Clustering and multiple-spreading events of nosocomial severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: There is growing evidence that super-spreading events (SSEs) and multiple-spreading events (MSEs) are a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data regarding the possibility of SSEs or MSEs in healthcare settings are limited. METHODS: This study was performed at a tertiary-care hospital in Korea. We analysed the nosocomial COVID-19 cases that occurred in healthcare workers and inpatients and their caregivers between January and 20th December 2020. Cases with two to four secondary cases were defined as MSEs and those with five or more secondary cases as SSEs. FINDINGS: We identified 21 nosocomial events (single-case events, N = 12 (57%); MSE + SSE, N = 9 (43%)) involving 65 individuals with COVID-19. Of these 65 individuals, 21 (32%) were infectors. The infectors tended to have a longer duration between symptom onset and diagnostic confirmation than did the non-infectors (median two days vs zero days, P=0.08). Importantly, 12 (18%) individuals were responsible for MSEs and one (2%) for an SSE, which collectively generated 35 (54%) secondary cases. CONCLUSION: In a hospital with thorough infection-control measures, approximately 70% of the nosocomial cases of COVID-19 did not generate secondary cases, and one-fifth of the infectors were responsible for SSEs and MSEs, which accounted for approximately half of the total cases. Early case identification, isolation, and extensive contact tracing are important for the prevention of transmission and SSEs.

Outbreak of carbapenemase-producing Enterobacteriaceae associated with a contaminated water dispenser and sink drains in the cardiology units of a Korean hospital.

BACKGROUND: Concerns are growing over the importance of the hospital water environment for the transmission of carbapenemase-producing Enterobacteriaceae (CPE). AIM: To report a large outbreak in the cardiology units involving intensive care units (ICUs) and wards at a tertiary-care hospital. METHODS: This was a contact tracing, case-control study to find the risk factors for acquisition of CPE and environmental sampling was performed during a CPE outbreak between July and December 2018. FINDINGS: A total of 87 patients with CPE infection or colonization were identified in the cardiology units of the Asan Medical Centre. Diverse organisms were identified containing blakpc, blaNDM-1, blaVIM or blaIMP, blaOXA-48, and co-producing organisms. A case-control study indicated that using the sinks in the ward patient room bathroom for teeth brushing was associated with CPE acquisition (83% vs 30%; P=0.03). The environment was cultured and Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli was isolated from a water dispenser and New Delhi metallo-beta-lactamase (NDM) 1-producing Citrobacter freundii and Enterobacter cloacae from sinks in patient rooms. Pulsed-field gel electrophoresis (PFGE) analysis of KPC-producing E. coli from patients and the water dispenser in ICU and NDM-1-producing E. cloacae from the patient and sink drain showed the same pulsotypes. CONCLUSIONS: The water dispenser and sink drain were suspected as possible reservoirs of CPE in this outbreak. Close contacts with contaminated water such as tooth brushing were identified as risk factors for CPE acquisition. Education for the adequate use of the water environment system as well as the control of the hospital water environment should be implemented to prevent the CPE outbreaks.

Visceral obesity, but not central obesity, is associated with cardiac remodeling in subjects with suspected metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS. METHODS AND RESULTS: We studied 229 participants with suspected MetS. Visceral fat area (VFA) was measured by bioelectrical impedance analysis. Left ventricular (LV) mass index, early diastolic velocity of mitral annulus (e'), and LV global longitudinal strain (GLS) were measured by echocardiography. Subjects were categorized into high and low VFA group (VFAh and VFAl). MetS was more prevalent in the VFAh than in the VFAl (p = 0.004). The VFAh had a higher waist circumference (WC) than the VFAl (p < 0.001). LV mass index was higher, but e' and GLS were lower in the VFAh than in VFAl (all p < 0.05). VFA was well correlated with blood pressure, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein and adiponectin (all p < 0.05). VFA was correlated to LV mass index, e', and GLS (all p < 0.05) and was independently associated with GLS after adjustment for other risk factors, including WC (p = 0.005). CONCLUSIONS: Visceral obesity assessed by VFA was well correlated with parameters of MetS. Visceral obesity, but not central obesity measured by WC, was independently associated with structural and functional cardiac remodeling in subjects with suspected MetS. It suggests that visceral obesity should be considered as an important risk factor for cardiac damage in dysmetabolic subjects. TRIAL REGISTRATION: NCT02077530 (date of registration: November 1, 2013).

Clearance of carbapenemase-producing Enterobacteriaceae (CPE) carriage: a comparative study of NDM-1 and KPC CPE.

OBJECTIVES: The aim of this study was to compare clearance rates and related characteristics of patients carrying KPC-producing carbapenemase-producing Enterobacteriaceae (CPE) with those of patients carrying NDM-1-producing CPE. METHODS: From November 2010 to October 2016, consecutive patients whose clinical or surveillance cultures yielded CPE were prospectively identified and followed in a 2700-bed tertiary referral hospital. CPE control protocols included strict single-room isolation, contact precautions and weekly surveillance cultures. CPE clearance was defined as three or more consecutive CPE-negative cultures without relapse. We compared patients carrying NDM-1 CPE and KPC and those with and without clearance. The time to CPE clearance or discharge was assessed using the Kaplan-Meier method and NDM-1 CPE and KPC CPE groups were compared. RESULTS: A total of 147 patients carrying CPE, 106 with NDM-1 and 41 with KPC, were included in the study. At the time of hospital discharge, 12 of the 106 patients carrying NDM-1 CPE were clear of CPE, whereas none of the KPC CPE patients were (NDM-1, 11.3% (12/106) versus KPC, 0% (0/41), p 0.02). There was no significant association between CPE clearance and factors such as an immunocompromised condition, antibiotic usage, or species of colonizing organism. Among 40 patients who were readmitted, CPE non-clearance was significantly higher in patients carrying KPC CPE (NDM-1, 36.7% (11/30) versus KPC, 80.0% (8/10), p 0.03). CONCLUSIONS: Compared with NDM-1 CPE patients, patients carrying KPC CPE had a significantly lower probability of clearance during hospitalization. Furthermore, KPC CPE carriage persisted for a substantial period of time following patient discharge.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis.

BACKGROUND: Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness. METHODS: In total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children. RESULTS: Sputum TARC levels were significantly higher in children with asthma than in either children with EB (p=0.004) or the control subjects (p=0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p=0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC20 (the provocative concentration of methacholine causing a 20% decrease in the FEV1). CONCLUSION: Elevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation.

IgE cross-reactivity of peanut with walnut and soybean in children with food allergy.

BACKGROUND: Peanut allergies are common and can be life-threating for sensitised individuals. Peanut allergens share significant amino acid homology with those of other legumes and tree nuts, but their cross-reactivity still remains unclear. OBJECTIVE: We sought to determine the clinical significance of the cross-reactivity of peanut allergens with those of walnut and soybean. METHODS: Pooled sera from eight subjects with both peanut and walnut specific IgE were investigated in an inhibition test. After the sera were incubated with either peanut or walnut protein extracts, the quantity of IgE antibodies against the peanut and walnut was measured using an immunoCAP test. Likewise, pooled sera from 18 subjects with both peanut and soybean specific IgE antibodies were incubated with either peanut or soybean protein extracts and evaluated with a peanut and soybean immunoCAP test. SDS-PAGE and immunoblotting were also performed with peanut, walnut and soybean protein extracts and relevant sera. RESULTS: Peanut specific IgE was inhibited up to 20% and 26% by walnut and soybean protein extracts, respectively. In reverse, walnut and soybean specific IgE were inhibited up to 21% and 23% by peanut protein extracts, respectively. In the immunoblot analysis, pooled serum from the subjects with peanut specific IgE antibodies reacted with walnut protein extracts significantly. CONCLUSION: Although the clinical significance of the cross-reactivity of peanut specific IgE with walnut and soybean protein extracts has not been established, we believe that individuals who are allergic to peanuts need to be cautious about consuming walnuts and soybeans.

Tightening effects of high-intensity focused ultrasound on body skin and subdermal tissue: a pilot study.

BACKGROUND: High-intensity focused ultrasound (HIFU) has been introduced as a new treatment modality for skin tightening through application mainly to the face and neck. OBJECTIVES: This pilot study assessed the efficacy and safety of HIFU for body tightening in Asian females. METHODS: Six Asian female adults were enrolled in this pilot study. All subjects were treated with HIFU to the both cheek, upper arm, lower abdomen, thigh and calf using the following probes: 7 MHz, 1.5 mm focal depth; 2 MHz, 3.0 mm focal depth; 2 MHz, 4.5 mm focal depth; 2 MHz, 6.0 mm focal depth and 2 MHz, 9.0 mm focal depth. Three blinded independent dermatologists assessed results using the Investigator Global Aesthetic Improvement Scale (GAIS) using paired pre- and post-treatment (week 4) standardized photographs. Also, we evaluated skin elasticity at all treated sites using a cutometer. Participants used the subject GAIS to assess their clinical improvement after treatment and rated their pain using a visual analogue scale (VAS) immediately, 1 and 4 weeks after treatment. RESULTS: The three blinded evaluators judged all treated sites as showing clinical improvement 4 weeks after treatment. Skin elasticity measured via cutometer was significantly improved 4 weeks after treatment at all treated sites (P < 0.05). All patients scored themselves subjectively as more than 'improved' on the GAIS. Immediately after treatment the mean VAS score was 5.17 ± 2.48, but no pain was reported at weeks 1 and 4. No permanent adverse effects were observed during the follow-up period. CONCLUSION: For body tightening, we applied HIFU using transducers with a lower frequency and deep focal depth to effectively deliver ultrasound energy to skin tissues. HIFU appears to be a safe and effective treatment modality for dermal and subdermal tightening.

Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country.

Subspecies distribution and macrolide and fluoroquinolone resistance genetics of Mycobacterium abscessus in Korea.

BACKGROUND: Treating Mycobacterium abscessus infections with antimicrobials remains difficult, possibly due to drug resistance. OBJECTIVE: To investigate the subspecies distribution of M. abscessus and its correlation with antibiotic susceptibility and the genetics of antibiotic resistance, focusing on macrolides and fluoroquinolones, in the Republic of Korea. DESIGN: A total of 53 M. abscessus isolates were identified to the subspecies level by sequencing of hsp65 and erm(41). The minimal inhibitory concentrations (MICs) of clarithromycin (CLM) and ciprofloxacin (CFX) were determined using Sensititre™ RAPMYCO plates. The rrl, gyrA and gyrB genes were sequenced to elucidate the molecular mechanisms of macrolide and fluoroquinolone resistance. RESULTS: Isolates included 22 M. abscessus subsp. abscessus and 31 M. abscessus subsp. bolletii. erm(41) sequences showing subspecies-specific deletions and sequence variations in the 28th nucleotide were concordant with inducible CLM resistance; however, mutations in rrl were not detected. Low- and high-level CFX resistance was observed in respectively 19 (35.8%) and 10 (18.9%) of the 53 clinical isolates, regardless of subspecies. However, no non-synonymous mutations were detected in gyrA or gyrB. CONCLUSION: Sequencing of the erm gene and subspeciation of M. abscessus may be used to predict inducible macrolide susceptibility. Further studies of the relationship between specific mutations in gyrA or gyrB to MIC change are required.

Relationship between sputum clusterin levels and childhood asthma.

BACKGROUND: Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated. OBJECTIVES: (1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness. METHODS: This study included 170 children aged 5-18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay. RESULTS: Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = -0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters. CONCLUSIONS AND CLINICAL RELEVANCE: Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.

The role of interleukin-17 in mouse models of atopic dermatitis and contact dermatitis.

BACKGROUND: Atopic dermatitis (AD) and contact dermatitis (CD) are both T cell-mediated eczematous disorders. Interleukin (IL)-17, expressed by T helper (Th)17 cells, is involved in recruitment of inflammatory cells into AD and CD skin. AIM: In this study, we investigated whether IL-17 regulates immune dysregulation and affects skin barrier in oxazolone (OXA)-induced AD-like and CD-like disease models in mice, by comparing IL-17 null mutant (IL-17(-/-) ) vs. wild-type (WT) mouse strains in the models. METHODS: IL-17(-/-) and WT Balb/c mice were used for OXA induction of AD-like and CD-like skin diseases. Ear swelling was measured by a micrometer. Skin biopsies were obtained for RNA isolation and histology. Real-time quantitative PCR analysis was performed to quantify mRNA expression of Th2 cytokines. Skin permeability was measured by a vapometer, and structural changes in the skin were evaluated by electron and confocal microscopy. RESULTS: Both OXA-induced AD and CD responses were alleviated in IL-17(-/-) mice relative to WT, as demonstrated by reductions in ear swelling, inflammatory cell infiltration and levels of Th2 cytokines. These endpoints were used to characterize inflammatory dysregulation in both AD and CD models. Skin-barrier dysfunction, measured by increases in transepidermal water loss and dysfunction of lamellar bodies, and reductions in lipid distribution, were seen in both AD and CD in WT mice. In IL-17(-/-) mice, however, these responses were significantly diminished. CONCLUSIONS: The results indicate that the IL-17 gene may play a role in modulating immune dysregulation and affecting skin barrier in OXA-induced AD-like and CD-like skin disease models in the Balb/c mouse.