Effective elimination of Staphylococcal contamination from hospital surfaces by a bacteriophage-probiotic sanitation strategy: a monocentric study.

Persistent contamination of hospital surfaces and antimicrobial resistance (AMR) are recognized major causes of healthcare-associated infections (HAI). We recently showed that a probiotic-based sanitation (PCHS) can stably decrease surface pathogens and reduce AMR and HAIs. However, PCHS action is slow and non-specific. By contrast, bacteriophages have been proposed as a decontamination method as they can rapidly attack specific targets, but their routine application has never been tested. Here we analyzed the feasibility and effectiveness of phage addition to PCHS sanitation, aiming to obtain a rapid and stable abatement of specific pathogens in the hospital environment. Staphylococcal contamination in the bathrooms of General Medicine wards was analyzed, being such areas the most contaminated and Staphylococci the most prevalent bacteria in such settings. Results showed that a daily phage application by nebulization induced a rapid and significant decrease of Staphylococcus spp. load on treated surfaces, up to 97% more than PCHS alone (p<0.001), suggesting that such system might be considered as a part of prevention and control strategies, to counteract outbreaks of specific pathogens and prevent associated infections

Introduction of NGS in Environmental Surveillance for Healthcare-Associated Infection Control

The hospital environment significantly contributes to the onset of healthcare associated infections (HAIs), representing the most frequent and severe complications related to health care. The monitoring of hospital surfaces is generally addressed by microbial cultural isolation, with some performance limitations. Hence there is need to implement environmental surveillance systems using more effective methods. This study aimed to evaluate next-generation sequencing (NGS) technologies for hospital environment microbiome characterization, in comparison with conventional and molecular methods, in an Italian pediatric hospital. Environmental samples included critical surfaces of randomized rooms, surgical rooms, intensive care units and delivery rooms. The resistome of the contaminating population was also evaluated. NGS, compared to other methods, detected with higher sensitivity the environmental bacteria, and was the only method able to detect even unsearched bacteria. By contrast, however, it did not detect mycetes, nor it could distinguish viable from dead bacteria. Microbiological and PCR methods could identify and quantify mycetes, in addition to bacteria, and PCR could define the population resistome. These data suggest that NGS could be an effective method for hospital environment monitoring, especially if flanked by PCR for species identification and resistome characterization, providing a potential tool for the control of HAI transmission

Impact of a probiotic-based hospital sanitation on antimicrobial resistance and HAI-associated antimicrobial consumption and costs: A multicenter study

Purpose: Antimicrobial resistance (AMR) is one of the major threats to human health, and the high frequency of resistant pathogens in the hospital environment can contribute to the transmission of difficult-to-treat health care-associated infections (HAIs). We recently reported that, compared with conventional chemical cleaning, the use of a microbial-based sanitation strategy (Probiotic Cleaning Hygiene System [PCHS]) was associated with remodulation of hospital microbiota and reduction of HAI incidence. Here, we aimed to analyze the impact of PCHS on AMR and related effects, such as HAI-associated antimicrobial drug consumption and costs. Patients and methods: Five Italian hospitals, enrolled in a multicenter study where conventional sanitation methods were replaced with PCHS, were included in the analysis. The study period included a 6-month observation for each sanitation type. Surface microbiota AMR was analyzed using microarray, nested PCR, antibiogram, and microdilution tests. Drug consumption data and related costs were obtained from the medical records of all hospitalized patients affected by HAIs. Results: PCHS use was associated with up to 99% decrease of the AMR genes harbored by surface hospital microbiota, independently of the resistance types originally present in each individual setting (Pc<0.01). Functional assays confirmed the molecular data, demonstrating a 33%–100% decrease of resistant strains depending on the antibiotic type. Antimicrobial drug consumption associated with HAI onset showed a global 60.3% decrease, with a 75.4% decrease of the associated costs. Conclusion: The spread of AMR in the hospital environment can be limited by the use of sanitation methods to remodulate the hospital microbiota, leading to lower antimicrobial consumption and costs. This approach might be considered as part of broader infection prevention and control strategies

Multivariate analysis of brain metabolism reveals chemotherapy effects on prefrontal cerebellar system when related to dorsal attention network

BACKGROUND: Functional brain changes induced by chemotherapy are still not well characterized. We used a novel approach with a multivariate technique to analyze brain resting state [(18) F]FDG-PET in patients with lymphoma, to explore differences on cerebral metabolic glucose rate between chemotherapy-treated and non-treated patients. METHODS: PET/CT scan was performed on 28 patients, with 14 treated with systemic chemotherapy. We used a support vector machine (SVM) classification, extracting the mean metabolism from the metabolic patterns, or networks, that discriminate the two groups. We calculated the correct classifications of the two groups using the mean metabolic values extracted by the networks. RESULTS: The SVM classification analysis gave clear-cut patterns that discriminate the two groups. The first, hypometabolic network in chemotherapy patients, included mostly prefrontal cortex and cerebellar areas (central executive network, CEN, and salience network, SN); the second, which is equal between groups, included mostly parietal areas and the frontal eye field (dorsal attention network, DAN). The correct classification membership to chemotherapy or not chemotherapy-treated patients, using only one network, was of 50% to 68%; however, when all the networks were used together, it reached 80%. CONCLUSIONS: The evidenced networks were related to attention and executive functions, with CEN and SN more specialized in shifting, inhibition and monitoring, DAN in orienting attention. Only using DAN as a reference point, indicating the global frontal functioning before chemotherapy, we could better classify the subjects. The emerging concept consists in the importance of the investigation of brain intrinsic networks and their relations in chemotherapy cognitive induced changes

Characterization of the Pathogenic Potential of the Beach Sand Microbiome and Assessment of Quicklime as a Remediation Tool

Beach sand may act as a reservoir for potential human pathogens, posing a public health risk. Despite this, the microbiological monitoring of sand microbiome is rarely performed to determine beach quality. In this study, the sand microbial population of a Northern Adriatic Sea beach sand was profiled by microbiological (CFU counts) and molecular methods (WGS, microarray), showing significant presence of potential human pathogens including drug-resistant strains. Consistent with these results, the potential of quicklime as a restoring method was tested in vitro and on-field. Collected data showed that adding 1-3% quicklime (w/w) to sand provided an up to -99% of bacteria, fungi, and viruses, in a dose- and time-dependent manner, till 45 days post-treatment. In conclusion, data suggest that accurate monitoring of sand microbiome may be essential, besides water, to assess beach quality and safety. Moreover, first evidences of quicklime potential for sand decontamination are provided, suggesting its usage as a possible way to restore the microbiological quality of sand in highly contaminated areas

Chemotherapy effects on brain glucose metabolism at rest

Background: A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors. Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses. Methods: We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21). Findings: Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions. Interpretation: The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes

Armida disvelata. L’immagine del velo nella "Gerusalemme liberata"

The essay takes into account the different occurrences of the term ‘veil’ in the Gerusalemme liberata. After an analysis of the metaphorical meanings of the term, the focus moves towards the veils that hide or embellish some of the female characters, in particular Sofronia, Erminia and Armida, bringing to light the different functions – even symbolic – that appear to be connected to this garment.The essay takes into account the different occurrences of the term ‘veil’ in the Gerusalemme liberata. After an analysis of the metaphorical meanings of the term, the focus moves towards the veils that hide or embellish some of the female characters, in particular Sofronia, Erminia and Armida, bringing to light the different functions – even symbolic – that appear to be connected to this garment

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200&nbsp;mg three times daily or placebo for up to 21&nbsp;days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Efficient removal of hospital pathogens from hard surfaces by a combined use of bacteriophages and probiotics: potential as sanitizing agents

Purpose Many hospital-acquired infections (HAI) can be transmitted by pathogens contaminating hospital surfaces, not efficiently controlled by conventional sanitation, which can indeed contribute to the selection of multidrug-resistant (MDR) strains. Bacteriophages have been suggested as decontaminating agents, based on their selective ability to kill specific bacteria. However, there are no data on their stability in detergents and their potential use in routine sanitation. On the other hand, a probiotic-based sanitation (Probiotic Cleaning Hygiene System, PCHS) was recently shown to stably reduce pathogens on treated surfaces. However, its action is not specific and slow, being based on competitive antagonism. This work was aimed to assess the effectiveness of a combined use of phages and PCHS in removing HAI-associated pathogens from different hard surfaces. Methods The decontamination ability of phages in PCHS was tested in vitro and in situ, against drug-susceptible or resistant S. aureus, E. coli and P. aeruginosa strains, and using bacterial densities similar to those detected on hospital surfaces. Results Phages targeted efficiently all tested bacteria, maintaining their full activity when added to PCHS detergent. Notably, the combined use of phages and PCHS not only resulted in a rapid reduction (up to >90%) of the targeted pathogens, but, due to the stabilizing effect of probiotics, the pathogens were maintained at low levels (>99%) also at later times, when instead the effect of phages tends to diminish. Conclusion These results suggest that a combined biological system might be successfully used in hospital sanitation protocols, potentially leading to an effective and safe elimination of MDR pathogens from the hospital environment