Skin Colonization Research Articles

Exploring Candida auris in its habitat

Candida auris colonizes human skin and causes life-threatening fungal bloodstream infections. In this issue of Cell Host & Microbe, Huang etal. introduce a murine model of C.auris skin colonization to explore the role of distinct clades, immune signaling pathways, antibiotics, and disinfectants on fungal persistence in or clearance from its habitat.

Methicillin-resistant Staphylococcus aureus from infected skin lesions present several virulence genes and are associated with the CC30 in Brazilian children with atopic dermatitis

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory skin disease and colonization by Staphylococcus aureus may affect up to 100% of these patients. Virulent and resistant isolates can worsen AD patient clinical condition and jeopardize the treatment. We aimed to detect virulence genes and to evaluate the biofilm production of S. aureus isolates from infected skin lesions of children with AD. Methicillin resistance was detected by phenotypic and molecular tests and the virulence genes were detected by PCR. Biofilm formation was assessed by bacterial growing on microtiter plates and later stained with safranin. Genotyping was performed by Pulsed-Field Gel Electrophoresis and Multilocus Sequence Typing. Among 106 AD patients, 55 (51.8%) had developed S. aureus cutaneous infections and 23 (41.6%) were methicillin-resistant (MRSA). All 55 isolates carried the fnbA, hla, icaA, sasG, and seu genes, and more than 70% presented cna, eap, ebpS, hlg, and pvl genes. Clonal complex (CC) 30 was the main lineage found (34.5%), especially among MRSA isolates (52.2%). The egc cluster and the bbp gene were significantly the most frequent in MRSA isolates and in USA1100/ST30/CC30 lineage. Most of the isolates (74.5%) were non-biofilm producers and many of them only started to produce it in the presence of fibrinogen. There was no significant association between S. aureus isolates features and the AD severity. This study demonstrated a high frequency of CC30 MRSA isolates presenting several virulence genes in infected skin lesions of AD children in Brazil, that may influence the severity of the disease and the treatments required.

A Slimy Business: the Future of Fish Skin Microbiome Studies.

Fish skin contains a mucosal microbiome for the largest and oldest group of vertebrates, a location ideal for microbial community ecology and practical applications in agriculture and veterinary medicine. These selective microbiomes are dominated by Proteobacteria, with compositions different from the surrounding water. Core taxa are a small percentage of those present and are currently functionally uncharacterized. Methods for skin sampling, DNA extraction and amplification, and sequence data processing are highly varied across the field, and reanalysis of recent studies using a consistent pipeline revealed that some conclusions did change in statistical significance. Further, the 16S gene sequencing approaches lack quantitation of microbes and copy number adjustment. Thus, consistency in the field is a serious limitation in comparing across studies. The most significant area for future study, requiring metagenomic and metabolomics data, is the biochemical pathways and functions within the microbiome community, the interactions between members, and the resulting effects on fish host health being linked to specific nutrients and microbial species. Genes linked to skin colonization, such as those for attachment or mucin degradation, need to be uncovered and explored. Skin immunity factors need to be directly linked to microbiome composition and individual taxa. The basic foundation has been laid, and many exciting future discoveries remain.

Skin and Nasal Colonization with Methicillin Resistant Staphylococcus Aureus in Children with Atopic Dermatitis

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial etiologies, Staphylococcus aureus (S.aureus) and methicillinresistant S.aureus (MRSA) that naturally colonize skin and nose are prevalent among children with AD. Objectives: was to determine the prevalence of S.aureus and MRSA colonization of skin lesions and nose of AD children. Methodology: 40 children diagnosed as AD from Dermatology Clinic of Najran Armed Forces Hospital, Saudi Arabia, were included in the study; separate swabs from skin lesions & nose of each AD patient were tested for S.aureus and MRSA colonization using the conventional culture based Vitek 2 system and the molecular BD Max MRSA XT assay. Results: Using the conventional Vitek 2 system, the prevalence of skin and nasal colonization with S.aureus in AD patients were 25% and 30% respectively while skin and nasal colonization with MRSA were 7.5% and 7.5% respectively, the BD Max MRSA XT assay identified correctly S.aureus with overall 96 % sensitivity, 100 % specificity and 98 % diagnostic accuracy and identified 100 % of MRSA strains. Conclusion: The increase in prevalence of skin and nasal colonization with S.aureus and MRSA among AD children raises the concern about importance of the accurate and rapid molecular diagnostic techniques for preventing the potential risk of MRSA transmission

Alcohol (70%) versus alcoholic chlorhexidine solution (0.5%) in skin antisepsis for neuraxial blocks: a randomized clinical trial.

to compare the use of 0.5% alcoholic chlorhexidine and 70% alcohol in skin antisepsis for neuraxial blocks. this is a non-inferiority randomized clinical trial, with two parallel arms. Seventy patients who were candidates for neuraxial block were randomly allocated to group A (n = 35), in whom antisepsis was performed with 0.5% alcoholic chlorhexidine, or to group B (n = 35), in whom we used 70% hydrated ethyl alcohol. Swabs were harvested for culture at three times: before antisepsis, two minutes after application of the antiseptic, and immediately after puncture. The samples were sown in three culture media and the number of colony forming units (CFU) per cm² was counted. there was no difference between the groups regarding age, sex, body mass index, time to perform the block or type of block. There were no differences between groups in the CFU/cm² counts before antisepsis. There was less bacterial growth in group B two minutes after application of the antiseptic (p = 0.048), but there was no difference between the groups regarding the number of CFU/cm² at the end of the puncture. 70% alcohol was more effective in reducing the number of CFU/cm² after two minutes, and there was no difference between the two groups regarding skin colonization at the end of the procedure. These results suggest that 70% alcohol may be an option for skin antisepsis before neuraxial blocks. Trial registration: ClinicalTrials.gov, NCT02833376.

Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies

Candida auris is an emerging multi-drug-resistant human fungal pathogen. C.auris skin colonization results in environmental shedding, which underlies hospital transmissions, and predisposes patients to subsequent infections. We developed a murine skin topical exposure model for C.auris to dissect risk factors for colonization and to test interventions that might protect patients. We demonstrate that C.auris establishes long-term residence within the skin tissue compartment, which would elude clinical surveillance. The four clades of C.auris, with geographically distinct origins, differ in their abilities to colonize murine skin, mirroring epidemiologic findings. The IL-17 receptor signaling and specific arms of immunity protect mice from long-term C.auris skin colonization. We further determine that commonly used chlorhexidine antiseptic serves as a protective and decolonizing agent against C.auris. This translational model facilitates an integrated approach to develop strategies to combat the unfolding global outbreaks of C.auris and other skin-associated microbial pathogens.

Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls

Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls

Staphylococcus epidermidis-Skin friend or foe?

Author summaryOur skin is our first line of defense against environmental and pathogenic challenges. It is densely populated by a flora of bacteria, fungi, and viruses that normally interact with each other and with our immune system to promote skin health and homeostasis. Staphylococcus epidermidis is one of the most abundant bacterial colonizers of healthy human skin. While the field has historically assumed that all S. epidermidis isolates behave similarly, emerging evidence suggests that colonization by specific strains of S. epidermidis can either help or hurt the skin barrier depending on the context. In this short review, we discuss what is currently understood about S. epidermidis strain-level diversity and evaluate costs and benefits of S. epidermidis skin colonization. We challenge the current dogma that “all S. epidermidis strains behave equally” and posit that behavior is in fact highly context and strain dependent. Finally, in light of current proposals to use skin commensals as nonantibiotic treatments for acute or chronic skin diseases, we conclude that more work is urgently needed to fully understand the pathogenic and protective roles of commensals before we use them therapeutically.

Microbiological efficacy and skin tolerance of commonly used nonantiseptic inpatient bathing practices in non-ICU settings: A systematic review

BackgroundNonantiseptic bathing practices among inpatients and residents of nursing homes vary in terms of frequency, bathing type and product. We performed a systematic review to compare the efficacy of different bathing practices in reducing skin colonization, health care-associated infections (HAI) or their impact on skin integrity. MethodsWe searched Medline and Embase up until February 2018 testing a combination of terms for 3 concepts: (1) personal hygiene, (2) inpatients, (3) skin colonization, integrity or HAIs. Studies set in ICUs or including children were excluded. This review was registered in PROSPERO: CRD42018091639. ResultsSeven studies were included. No statistically significant impact in terms of reduced skin colonization was described irrespective of bathing product, type or frequency except for a reduced burden of C difficile on the skin of infected patients after showering compared to bathing. One study addressing impact on HAI did not detect a significant difference when a waterless no-rinse product was used. Integrity of the skin was better preserved by no-rinse products. ConclusionsNo study described a statistically significant reduction of bacterial skin colonization or incidence of HAI after bathing hospitalized patients with nonantiseptic products. However, waterless no-rinse products were associated with less skin damage in most studies.

Investigation of Pansusceptible Pseudomonas aeruginosa Meningitis Cases in Patients With External Ventricular Devices

Background: During a 2-month period at an academic medical system, 4 cases of pansusceptible P. aeruginosa (PsA) meningitis were identified among neuroscience intensive care unit (NSICU) patients with an external ventricular device (EVD). Methods: We reviewed microbiology data for the previous 2 years to determine background PsA rates and to identify additional cases of PsA meningitis. A case was defined as the isolation of PsA from a CSF specimen. We convened a multidisciplinary group of stakeholders to review medical records of case patients and to conduct a series of observational rounds. Scalp swab specimens were collected from NSICU patients to detect possible skin colonization. Pulsed-field gel electrophoresis (PFGE) analyses were performed on PsA isolates from the 4 case patients and 5 patients with PsA isolates from other body sites. Results: There was no hospital-wide increase in PsA incidence, and no patient without an EVD had PsA cultured from CSF. Infections occurred, on average, 10 days (range, 6–15 days) after EVD insertion. Cases were geographically dispersed in the NSICU and did not share common staff. None of the PsA isolates were genetically related and all scalp cultures were negative. Observations included multiple opportunities for contact with water sources: sinks in proximity to the head of the bed, storage of supplies next to sinks, reuse of bath basins, and use of dilute peroxide to clean surgical wounds. Multiuse shampoos, conditioners and lotions, not approved for hospital use, were found on the unit. Furthermore, 3 of 4 patients received cefazolin >24 hours after 6 of their 7 neurosurgeries for an average of 4.7 days (range, 0.8–4 days). Care practices were changed to mitigate contact between EVD sites and environmental water sources, and extended cefazolin surgical prophylaxis was discontinued. EVD practices were revised, and clinical teams had their competency confirmed. No additional cases have been identified in the 16 months following these interventions. Conclusions: This cluster of EVD infections was likely caused by patient care practices that resulted in independent introductions of PsA from multiple nonsterile or contaminated water sources. Antibiotic selection of PsA by extended use of cefazolin perioperative prophylaxis may have also contributed. EVD care practices should be designed to limit contact between and EVD insertion sites and nonsterile water sources or potentially contaminated care supplies. To substantiate performance improvement efforts and ensure interinstitutional comparability, a practical, standardized EVD-associated infection surveillance definition is needed.Funding: NoneDisclosures: None

Chlorhexidine MICs Remain Stable Among Antibiotic-Resistant Bacterial Isolates Collected from 2005 to 2019 at Three US Sites

Background: Chlorhexidine bathing reduces bacterial skin colonization and prevents infections in specific patient populations. As chlorhexidine use becomes more widespread, concerns about bacterial tolerance to chlorhexidine have increased; however, testing for chlorhexidine minimum inhibitory concentrations (MICs) is challenging. We adapted a broth microdilution (BMD) method to determine whether chlorhexidine MICs changed over time among 4 important healthcare-associated pathogens. Methods: Antibiotic-resistant bacterial isolates (Staphylococcus aureus from 2005 to 2019 and Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex from 2011 to 2019) were collected through Emerging Infections Program surveillance in 2 sites (Georgia and Tennessee) or through public health reporting in 1 site (Orange County, California). A convenience sample of isolates were collected from facilities with varying amounts of chlorhexidine use. We performed BMD testing using laboratory-developed panels with chlorhexidine digluconate concentrations ranging from 0.125 to 64 μg/mL. After successfully establishing reproducibility with quality control organisms, 3 laboratories performed MIC testing. For each organism, epidemiological cutoff values (ECVs) were established using ECOFFinder. Results: Among 538 isolates tested (129 S. aureus, 158 E. coli, 142 K. pneumoniae, and 109 E. cloacae complex), S. aureus, E. coli, K. pneumoniae, and E. cloacae complex ECVs were 8, 4, 64, and 64 µg/mL, respectively (Table 1). Moreover, 14 isolates had an MIC above the ECV (12 E. coli and 2 E. cloacae complex). The MIC50 of each species is reported over time (Table 2). Conclusions: Using an adapted BMD method, we found that chlorhexidine MICs did not increase over time among a limited sample of S. aureus, E. coli, K. pneumoniae, and E. cloacae complex isolates. Although these results are reassuring, continued surveillance for elevated chlorhexidine MICs in isolates from patients with well-characterized chlorhexidine exposure is needed as chlorhexidine use increases.Funding: NoneDisclosures: None

Room for Improvement: Results of a Baseline Evaluation of Environmental Cleaning in a Resource-Limited Neonatal Unit

Background: Contamination of the near-patient hospital environment including work surfaces and equipment, contributes to skin colonization and subsequent invasive bacterial infections in hospitalized neonates. In resource-limited settings, cleaning of the neonatal ward environment and equipment is seldom standardized and infrequently audited. Methods: A baseline multimodal assessment of surface and equipment cleaning was performed in a 30-bed high-care neonatal ward in Cape Town, South Africa, October 7–9, 2019. Adequacy of routine cleaning was evaluated using ATP bioluminescence assays, fluorescent ultraviolet (UV) markers, and quantitative bacterial surface cultures. For flat surfaces (eg, tables, incubators, trolleys), a 10×10-cm template was used to standardize the swab inoculum; for small equipment and devices with complex surfaces (eg, humidifiers, suction apparatus, stethoscopes), a standard swabbing protocol was developed for each item. Swabs in liquid transport medium were processed in the laboratory by vortexing for 30 seconds, plating onto blood and MacConkey agars, and incubating at 37°C for 48 hours. Manual counting of bacterial colony forming units was performed, followed by conventional biochemical testing and/or VITEK automated identification. Results: Of 100 swabs (58 from surfaces and 42 from equipment), 11 yielded growth of known neonatal pathogens (Enterobacteriaceae, A. baumannii, P. aeruginosa, S. aureus, S. agalactiae, and enterococci), 36 isolated potential neonatal pathogens (mostly coagulase-negative staphylococci). In addition, 4 grew environmental organisms and 49 showed no growth. The highest aerobic colony counts (ACCs) were obtained from swabs of suction tubing, milk kitchen surfaces, humidifiers, and sinks; the median ACC from swabs with any bacterial growth (n = 51) was 3 (IQR, 1–22). Only 40% of the 100 surface and equipment swabs had ATP values <200 relative light units (RLU) threshold for cleanliness. Median ATP values were 301 (IQ range, 179–732) RLUs for surface swabs versus 230 (IQ range, 78–699) RLUs for equipment swabs (P = .233). Of the 100 fluorescent UV markers placed on near-patient surfaces and high-touch equipment, only 23% had been removed after 2 staff shift changes (24 hours later). Surfaces had a higher proportion of UV marker removal than equipment (19 of 58 [32.8%] vs 4 of 42 [9.5%]; P = .008). Conclusions: Environmental cleaning of this neonatal ward was suboptimal, especially for equipment. Improvement of environmental cleaning practices is an important intervention for neonatal infection prevention in resource-limited settings. Future studies should evaluate the impact of staff training, environmental cleaning tools and repeated audit with feedback, on the adequacy of cleaning in neonatal wards.Funding: Funding: for the laboratory work was provided by The Society for Healthcare Epidemiology of America (SHEA) International Ambassador Alumni Research Award and a South African Medical Research Council Self-initiated Research (SIR) Grant to Angela Dramowski, who is supported by a NIH Fogarty Emerging Global Leader Award K43 TW010682.Disclosures: None

Efficacy of Ibrexafungerp (SCY-078) against Candida auris in an In Vivo Guinea Pig Cutaneous Infection Model.

Candida auris has been shown to have a high risk of skin colonization in hospitalized patients, possibly contributing to nosocomial spread. In a guinea pig skin model, animals were evaluated for clinical appearance, tissue fungal burden, histology, and pharmacokinetics. Oral dosing with 10 mg/kg ibrexafungerp (IBX) reduced the severity of lesions and significantly reduced the C. auris fungal burden in infected animals compared with untreated controls. This indicates promise for use of IBX in controlling skin infection and colonization of hospitalized patients.

Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair.

Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium Roseomonas mucosa for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of R. mucosa treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, R. mucosa treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced Staphylococcus aureus burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to R. mucosa treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by R. mucosa persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by R. mucosa, cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of R. mucosa treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.

A Novel Mycovirus Evokes Transcriptional Rewiring in the Fungus Malassezia and Stimulates Beta Interferon Production in Macrophages.

Mycoviruses infect fungi, and while most persist asymptomatically, there are examples of mycoviruses having both beneficial and detrimental effects on their host. Virus-infected Saccharomyces and Ustilago strains exhibit a killer phenotype conferring a growth advantage over uninfected strains and other competing yeast species, whereas hypovirus-infected Cryphonectria parasitica displays defects in growth, sporulation, and virulence. In this study, we identify a double-stranded RNA (dsRNA) mycovirus in five Malassezia species. Sequence analysis reveals it to be a totivirus with two dsRNA segments: a larger 4.5-kb segment with genes encoding components for viral replication and maintenance, and a smaller 1.4-kb segment encoding a novel protein. Furthermore, transcriptome sequencing (RNA-seq) of virus-infected versus virus-cured Malassezia sympodialis revealed an upregulation of dozens of ribosomal components in the cell, suggesting the virus modifies the transcriptional and translational landscapes of the cell. Given that Malassezia is the most abundant fungus on human skin, we assessed the impact of the mycovirus in a murine epicutaneous infection model. Although infection with virus-infected strains was not associated with an increased inflammatory response, we did observe enhanced skin colonization in one of two virus-infected M. sympodialis strains. Noteworthy, beta interferon expression was significantly upregulated in bone marrow-derived macrophages when challenged with virus-infected, compared to virus-cured, M. sympodialis, suggesting that the presence of the virus can induce an immunological response. Although many recent studies have illuminated how widespread mycoviruses are, there are relatively few in-depth studies about their impact on disease caused by the host fungus. We describe here a novel mycovirus in Malassezia and its possible implications in pathogenicity.IMPORTANCEMalassezia species represent the most common fungal inhabitant of the mammalian skin microbiome and are natural skin commensal flora. However, these fungi are also associated with a variety of clinical skin disorders. Recent studies have reported associations of Malassezia with Crohn's disease and pancreatic cancer, further implicating this fungal genus in inflammatory and neoplastic disease states. Because M. sympodialis has lost genes involved in RNA interference (RNAi), we hypothesized Malassezia could harbor dsRNA mycoviruses. Indeed, we identified a novel mycovirus of the totivirus family in several Malassezia species and characterized the MsMV1 mycovirus of M. sympodialis We found conditions that lead to curing of the virus and analyzed isogenic virus-infected/virus-cured strains to determine MsMV1 genetic and pathogenic impacts. MsMV1 induces a strong overexpression of transcription factors and ribosomal genes, while downregulating cellular metabolism. Moreover, MsMV1 induced a significantly higher level of beta interferon expression in cultured macrophages. This study sheds light on the mechanisms of pathogenicity of Malassezia, focusing on a previously unidentified novel mycovirus.

Are three antiseptic paints needed for safe preparation of the surgical field? A prospective cohort study with 239 patients

BackgroundPreoperative skin antisepsis is an essential component of safe surgery. However, it is unclear how many antiseptic paints are needed to eliminate bacteria prior to incision. This study compared microbial skin counts after two and three antiseptic paints.MethodsWe conducted a prospective cohort study in non-emergency patients receiving a cardiac/abdominal surgery with standardized, preoperative skin antisepsis consisting of an alcoholic compound and either povidone iodine (PI) or chlorhexidine (CHX). We obtained three skin swabs from the participant’s thorax/abdomen using a sterile template with a 25 cm2 window: After collection of the first swab prior to skin antisepsis, and once the second and third application of PI/CHX had dried out, we obtained a second and third swab, respectively. Our primary outcome was the reduction in microbial skin counts after two and three paints of PI/CHX.ResultsAmong the 239 enrolled patients, there was no significant difference in the reduction of mean square root-transformed microbial skin counts with three versus two paints (P = 0.2). But distributions of colony forming units (CFUs) decreased from paint 2 to 3 in a predefined analysis (P = 0.002). There was strong evidence of an increased proportion of patients with zero CFU after paint 3 versus paint 2 (P = 0.003). We did not identify risk factors for insufficient reduction of microbial skin counts after two paints, defined as the detection of > 5 CFUs and/or ≥ 1 pathogens.ConclusionsIn non-emergency surgical patients, three antiseptic paints may be superior to two paints in reducing microbial skin colonization prior to surgery.

Staphylococcus saccharolyticus: An Overlooked Human Skin Colonizer.

Coagulase-negative staphylococcal species constitute an important part of the human skin microbiota. In particular, facultative anaerobic species such as Staphylococcus epidermidis and Staphylococcus capitis can be found on the skin of virtually every human being. Here, we applied a culture-independent amplicon sequencing approach to identify staphylococcal species on the skin of healthy human individuals. While S. epidermidis and S. capitis were found as primary residents of back skin, surprisingly, the third most abundant member was Staphylococcus saccharolyticus, a relatively unstudied species. A search of skin metagenomic datasets detected sequences identical to the genome of S. saccharolyticus in diverse skin sites, including the back, forehead, and elbow pit. Although described as a slow-growing anaerobic species, a re-evaluation of its growth behavior showed that S. saccharolyticus can grow under oxic conditions, and, in particular, in a CO2-rich atmosphere. We argue here that S. saccharolyticus was largely overlooked in previous culture-dependent and -independent studies, due to its requirement for fastidious growth conditions and the lack of reference genome sequences, respectively. Future studies are needed to unravel the microbiology and host-interacting properties of S. saccharolyticus and its role as a prevalent skin colonizer.

Ultrasound guidance and risk for intravascular catheter-related infections among peripheral arterial catheters: a post-hoc analysis of two large randomized-controlled trials

BackgroundThe impact on infectious risk of ultrasound guidance at insertion remains controversial in short-term arterial catheters (ACs). The present study investigated the association between ultrasound guidance (US) during AC insertion and major catheter-related infections (MCRI), catheter-related bloodstream infections (CR-BSI) or colonization, using univariate and multivariate marginal Cox model for clustered data. The skin colonization at catheter removal was evaluated to explain our results.ResultsWe used individual data from two multicenter randomized-controlled trials (RCTs) that included a total of 3029 patients, 10 ICUs and 3950 ACs. US guidance was used for 386 (9.8%) catheter placements. In the univariate Cox model analysis, AC insertion with US versus without US exhibited similar risks for MCRI (HR 0.86, CI 95% 0.27–2.72, p = 0.79), CR-BSI (HR 0.87, CI 95% 0.20–3.72, p = 0.85) and catheter colonization (HR 1.31, CI 95% 0.92–1.86, p = 0.13). After adjustment on confounders, risks associated with US guidance remained similar versus non-US for MCRI (HR 0.71, CI 95% 0.23–2.24, p = 0.56), CR-BSI (HR 0.71, CI 95% 0.17–3.00, p = 0.63) and catheter colonization (HR 0.92, CI 95% 0.63–1.34, p = 0.67). No differences between US and non-US for MCRI, CR-BSI and colonization were observed according to the insertion site, radial or femoral. At catheter removal, the skin colonization was similar between US and non-US groups (p = 0.69).ConclusionsUsing the largest dataset ever collected from large multi-centric RCTs conducted with relatively consistent insertion and maintenance catheter protocols, we showed that the risk of infectious complications for ACs inserted under US guidance is not superior compared to those inserted without US guidance.Trial registration These studies were registered within ClinicalTrials.gov (numbers NCT01629550 and NCT 01189682).

Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development.

Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.

Resident macrophages acquire innate immune memory in staphylococcal skin infection.

Staphylococcus aureus (S. aureus) is a common colonizer of healthy skin and mucous membranes. At the same time, S. aureus is the most frequent cause of skin and soft tissue infections. Dermal macrophages (Mφ) are critical for the coordinated defense against invading S. aureus, yet they have a limited life span with replacement by bone marrow derived monocytes. It is currently poorly understood whether localized S. aureus skin infections persistently alter the resident Mφ subset composition and resistance to a subsequent infection. In a strictly dermal infection model we found that mice, which were previously infected with S. aureus, showed faster monocyte recruitment, increased bacterial killing and improved healing upon a secondary infection. However, skin infection decreased Mφ half-life, thereby limiting the duration of memory. In summary, resident dermal Mφ are programmed locally, independently of bone marrow-derived monocytes during staphylococcal skin infection leading to transiently increased resistance against a second infection.