was higher during the COVID-19, with a 2.79 higher risk of infection (95% CI: 0.93-11.21; p < 0.0050), 15.31 (2.53-625.48), and 3.25 (0.68-31.08) for CLABSI, VAP, and CAUTI, respectively. The incidence of DAI increased during the pandemic period as compared to the pre-pandemic period, and limited evidence of the impact on antimicrobial resistance was observed. The infection control program should evaluate strategies to minimize the impact of pandemics on HAI.

Preclinical performance testing of medical devices with antimicrobial effects

Infections associated with medical device use can have serious consequences for patients. Such healthcare-associated infections are often challenging to treat because of the persistence of microbial biofilms and the presence of antimicrobial-resistant microorganisms. The risks of device-associated infections can be reduced by using medical devices with antimicrobial effects. In this Review, we discuss preclinical performance testing of medical devices with antimicrobial effects, including in vitro strategies, animal models and computational modelling. We examine the clinical performance of antimicrobial bone cements, urinary catheters, venous catheters and wound dressings. Rational preclinical test strategies are needed to obtain information to estimate how well a device will benefit the patient in clinical use. We outline the potential of ex vivo models, microphysiological systems, organoids and medical devices-on-chips as complementary testing strategies. To move preclinical tests from the bench to the bedside, we propose a systems approach to address the many interrelated aspects of medical device interactions using a question-based rubric. The implementation or insertion of medical devices into the body can lead to infections and inflammation, which are often challenging to treat because of the presence of microbial biofilms and antimicrobial-resistant microorganisms. This Review outlines preclinical testing strategies for medical devices with antimicrobial properties to avoid and reduce medical-device-associated infections.

Disinfection of Reusable Laryngoscopes: A Survey about the Clinical Practice in Spain.

Airway device-associated infections resulting from the cross-contamination of reusable laryngoscopes are one of the main causes of healthcare-associated infections. Laryngoscope blades are highly contaminated with various pathogens, including Gram-negative bacilli, which can cause prolonged hospitalization, high morbidity and mortality risks, the development of antibiotic-resistant microorganisms, and significant costs. Despite the Centers for Disease Control and Prevention and the American Society of Anesthesiologists' recommendations, this national survey of 248 Spanish anesthesiologists showed that there is great variability in the processing of reusable laryngoscopes in Spain. Nearly a third of the respondents did not have an institutional disinfection protocol, and 45% of them did not know the disinfection procedure used. Good practices for the prevention and control of cross-contamination can be ensured through compliance with evidence-based guidelines, education of healthcare providers, and audits of clinical practices.

PD35-01 ARTIFICIAL URINARY SPHINCTER DEVICES HARBOR MICROBIAL BIOFILMS THAT RECONSTITUTE DIFFERENTIALLY IN VITRO BY STRAIN AND MEDICAL DEVICE MATERIAL TYPE

You have accessJournal of UrologyCME1 Apr 2023PD35-01 ARTIFICIAL URINARY SPHINCTER DEVICES HARBOR MICROBIAL BIOFILMS THAT RECONSTITUTE DIFFERENTIALLY IN VITRO BY STRAIN AND MEDICAL DEVICE MATERIAL TYPE Glenn Werneburg, Daniel Hettel, Ava Adler, Kenneth Angermeier, Hadley Wood, Sandip Vasavada, Howard Goldman, Raymond Rackley, Bradley Gill, Daniel Shoskes, and Aaron Miller Glenn WerneburgGlenn Werneburg More articles by this author , Daniel HettelDaniel Hettel More articles by this author , Ava AdlerAva Adler More articles by this author , Kenneth AngermeierKenneth Angermeier More articles by this author , Hadley WoodHadley Wood More articles by this author , Sandip VasavadaSandip Vasavada More articles by this author , Howard GoldmanHoward Goldman More articles by this author , Raymond RackleyRaymond Rackley More articles by this author , Bradley GillBradley Gill More articles by this author , Daniel ShoskesDaniel Shoskes More articles by this author , and Aaron MillerAaron Miller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003333.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The artificial urinary sphincter (AUS) is an effective surgical treatment for stress urinary incontinence, and about 9% of AUS devices require removal due to infection. We sought to determine microbial biofilm and metabolite composition on AUS devices, reconstitute biofilms from microbes isolated from indwelling AUSs in an environment mimicking human tissue, and compare their formation across strains and medical material types. We hypothesized AUSs would harbor unique bacterial and metabolite profiles, and that reconstitution of biofilms in vitro may lead to new strategies to prevent device-associated infection. METHODS: Devices from consented patients scheduled for AUS removal or revision were swabbed for biofilm. Samples and controls were subjected to next-generation sequencing, metabolomics, and culture-based approaches. Bacterial isolates were isolated from devices and grown in a continuous-flow stir-tank bioreactor designed to mimic human tissue with an indwelling medical device present, and biofilm-formation on medical device material types was assessed with plate-count assays and scanning electron microscopy. RESULTS: In the 17 analyzed devices, the most commonly detected phyla were Proteobacteria and Firmicutes. Diethanolamine (local anesthetic precursor), threonine-butyl-ester (precursor for peptide synthesis), 5-aminovaleric acid (bacterial metabolite of lysine; GABA agonist) were the most commonly detected metabolites. Microbes isolated from AUS devices consistently reconstituted biofilm in vitro, and biofilm deposition differed by both strain (Staphylococcus lugdunensis the greatest) and material type (polyurethane the greatest and titanium the least, ****p<0.0001). Micrococcus luteus, shown in the Figure 1, had intermediate biofilm overall, with silicone shown in the top micrograph and polyurethane on the bottom. CONCLUSIONS: AUS devices consistently harbored microbiota in the form of biofilms. Isolated strains reconstituted biofilm in vitro across a library of medical device materials. Biofilm formation differed by both strain and material type. Our methods and results open new avenues to screen for inhibitors of biofilm formation and novel medical device materials resistant to infection. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e974 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Glenn Werneburg More articles by this author Daniel Hettel More articles by this author Ava Adler More articles by this author Kenneth Angermeier More articles by this author Hadley Wood More articles by this author Sandip Vasavada More articles by this author Howard Goldman More articles by this author Raymond Rackley More articles by this author Bradley Gill More articles by this author Daniel Shoskes More articles by this author Aaron Miller More articles by this author Expand All Advertisement PDF downloadLoading ...

The First Report of Chryseobacterium gleum Caused Ventriculoperitoneal-shunt Infection in a Child.

To The Editors: Ventriculoperitoneal (VP) shunt is one of the most widely used and effective methods in the treatment of hydrocephalus in childhood. VP shunt infections have been observed in approximately 3.2%–25%, and Chryseobacterium spp. is a rare cause of VP shunt infections.1,2 Herein, we report the first VP shunt infection caused by Chryseobacterium gleum. A 12-month-old female (corrected age 8 months) born via spontaneous vaginal delivery, weighed 700 g at 25 weeks of gestation, was admitted to our emergency department with a fever with a maximum peak temperature of 39°C, projectile vomiting, and decreased oral intake. Her history included long-term ventilation in the neonatal intensive care unit with a diagnosis of moderate bronchopulmonary dysplasia. At 4 months of age, she developed intraventricular hemorrhage and progressive hydrocephalus, and a VP shunt was inserted. She had several episodes of VP shunt infections caused by S. epidermidis and S. aureus. At admission, the patient was febrile, tachycardic (heart rate, 160/min) and tachypneic (respiratory rate of 48/min). Physical examination showed weakness, lethargy and sleepiness. Her total Glasgow Coma Scale score was 12 (E3V4M5). Laboratory tests were as follows: white blood cell (WBC) count: 12.5 × 103/μL (neutrophil 37% and lymphocyte 54%), C-reactive protein: 20 mg/L, procalcitonin: 0.09 μg/L. The cerebrospinal fluid (CSF) WBC count was 120/mm3, protein 107 mg/dL and glucose 42 mg/dL. With the preliminary diagnoses of sepsis and shunt infection, intravenous (IV) cefotaxime (300 mg/kg/day) and IV vancomycin (60 mg/kg/day) was initiated empirically. Peripheral/catheter blood cultures and CSF samples were inoculated into aerobic and anaerobic culture bottles (BacT/ALERT, BioMérieux, Durham, USA). The patient underwent VP shunt externalization. The blood and urine cultures were negative during the patient’s follow-up. Chryseobacterium gleum was isolated in the CSF, shunt and ventricular catheter tip cultures on the 3rd day of treatment. The organism had high-level minimum inhibitory concentration (MIC) levels for meropenem (MIC = 32 μg/mL), imipenem (MIC = 32 μg/mL) and piperacillin-tazobactam (MIC = 250 μg/mL). MIC level of ciprofloxacin was 0.125 μg/mL and trimethoprim-sulfamethoxazole was 0.5 μg/mL. Cefotaxime and vancomycin were switched to IV trimethoprim/sulphamethoxazole (5 mg/kg every 6 hours) and ciprofloxacin (10 mg/kg every 8 hours). On the 5th day of the combined therapy, the patient’s CSF sample was evaluated and showed a WBC count of 30/mm3, glucose 42 mg/dL and protein 360 mg/ dL, and the CSF culture was sterile. Antibiotics were continued for 21 days. The patient was clinically stable, and no adverse effects or seizures were observed during or after the treatment. The extra ventricular drainage was removed, the VP shunt was inserted following 2 consecutive negative CSF cultures, and the patient was discharged. Chryseobacterium species are common in nature but are not found in human flora. Most cases are nosocomial and are frequently associated with immunosuppression or implantable devices. Chryseobacterum gleum is typically a low-virulence organism that can cause serious infections. It has been reported that Chryseobacterum gleum can cause infections such as central-line-associated bloodstream infection, community-acquired pneumonia and urinary tract infection in adults.3–5 Unlike previous reports, Chryseobacterium was isolated in the cerebrospinal fluid in our study. Chryseobacterum gleum commonly colonizes mechanical devices, causing device-associated infections, and can form biofilm. According to this study, VP shunt may be a risk factor for Chryseobacterium gleum infections. This report emphasizes the significance of Chryseobacterium species as a causative agent of a wide range of infections, and VP shunts can pose a risk for this agent. Data on the management of Chryseobacterium is limited. Antimicrobial susceptibility testing guidelines for Chryseobacterium infections should be developed for more effective and accurate treatment.

Genomics of Invasive Cutibacterium acnes Isolates from Deep-Seated Infections.

Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of C. acnes were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that C. acnes subsp. acnes IA1 was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, C. acnes subsp. acnes IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, C. acnes subsp. elongatum (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no P values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of C. acnes, possibly with the exception of C. acnes subsp. elongatum, are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by C. acnes. IMPORTANCE Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) C. acnes isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all C. acnes subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.

Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates.

Bacterial infections are increasingly problematic due to the rise of antimicrobial resistance. Consequently, the rational design of materials naturally resistant to biofilm formation is an important strategy for preventing medical device-associated infections. Machine learning (ML) is a powerful method to find useful patterns in complex data from a wide range of fields. Recent reports showed how ML can reveal strong relationships between bacterial adhesion and the physicochemical properties of polyacrylate libraries. These studies used robust and predictive nonlinear regression methods that had better quantitative prediction power than linear models. However, as nonlinear models' feature importance is a local rather than global property, these models were hard to interpret and provided limited insight into the molecular details of material-bacteria interactions. Here, we show that the use of interpretable mass spectral molecular ions and chemoinformatic descriptors and a linear binary classification model of attachment of three common nosocomial pathogens to a library of polyacrylates can provide improved guidance for the design of more effective pathogen-resistant coatings. Relevant features from each model were analyzed and correlated with easily interpretable chemoinformatic descriptors to derive a small set of rules that give model features tangible meaning that elucidate relationships between the structure and function. The results show that the attachment of Pseudomonas aeruginosa and Staphylococcus aureus can be robustly predicted by chemoinformatic descriptors, suggesting that the obtained models can predict the attachment response to polyacrylates to identify anti-attachment materials to synthesize and test in the future.

Spontaneous Genomic Variation as a Survival Strategy of Nosocomial Staphylococcus haemolyticus.

Staphylococcus haemolyticus is one of the most important nosocomial human pathogens frequently isolated in bloodstream and medical device-related infections. However, its mechanisms of evolution and adaptation are still poorly explored. To characterize the strategies of genetic and phenotypic diversity in S. haemolyticus, we analyzed an invasive strain for genetic and phenotypic stability after serial passage in vitro in the absence and presence of beta-lactam antibiotics. We performed pulsed-field gel electrophoresis (PFGE) of the culture and analyzed five colonies at seven time points during stability assays for beta-lactam susceptibility, hemolysis, mannitol fermentation, and biofilm production. We compared their whole genomes and performed phylogenetic analysis based on core single-nucleotide polymorphisms (SNPs). We observed a high instability in the PFGE profiles at the different time points in the absence of antibiotic. Analysis of WGS data for individual colonies showed the occurrence of six large-scale genomic deletions within the oriC environ, smaller deletions in non-oriC environ regions, and nonsynonymous mutations in clinically relevant genes. The regions of deletion and point mutations included genes encoding amino acid and metal transporters, resistance to environmental stress and beta-lactams, virulence, mannitol fermentation, metabolic processes, and insertion sequence (IS) elements. Parallel variation was detected in clinically significant phenotypic traits such as mannitol fermentation, hemolysis, and biofilm formation. In the presence of oxacillin, PFGE profiles were overall stable over time and mainly corresponded to a single genomic variant. Our results suggest that S. haemolyticus populations are composed of subpopulations of genetic and phenotypic variants. The maintenance of subpopulations in different physiological states may be a strategy to adapt rapidly to stress situations imposed by the host, particularly in the hospital environment. IMPORTANCE The introduction of medical devices and antibiotics into clinical practice have substantially improved patient quality of life and contributed to extended life expectancy. One of its most cumbersome consequences was the emergence of medical device-associated infections caused by multidrug-resistant and opportunistic bacteria such as Staphylococcus haemolyticus. However, the reason for this bacterium's success is still elusive. We found that in the absence of environmental stresses, S. haemolyticus can spontaneously produce subpopulations of genomic and phenotypic variants with deletions/mutations in clinically relevant genes. However, when exposed to selective pressures, such as the presence of antibiotics, a single genomic variant will be recruited and become dominant. We suggest that the maintenance of these cell subpopulations in different physiological states is an extremely effective strategy to adapt to stresses imposed by the host or the infection environment and might contribute for S. haemolyticus survival and persistence in the hospital.

Homology modeling, virtual screening, molecular docking, and dynamics studies for discovering Staphylococcus epidermidis FtsZ inhibitors.

Staphylococcus epidermidis is the most common cause of medical device-associated infections and is an opportunistic biofilm former. Among hospitalized patients, S. epidermidis infections are the most prevalent, and resistant to most antibiotics. In order to overcome this resistance, it is imperative to treat the infection at a cellular level. The present study aims to identify inhibitors of the prokaryotic cell division protein FtsZ a widely conserved component of bacterial cytokinesis. Two substrate binding sites are present on the FtsZ protein; the nucleotide-binding domain and the inter-domain binding sites. Molecular modeling was used to identify potential inhibitors against the binding sites of the FtsZ protein. One hundred thirty-eight chemical entities were virtually screened for the binding sites and revealed ten molecules, each with good binding affinities (docking score range -9.549 to -4.290kcal/mol) compared to the reference control drug, i.e., Dacomitinib (-4.450kcal/mol) and PC190723 (-4.694kcal/mol) at nucleotide and inter-domain binding sites respectively. These top 10 hits were further analyzed for their ADMET properties and molecular dynamics simulations. The Chloro-derivative of GTP, naphthalene-1,3-diyl bis(3,4,5-trihydroxybenzoate), Guanosine triphosphate (GTP), morpholine and methylpiperazine derivative of GTP were identified as the lead molecules for nucleotide binding site whereas for inter-domain binding site, 1-(((amino(iminio)methyl)amino)methyl)-3-(3-(tert-butyl)phenyl)-6,7-dimethoxyisoquinolin-2-ium, and Chlorogenic acidwere identified as lead molecules. Molecular dynamics simulation and post MM/GBSA analysis of the complexes revealed good protein-ligand stability predicting them as potential inhibitors of FtsZ (Figure 1). Thus, identified FtsZ inhibitors are a promising lead compounds for S. epidermidis related infections.

Healthcare-associated infection and antimicrobial consumption in critically ill COVID-19 patients: An observational study

Background: The COVID-19 pandemic has impacted patient and safety issues globally, with special reference to device-associated infection in critical care patients. Objective: To describe the incidence of device-associated infections, non-device-associated respiratory tract infections (RTIs), and antimicrobial use in critical COVID-19 patients during the first six months of the pandemic. Methods: An observational study was conducted in an intensive care unit of a COVID-19-dedicated facility in Western Qatar from April 1 to September 30, 2020. Healthcare-associated infections (HAIs) were confirmed using the CDC definitions as per the corporate infection control program, except for other RTIs. Antimicrobial consumption was registered as days of therapy. Results: During the study period, 30 patients (10.9%) with HAIs were reported from 275 patients admitted. Patients with HAI had a higher median Charlson index, hospital stay, mortality, and APACHE II score on admission. The use of devices (central and peripheral lines, urinary catheters, and ventilators) was more frequent in patients with HAI. The RTI (16 cases) and ventilator-associated pneumonia (VAP) (10 cases) were the most frequent localizations. The infection rate for device-associated infections was 7.84, 3.23, and 2.75 per 1000 device days for VAP, central line-associated bloodstream infection, and catheter-associated urinary tract infection, respectively. 49 isolates related to HAI were identified, with 20 isolates being multidrug-resistant organisms (40.8%). A longer duration of antibiotic therapy was observed in HAI patients (34.1 days versus 9.39 days). Conclusion: The study provides evidence of the impact of COVID-19 on the incidence of device-associated infections in critically ill patients, antibiotics consumption, and antimicrobial resistance.

Characteristics and outcomes of cerebrospinal fluid shunt and drain-associated infections

IntroductionData on infections associated with cerebrospinal fluid shunt (CSF-S) or device-associated infection (CSF-SDI) are limited in adults. We performed a retrospective study to describe characteristics, management, and outcome of CSF-SDI. MethodsAll patients with CSF-SDI and admitted to our institution from January 2013 to December 2019 were included. ResultsAmong 50 patients, fifty-six episodes of CSF-SDI (41 external ventricular device-associated infections (CSF-D) and 15 other shunt infections (CSF-S) were included. The incidence of CSF-SDI was 11.9 %. Fever was the most common symptom (81 %). Enterobacterales were more prevalent in CSF-S than in CSF-D (20 % vs 53 %, p = 0.02). As regards CSF-D, deceased patients (11/41, 27 %) more frequently had a Glasgow coma scale score decreasing from baseline (p < 0.01), lower glycorrhachia (p < 0.01), a higher protein level in CSF (p = 0.001) and a positive control CSF culture (p = 0.031). ConclusionsCSF-SDIs are rare but with a high mortality rate. Mortality was more closely related to the infection than to comorbidities or underlying neurosurgical disease. A second CSF analysis significantly helped to detect patients with CSF-D with a poor prognosis.

Clinically representative rodent model for biomedical device-associated infection

Clinically representative rodent model for biomedical device-associated infection

Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery.

Arthroplasty is a highly successful treatment to restore the function of a joint. The contamination of the implant via bacterial adhesion is the first step toward the development of device-associated infections. The emerging concern about antimicrobial resistance resulted in a growing interest to develop alternative therapeutic strategies. Thus, the increment in the incidence of bacterial periprosthetic infections, the complexity of treating infections caused by organisms growing in biofilms, together with the rise in antibiotic resistant bacteria, expose the need to design novel surfaces that provide innovative solutions to these rising problems. The aim of this work is to develop a coating on titanium (Ti) suitable for inhibiting bacterial adhesion and proliferation, and hence, biofilm formation on the surface. We have successfully prepared polyacrylamide hydrogels containing the conventional antibiotic ampicillin (AMP), silver nanoparticles (AgNPs), and both, AMP and AgNPs. The release of the antibacterial agents from the gelled to aqueous media resulted in an excellent antibacterial action of the loaded hydrogels against sessile S. aureus. Moreover, a synergic effect was achieved with the incorporation of both AMP and AgNPs in the hydrogel, which highlights the importance of combining antimicrobial agents having different targets. The polyacrylamide hydrogel coating on the Ti surface was successfully achieved, as it was demonstrated by FTIR, contact angle, and AFM measurements. The modified Ti surfaces having the polyacrylamide hydrogel film containing AgNPs and AMP retained the highest antibacterial effect against S. aureus as it was found for the unsupported hydrogels. The modified surfaces exhibit an excellent cytocompatibility, since healthy, flattened MC3T3-E1 cells spread on the surfaces were observed. In addition, similar macrophage RAW 264.7 adhesion was found on all the surfaces, which could be related to a low macrophage activation. Our results indicate that AMP and AgNP-loaded polyacrylamide hydrogel films on Ti are a good alternative for designing efficient antibacterial surfaces having an excellent cytocompatibility without inducing an exacerbated immune response. The approach emerges as a superior alternative to the widely used direct adsorption of therapeutic agents on surfaces, since the antimicrobial-loaded hydrogel coatings open the possibility of modulating the concentration of the antimicrobial agents to enhance bacterial killing, and then, reducing the risk of infections in implantable materials.

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe-Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe-metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p &lt; 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

The gene regulatory network of Staphylococcus aureus ST239-SCCmecIII strain Bmb9393 and assessment of genes associated with the biofilm in diverse backgrounds.

Staphylococcus aureus is one of the most prevalent and relevant pathogens responsible for a wide spectrum of hospital-associated or community-acquired infections. In addition, methicillin-resistant Staphylococcus aureus may display multidrug resistance profiles that complicate treatment and increase the mortality rate. The ability to produce biofilm, particularly in device-associated infections, promotes chronic and potentially more severe infections originating from the primary site. Understanding the complex mechanisms involved in planktonic and biofilm growth is critical to identifying regulatory connections and ways to overcome the global health problem of multidrug-resistant bacteria. In this work, we apply literature-based and comparative genomics approaches to reconstruct the gene regulatory network of the high biofilm-producing strain Bmb9393, belonging to one of the highly disseminating successful clones, the Brazilian epidemic clone. To the best of our knowledge, we describe for the first time the topological properties and network motifs for the Staphylococcus aureus pathogen. We performed this analysis using the ST239-SCCmecIII Bmb9393 strain. In addition, we analyzed transcriptomes available in the literature to construct a set of genes differentially expressed in the biofilm, covering different stages of the biofilms and genetic backgrounds of the strains. The Bmb9393 gene regulatory network comprises 1,803 regulatory interactions between 64 transcription factors and the non-redundant set of 1,151 target genes with the inclusion of 19 new regulons compared to the N315 transcriptional regulatory network published in 2011. In the Bmb9393 network, we found 54 feed-forward loop motifs, where the most prevalent were coherent type 2 and incoherent type 2. The non-redundant set of differentially expressed genes in the biofilm consisted of 1,794 genes with functional categories relevant for adaptation to the variable microenvironments established throughout the biofilm formation process. Finally, we mapped the set of genes with altered expression in the biofilm in the Bmb9393 gene regulatory network to depict how different growth modes can alter the regulatory systems. The data revealed 45 transcription factors and 876 shared target genes. Thus, the gene regulatory network model provided represents the most up-to-date model for Staphylococcus aureus, and the set of genes altered in the biofilm provides a global view of their influence on biofilm formation from distinct experimental perspectives and different strain backgrounds.

Synergy between infection control and antimicrobial stewardship programs to control carbapenem-resistant Enterobacterales.

Argentina is the third country in the world with the higher levels of CRE. The primary objective is to achieve an optimal result in the CRE infection rate after the implementation of an IPC program and antimicrobial stewardship programs (ASP) in a large teaching hospital in Argentina. Retrospective, observational study from January 2018 to December 2021, in a 220-bed tertiary care teaching hospital in Buenos Aires province. Actions aimed at CRE control and prevention included CRE and healthcare-associated infection (HAI) surveillance; compliance with hand hygiene, hospital hygiene, contact isolation precautions, and care bundles for the prevention of device-associated infections; optimization of antimicrobial treatments, antimicrobial consumption, education, and feedback. Synergy between an ICP and ASP achieved controlled rate of CRE infections reaching the lowest levels during 2020 (0.08 episodes/1000 patient days). Colonization rate remained stable throughout the study period. Ventilator-associated pneumonia (VAP) rate showed a trend toward lower rates. Compliance with care bundles showed rates >85%. Antimicrobial consumption increased slightly during the study period (15%). Among high-impact antimicrobials, only colistin consumption increased. Our study demonstrates the sustained and beneficial impact of an IPC Program and an ASP to control CRE infection.