Frequency of azole resistance in clinical and environmental strains of Aspergillus fumigatus in Turkey: a multicentre study.

OBJECTIVES: Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Turkey. METHODS: Twenty-one centres participated in this study from 1 May 2018 to 1 October 2019. One participant from each centre was asked to collect environmental and clinical A. fumigatus isolates. Azole resistance was screened for using EUCAST agar screening methodology (EUCAST E.DEF 10.1) and was confirmed by the EUCAST E.DEF 9.3 reference microdilution method. Isolates with a phenotypic resistance pattern were sequenced for the cyp51A gene and microsatellite genotyping was used to determine the genetic relationships between the resistant strains. RESULTS: In total, resistance was found in 1.3% of the strains that were isolated from environmental samples and 3.3% of the strains that were isolated from clinical samples. Mutations in the cyp51A gene were detected in 9 (47.4%) of the 19 azole-resistant isolates, all of which were found to be TR34/L98H mutations. Microsatellite genotyping clearly differentiated the strains with the TR34/L98H mutation in the cyp51A gene from the strains with no mutation in this gene. CONCLUSIONS: The rate of observed azole resistance of A. fumigatus isolates was low in this study, but the fact that more than half of the examined strains had the wild-type cyp51A gene supports the idea that other mechanisms of resistance are gradually increasing.

Paliperidone palmitate use in pregnancy in a woman with schizophrenia.

Long-acting antipsychotic use in schizophrenia has become an advantage for treatment compliance and convenient administration of the drugs. There is no data on paliperidone palmitate (PP) use in pregnancy, which is the longest-acting (i.e., 1 month) atypical antipsychotic. In this case report, we aim to present a patient diagnosed with schizophrenia who had been using PP before and during her pregnancy until week 28 of gestation and gave birth to a male baby that weighed 3000 g at 39 weeks. As far as we know, this is the first case report on PP use during pregnancy.

Streptococcus mitis septic arthritis after leucocyte-rich platelet-rich plasma injection for the knee osteoarthritis: A case report.

A 62-year-old female patient having comorbidities of hypertension, hyperlipidemia, obesity, peptic ulcer, and bilateral Grade II knee osteoarthritis was admitted with a complaint of knee pain. An intra-articular leukocyte-rich platelet-rich plasma (LR-PRP) injection was administered to both knees after clinical and laboratory examinations. Three days later, the pain increased and synovial effusion developed in her left knee. The patient was diagnosed with Streptococcus mitis-induced septic arthritis. Clinical and laboratory improvement was obtained with immediate ceftriaxone treatment in addition to irrigation and debridement. This is the first case report in the literature describing septic arthritis developing after intra-articular injection LR-PRP injection.

Targeting IRE1 endoribonuclease activity alleviates cardiovascular lesions in a murine model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1ß pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the potential implication of ER stress in KD pathophysiology has not been investigated to our knowledge. We used human patient data and the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to characterize the impact of ER stress on the development of cardiovascular lesions. KD patient transcriptomics and single-cell RNA sequencing of the abdominal aorta from LCWE-injected mice revealed changes in the expression of ER stress genes. Alleviating ER stress genetically, by conditional deletion of inositol-requiring enzyme 1 (IRE1) in myeloid cells, or pharmacologically, by inhibition of IRE1 endoribonuclease (RNase) activity, led to significant reduction of LCWE-induced cardiovascular lesion formation as well as reduced caspase-1 activity and IL-1ß secretion. These results demonstrate the causal relationship of ER stress to KD pathogenesis and highlight IRE1 RNase activity as a potential new therapeutic target.

Complete Genome Sequences of Cluster A6 and Cluster G1 Mycobacterium smegmatis Phages Hoot and Jolene.

We present the complete genome sequences of Mycobacterium smegmatis phages Hoot and Jolene, isolated in Las Vegas, NV. The phages were isolated and annotated by students enrolled in an undergraduate research course at the University of Nevada, Las Vegas. Hoot is a cluster A6 mycobacteriophage, while Jolene is in cluster G1.

A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro.

We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif at its polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superantigenic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by interfering with the proteolytic activity of cell proteases (furin and TMPRSS2). The high affinity of 6D3 for this site originates from a polyacidic segment at its heavy chain CDR2. The study points to the potential utility of 6D3 for possibly treating COVID-19, MIS-C, or common colds caused by human coronaviruses that also possess a furin-like cleavage site.

Autophagy-mitophagy induction attenuates cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Murine and human data suggest that the NLRP3-IL-1ß pathway is the main driver of KD pathophysiology. NLRP3 can be activated during defective autophagy/mitophagy. We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to examine the role of autophagy/mitophagy on cardiovascular lesion development. LCWE-injected mice had impaired autophagy/mitophagy and increased levels of ROS in cardiovascular lesions, together with increased systemic 8-OHdG release. Enhanced autophagic flux significantly reduced cardiovascular lesions in LCWE-injected mice, whereas autophagy blockade increased inflammation. Vascular smooth muscle cell-specific deletion of Atg16l1 and global Parkin-/- significantly increased disease formation, supporting the importance of autophagy/mitophagy in this model. Ogg1-/- mice had significantly increased lesions with increased NLRP3 activity, whereas treatment with MitoQ reduced vascular tissue inflammation, ROS production, and systemic 8-OHdG release. Treatment with MN58b or Metformin (increasing AMPK and reducing ROS) resulted in decreased cardiovascular lesions. Our results demonstrate that impaired autophagy/mitophagy and ROS-dependent damage exacerbate the development of murine KD vasculitis. This pathway can be efficiently targeted to reduce disease severity. These findings enhance our understanding of KD pathogenesis and identify potentially novel therapeutic avenues for KD treatment.

A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro.

We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19, MIS-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin-like cleavage site.

Comparison of Three Different New Bipolar Energy Modalities and Classic Bipolar in Vivo for Tissue Thermal Spread.

OBJECTIVE: The aim of this study was to compare three different new bipolar energy modalities and classic bipolar in vivo for tissue thermal spread. MATERIAL AND METHOD: This prospective, randomized, single-blind study was conducted between Septemsber 2012 and July 2013. Eighteen patients aged 40-65 years undergoing hysterectomy and bilateral salpingectomy for benign etiology were included in the study. Before the hysterectomy operation began, it was marked nearly distal third cm started from uterine corn and proximal close third cm started from fimbrial bottoms by visualizing both fallopian tubes. The surgery was performed using one 5 mm applicator of PlasmaKinetics™, EnSeal®, LigaSure™ or classic bipolar energy modality. The time each device was used was standardized as the minimum time of the audible warning of the device for tissue impedance and as tissue vaporization on classic bipolar. Tissues were dyed by both H&E and Masson's Trichrome in the pathology laboratory. Thermal spread was compared. RESULTS: Evaluation of the damage on the uterine tubes by each device used revealed that LigaSure™ was associated with increased thermal injury compared to PlasmaKinetics™ (p=0.007). Apart from PlasmaKineticsTM (p=0.022), there was no statistically significant difference between the three devices in terms of thermal damage spread in the distal and proximal fallopian tubes. CONCLUSION: To reduce lateral thermal damage, Plasmakinetics™ may be preferable to Ligasure™ among the three different new bipolar energy modalities.

Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection.

BACKGROUND: Little is known about factors associated with carbapenem-resistant Klebsiella pneumoniae infections in pediatric patients, who are initally colonized with carbapenem-resistant Klebsiella pneumoniae. MATERIALS AND METHODS: A retrospective case-control study was conducted involving pediatric and neonatal intensive care units throughout a five-year period (January 2010-December 2014). Clinical and microbiological data were extracted from Hospital Infection Control Committee reports and patients' medical records. Risk factors were assessed in carbapenem-resistant Klebsiella pneumoniae colonized patients who developed subsequent systemic infection (cases) and compared to carbapenem-resistant Klebsiella pneumoniae colonized patients who did not develop infection (controls). RESULTS: Throughout the study period, 2.6% of patients admitted to neonatal intensive care units and 3.6% of patients admitted to pediatric intensive care units had become colonized with carbapenem-resistant Klebsiella pneumoniae. After a mean of 10.6±1.9 days (median: 7 days, range: 2-38 days) following detection of colonization, 39.0% of the carbapenem-resistant Klebsiella pneumoniae colonized patients in pediatric intensive care units and 18.1% of carbapenem-resistant Klebsiella pneumoniae colonized patients in neonatal intensive care units developed systemic carbapenem-resistant Klebsiella pneumoniae infection. Types of systemic carbapenem-resistant Klebsiella pneumoniae infections included bacteremia (n=15, 62.5%), ventilator-associated pneumonia (n=4, 16.6%), ventriculitis (n=2, 8.3%), intraabdominal infections (n=2, 8.3%), and urinary tract infection (n=1, 4.1%). A logistic regression model including parameters found significant in univariate analysis of carbapenem resistant Klebsiella pneumoniae colonization and carbapenem resistant Klebsiella pneumoniae infection groups revealed underlying metabolic disease (OR: 10.1; 95% CI: 2.7-37.2), previous carbapenem use (OR: 10.1; 95% CI: 2.2-40.1), neutropenia (OR: 13.8; 95% CI: 3.1-61.0) and previous surgical procedure (OR: 7.4; 95% CI: 1.9-28.5) as independent risk factors for carbapenem-resistant Klebsiella pneumoniae infection in patients colonized with carbapenem-resistant Klebsiella pneumoniae. Out of 24 patients with carbapenem resistant Klebsiella pneumoniae infection, 4 (16.6%) died of carbapenem-resistant Klebsiella pneumoniae sepsis. CONCLUSION: Asymptomatic colonization with carbapenem-resistant Klebsiella pneumoniae in intensive care units of pediatric departments should alert health care providers about forthcoming carbapenem-resistant Klebsiella pneumoniae infection. Those carbapenem-resistant Klebsiella pneumoniae colonized patients at risk of developing infection due to carbapenem-resistant Klebsiella pneumoniae may be targeted for interventions to reduce subsequent infection occurence and also for timely initiation of empirical carbapenem-resistant Klebsiella pneumoniae active treatment, when necessary.

Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection.

OBJECTIVE: To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. MATERIALS AND METHODS: Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. RESULTS: Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. CONCLUSION: VRE colonization has important consequences in pediatric cancer patients.

Impact of vancomycin-resistant enterococci colonization in critically ill pediatric patients.

BACKGROUND: We aimed to determine the frequency of vancomycin-resistant enterococci (VRE) infection occurrence in previously VRE-colonized children in a pediatric intensive care unit (PICU) and to identify associated risk factors. METHODS: Infection control nurses have performed prospective surveillance of health care-associated infections and rectal VRE carriage in PICUs from January 2010-December 2014. This database was reviewed to obtain information about VRE-colonized and subsequently infected patients. A case-control study was performed to identify risk factors associated with VRE infection development in previously VRE-colonized patients. RESULTS: Out of 1,134 patients admitted to the PICU, 108 (9.5%) were found to be colonized with VRE throughout the study period. Systemic VRE infections developed in 11 VRE-colonized patients (10.2%), and these included primary bloodstream infection (n = 6), urinary tract infection (n = 3), meningitis and bloodstream infection (n = 1), and meningitis (n = 1). Logistic regression analysis indicated long hospital stay (≥30 days) and glycopeptide use after detection of VRE colonization as risk factors for developing VRE infection in VRE-colonized patients (odds ratio [OR], 5.76; 95% confidence interval [CI], 1.6-15.8; P = .017 and OR, 12.8; 95% CI, 1.9-26.6; P = .012, respectively). CONCLUSIONS: VRE colonization has important consequences in pediatric critically ill patients. Strict infection control measures should be implemented to prevent VRE colonization and thereby VRE infections. Furthermore, irrational antibiotic use and particularly glycopeptide use in VRE-colonized patients should be restricted.