The Influence of Skin Commensals on the Therapeutic Outcomes of Surgically-Debrided Diabetic Foot Infections

In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally presumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenic pathogens, and followed the patients for ≥ 6 months. In 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens

Influence of Skin Commensals on Therapeutic Outcomes of Surgically Debrided Diabetic Foot Infections-A Large Retrospective Comparative Study

In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pathogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs. 24 %, p = 0.23) or microbiological recurrence (11% vs. 17 %, p = 0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, the isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may also be based on oral non-beta-lactam antibiotic agents effective against the corresponding skin pathogens

Pseudomonal Diabetic Foot Infections: Vive la Différence?

Objective To assess the outcomes of diabetic foot infections (DFIs) due to Pseudomonas aeruginosa. Patients and Methods From April 24, 2013 to July 31, 2016, we analyzed data from patients prospectively enrolled in our clinical pathway of DFIs, comparing those with infection due to Pseudomonas with those without infection due to Pseudomonas. Results Overall, we assessed 1018 cases of DFIs: 392 with osteomyelitis and 626 with only soft tissue infections. The prevalence of P aeruginosa in deep wound cultures was 10% (104/1018); of the 1018 cultures, 22 were monomicrobial, 82 were polymicrobial, and 46 were with osteomyelitis. Overall, the patients were treated with a median of 1 surgical debridement and a total of 20 days of antibiotic therapy. In a comparison of crude groups, the proportion of clinical failures was significantly higher with Pseudomonas than with other pathogens (36/104 [35%] vs 218/914 [24%], respectively; P=.02). A multivariate analysis showed that pseudomonal DFIs did not recur more often than nonpseudomonal DFIs (hazard ratio, 1.0; 95% confidence interval, 0.6-1.7). Among the 104 cases of pseudomonal DFIs, there was no association between failure of treatment and the total duration of antibiotic therapy, duration of intravenous therapy, duration of combined antibiotic therapy with more than 1 agent, or duration of oral (fluoroquinolone) therapy. Among 15 cases of pseudomonal recurrence, 2 (13%) developed resistance to the antibiotic agent used for the index episode. Conclusion For DFIs caused by P aeruginosa, other than choosing an antibiotic agent that is active against the organism, it does not appear necessary to treat with a different therapeutic regimen compared with the treatment of nonpseudomonal DFIs. There is no difference

Impact of environmental hygiene interventions on healthcare-associated infections and patient colonization: a systematic review

BACKGROUND Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued in infection prevention and control. Though the literature is evolving rapidly, many institutions still do not consider healthcare environmental hygiene (HEH) very important for patient safety. The evidence for interventions in the healthcare environment on patient colonization and HAI with multidrug-resistant microorganisms (MDROs) or other epidemiologically relevant pathogens was reviewed. METHODS We performed a systematic review according to the PRISMA guidelines using the PubMed and Web of Science databases. All original studies were eligible if published before December 31, 2019, and if the effect of an HEH intervention on HAI or patient colonization was measured. Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, included a complete structural rebuild of the healthcare facility or were implemented during an outbreak. The primary outcome was the comparison of the intervention on patient colonization or HAI compared to baseline or control. Interventions were categorized by mechanical, chemical, human factors, or bundles. Study quality was assessed using a specifically-designed tool that considered study design, sample size, control, confounders, and issues with reporting. The effect of HEH interventions on environmental bioburden was studied as a secondary outcome. FINDINGS After deduplication, 952 records were scrutinized, of which 44 were included for full text assessment. A total of 26 articles were included in the review and analyzed. Most studies demonstrated a reduction of patient colonization or HAI, and all that analyzed bioburden demonstrated a reduction following the HEH intervention. Studies tested mechanical interventions (n = 8), chemical interventions (n = 7), human factors interventions (n = 3), and bundled interventions (n = 8). The majority of studies (21/26, 81%) analyzed either S. aureus, C. difficile, and/or vancomycin-resistant enterococci. Most studies (23/26, 88%) reported a decrease of MDRO-colonization or HAI for at least one of the tested organisms, while 58% reported a significant decrease of MDRO-colonization or HAI for all tested microorganisms. Forty-two percent were of good quality according to the scoring system. The majority (21/26, 81%) of study interventions were recommended for application by the authors. Studies were often not powered adequately to measure statistically significant reductions. INTERPRETATION Improving HEH helps keep patients safe. Most studies demonstrated that interventions in the hospital environment were related with lower HAI and/or patient colonization. Most of the studies were not of high quality; additional adequately-powered, high-quality studies are needed. Systematic registration number: CRD42020204909

Energy fluctuations in a biharmonically driven nonlinear system

We study the fluctuations of work done and dissipated heat of a Brownian particle in a symmetric double well system. The system is driven by two periodic input signals that rock the potential simultaneously. Confinement in one preferred well can be achieved by modulating the relative phase between the drives. We show that in the presence of pumping the stochastic resonance signal is enhanced when analyzed in terms of the average work done on the system per cycle. This is in contrast to the case when pumping is achieved by applying an external static bias, which degrades resonance. We analyze the nature of work and heat fluctuations and show that the steady state fluctuation theorem holds in this system.Comment: 13 pages, 14 figures, revised manuscrip

SmokeHaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health

Background: Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by public and policymakers presents a challenge. We have therefore summarised scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. Methods: We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, grey literature, and experts. Random effect meta-analyses were used to pool the findings. Results: We included 216 papers. Among adult smokers, we confirmed substantially increased risks of lung cancer (Risk Ratio (RR) 10.92, 95% CI 8.28-14.40; 34 studies), COPD (RR 4.01, 95% CI 3.18-5.05; 22 studies) and asthma (RR 1.61, 95% CI 1.07-2.42; 8 studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult non-smokers; and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnoea, and asthma exacerbations in adult and pregnant populations; and active and passive smoking increased the risk of tuberculosis. Conclusions: These findings have been translated into easily digestible content and published on the SmokeHaz website (www.smokehaz.eu)

Brownian motors: noisy transport far from equilibrium

Transport phenomena in spatially periodic systems far from thermal equilibrium are considered. The main emphasize is put on directed transport in so-called Brownian motors (ratchets), i.e. a dissipative dynamics in the presence of thermal noise and some prototypical perturbation that drives the system out of equilibrium without introducing a priori an obvious bias into one or the other direction of motion. Symmetry conditions for the appearance (or not) of directed current, its inversion upon variation of certain parameters, and quantitative theoretical predictions for specific models are reviewed as well as a wide variety of experimental realizations and biological applications, especially the modeling of molecular motors. Extensions include quantum mechanical and collective effects, Hamiltonian ratchets, the influence of spatial disorder, and diffusive transport.Comment: Revised version (Aug. 2001), accepted for publication in Physics Report

Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions

Parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. Once intracellular, Leishmania parasites must evade or deactivate the host's innate and adaptive immune responses in order to survive and replicate. We performed transcriptome profiling using RNA-seq to simultaneously identify global changes in murine macrophage and L. major gene expression as the parasite entered and persisted within murine macrophages during the first 72 h of an infection. Differential gene expression, pathway, and gene ontology analyses enabled us to identify modulations in host and parasite responses during an infection. The most substantial and dynamic gene expression responses by both macrophage and parasite were observed during early infection. Murine genes related to both pro- and anti-inflammatory immune responses and glycolysis were substantially upregulated and genes related to lipid metabolism, biogenesis, and Fc gamma receptor-mediated phagocytosis were downregulated. Upregulated parasite genes included those aimed at mitigating the effects of an oxidative response by the host immune system while downregulated genes were related to translation, cell signaling, fatty acid biosynthesis, and flagellum structure. The gene expression patterns identified in this work yield signatures that characterize multiple developmental stages of L. major parasites and the coordinated response of Leishmania-infected macrophages in the real-time setting of a dual biological system. This comprehensive dataset offers a clearer and more sensitive picture of the interplay between host and parasite during intracellular infection, providing additional insights into how pathogens are able to evade host defenses and modulate the biological functions of the cell in order to survive in the mammalian environment.https://doi.org/10.1186/s12864-015-2237-

X-Ray Versus Magnetic Resonance Imaging in Diabetic Foot Osteomyelitis: A Clinical Comparison

OBJECTIVE Radiographic imaging is an important diagnostic tool in diabetic foot osteomyelitis (DFO). It is unknown whether DFO cases diagnosed with conventional X-ray versus positive Magnetic Resonance Imaging (MRI) differ regarding epidemiology and treatment outcome. Theoretically, signs of inflammation on MRI without bone lesions might be easier to treat and predominate among selected clinical variables. METHODS Our clinical pathway for diabetic foot infections discourages the use of MRI for the diagnosis of DFO. We compared the epidemiology and therapy of non-amputated DFO with positive features on conventional X-ray, MRI, or both. Radiology specialists interpreted the images. The intraoperative aspect of bone during amputation and the results of bone cultures were considered gold standard for DFO diagnosis. RESULTS We prospectively followed 390 DFO episodes in 186 adult patients for a median of 2.9 years and performed 318 conventional X-rays (median costs 100 Swiss Francs; 100 US$) and 47 (47/390; 12$). Among them, 18 episodes were associated with positive MRI findings but lacked bone lesions on X-ray. After debridement, the median duration of systemic antibiotics was 28 days for MRI-only episodes and 30 days for X-ray-positive cases (Wilcoxon-ranksum-test; p=0.26). The corresponding median numbers of surgical debridements were 1 and 1; and remission was achieved in 25% and 27%, respectively. In multivariate logistic regression analysis, MRI-only episodes did not alter remission rate (odds ratio 0.5, 95%CI 0.1-5.2). CONCLUSIONS According to our clinical pathway, DFO episodes with positive MRI findings only did not differ epidemiologically and did not influence the choice of therapy nor remission rate