Showing papers in "Journal of Microbiology Immunology and Infection in 2016"
TL;DR: Insight is provided into the development of new antimicrobial agents along with synergistic enhancement of the antibacterial mechanism against clinical bacteria as well as the synergistic effect of bio(AgNPs) with various commercially available antibiotics.
Abstract: Background/Purpose In this study, an acidophilic actinobacteria strain was used as a novel reducing agent for a single-step synthesis of nanostructure silver particles. We used a Streptacidiphilus durhamensis HGG16n isolate for efficient synthesis of bioactive silver nanoparticles [bio(AgNPs)] in an inexpensive, eco-friendly, and nontoxic manner. The obtained bio(AgNPs) exhibited unique physicochemical and biochemical properties. Methods Structural, morphological, and optical properties of the synthesized biocolloids were characterized by spectroscopy, dynamic light scattering, and electron microscopy approaches. The antimicrobial activity was evaluated using the well- and disc-diffusion methods. Results The obtained crystalline structure and stable biosynthesized silver nanoparticles ranged in size from 8 nm to 48 nm and were mostly spherical in shape. Antimicrobial assays of the silver nanoparticles against pathogenic bacteria showed the highest antimicrobial activity against Pseudomonas aeruginosa , Staphylococcus aureus , and Proteus mirabilis, followed by Escherichia coli , Klebsiella pneumoniae , and Bacillus subtilis . Moreover, the synergistic effect of bio(AgNPs) with various commercially available antibiotics was also evaluated. Conclusion These results provide insight into the development of new antimicrobial agents along with synergistic enhancement of the antibacterial mechanism against clinical bacteria.
157 citations
TL;DR: The results demonstrate that silver nanoparticles have good antifungal activity against T. asahii, and based on electron microscopy observations,silver nanoparticles may inhibit the growth of T.Asahii by permeating the fungal cell and damaging the cell wall and cellular components.
Abstract: Background/Purpose Silver nanoparticles are receiving increasing attention in biomedical applications. This study aims at evaluating the antifungal properties of silver nanoparticles against the pathogenic fungus Trichosporon asahii . Methods The growth of T. asahii on potato dextrose agar medium containing different concentrations of silver nanoparticles was examined and the antifungal effect was evaluated using minimum inhibitory concentration. Scanning and transmission electron microscopy were also used to investigate the antifungal effect of silver nanoparticles on T. asahii . Results Silver nanoparticles had a significant inhibitory effect on the growth of T. asahii . The minimum inhibitory concentration of silver nanoparticles against T. asahii was 0.5 μg/mL, which was lower than amphotericin B, 5-flucytosine, caspofungin, terbinafine, fluconazole, and itraconazole and higher than voriconazole. Silver nanoparticles obviously damaged the cell wall, cell membrane, mitochondria, chromatin, and ribosome. Conclusion Our results demonstrate that silver nanoparticles have good antifungal activity against T. asahii . Based on our electron microscopy observations, silver nanoparticles may inhibit the growth of T. asahii by permeating the fungal cell and damaging the cell wall and cellular components.
146 citations
TL;DR: Oral administrations of Lactobacillus rhamnosus GG had an anti-inflammatory effect on OVA-induced airway inflammation and might be an additional or supplementary therapy for allergic airway diseases.
Abstract: Background Asthma is a common allergic disease. In previous studies, probiotics improved the balance of intestinal microbes, reduced inflammation, and promoted mucosal tolerance. This study investigated whether oral administrations of Lactobacillus rhamnosus GG (LGG) inhibited allergen (ovalbumin or OVA)-induced airway inflammation in a mouse asthma model. Methods The allergy/asthma animal model in this study was sensitization with OVA. After intranasal challenge with OVA, the airway inflammation and hyper-responsiveness were determined by a Buxco system, bronchoalveolar lavage fluid analysis with Liu stain, and enzyme-linked immunosorbent assay. Histopathologic changes in the lung were detected by hematoxylin and eosin staining and immunohistochemistry staining. Results Both pre- and post-treatment with LGG suppressed the airway hyper-responsiveness to methacholine and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid and serum compared with the OVA-sensitized mice. In addition, LGG reduced OVA-specific IgE levels in serum. Oral LGG decreased matrix metalloproteinase 9 expression in lung tissue and inhibited inflammatory cell infiltration. Conclusion LGG had an anti-inflammatory effect on OVA-induced airway inflammation and might be an additional or supplementary therapy for allergic airway diseases.
92 citations
TL;DR: The anti-QS nature of C. asiatica herb can be further exploited for the formulation of drugs targeting bacterial infections where pathogenicity is mediated through QS.
Abstract: Background/Purpose: Inhibition of quorum sensing (QS), a cell-density dependent regulation of gene expression in bacteria by autoinducers is an attractive strategy for the development of antipathogenic agents. Methods: Inthisstudy,theanti-QSactivityoftheethanolicextractofthetraditionalherbCentella asiatica was investigated by the biosensor bioassay usingChromobacterium violaceumCV026. The effect ofethyl acetatefraction(CEA) from thebioassay-guided fractionation ofethanol extract on QS-regulated violacein production in C. violaceum ATCC12472 and pyocyanin production, proteolyticandelastolyticactivities,swarmingmotility,andbiofilmformationinPseudomonasaeruginosa PAO1 were evaluated. Possible mechanism of QS-inhibitory action on autoinducer activity was
91 citations
TL;DR: It is evident that innovative research is required to exploit the antimicrobial properties of honey for clinical use and to determine the efficacy of honey in the treatment of a range of skin disorders with a microbiological etiology.
Abstract: Resistance of pathogenic microorganisms to antibiotics is a serious global health concern. In this review, research investigating the antimicrobial properties of honeys from around the world against skin relevant microbes is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent microbicidal activity against dermatologically important microbes. Moreover, in vitro studies have shown that honey can reduce microbial pathogenicity as well as reverse antimicrobial resistance. Studies investigating the antimicrobial properties of honey in vivo have been more controversial. It is evident that innovative research is required to exploit the antimicrobial properties of honey for clinical use and to determine the efficacy of honey in the treatment of a range of skin disorders with a microbiological etiology.
88 citations
TL;DR: In Taiwan, the prevalence of CRPA and carriage of carbapenemase-producing genes was high, however, carbAPenem resistance did not play a role in the mortality of patients with P. aeruginosa infections.
Abstract: Background The prevalence and clinical impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) is unclear in Taiwan. We aim to clarify these clinical issues by using data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program. Methods Patients from five hospitals with their P. aeruginosa isolates collected by TSAR II-VII (2000–2010) program were considered as the potential study population. All patients with CRPA were enrolled as case patients. Patients with carbapenem-susceptible P. aeruginosa were randomly selected in a 1:1 ratio to case patients as control patients. CRPA isolates were tested for the presence of carbapenemase-producing genes. The clinical data were collected to identify risk factors for CRPA carriage and mortality of P. aeruginosa infection. Results The overall prevalence of CRPA was 10.2% (349/3408), which increased significantly by the TSAR period ( p = 0.007). Among the 164 enrolled patients, the risk factor for carrying CRPA was previous fluoroquinolone exposure ( p = 0.004). The risk factors for mortality among 80 patients with infection by P. aeruginosa included: intensive care unit (ICU) setting, receipt of antifungal therapy, and presence of invasive devices ( p = 0.001, 0.010, and 0.017; respectively). Carbapenem resistance did not play a role. Among the 82 CRPA isolates enrolled in this study, 15 isolates were found to carry carbapenemase-producing genes. Conclusion In Taiwan, the prevalence of CRPA and carriage of carbapenemase-producing genes was high. However, carbapenem resistance did not play a role in the mortality of patients with P. aeruginosa infections.
72 citations
TL;DR: The clinical outcomes of pyogenic liver abscess treated with cefazolin were comparable to those treated by extended-spectrum cephalosporins, and Extended-spectrums cep Halosporin should be used for severe complications, such as meningitis and endophthalmitis.
Abstract: Background The epidemiology of pyogenic liver abscess continues to change and the issue of antimicrobial therapy is controversial. This study investigated the epidemiology and clinical outcomes of antimicrobial therapy. Methods The annual incidence rates, demographic data, underlying diseases, complications, length of stay, mortality rates, and antimicrobial therapy were analyzed using the data retrieved from the Longitudinal Health Insurance Database 2000, Taiwan, from 2000 to 2011. Results The annual incidence of pyogenic liver abscess for all age groups increased gradually in Taiwan from 10.83 per 100,000 person-years in 2000 to 15.45 per 100,000 person-years in 2011. Pyogenic liver abscess occurred more commonly in patients with male sex, of older age (>50 years), and lower family income. Among the 1522 adult patients with pyogenic liver abscess, 537 (35.3%) patients had diabetes mellitus, 165 (10.8%) patients had complications, 234 (15.4%) patients received mechanical ventilation, and 361 (23.7%) patients had a stay in intensive care; the mortality rate was 8.2% (125/1522). There were 426 (28%) patients treated with cefazolin and 158 (10.4%) patients treated with extended-spectrum cephalosporins. There were no statistically significant differences in the length of stay and mortality rates between these two groups (20.2 days vs. 23.1 days; and 7.5% vs. 10.1%, respectively). Conclusion The clinical outcomes of pyogenic liver abscess treated with cefazolin were comparable to those treated by extended-spectrum cephalosporins. Extended-spectrum cephalosporins should be used for severe complications, such as meningitis and endophthalmitis. Further surveillance of epidemiology and cohort analysis of antimicrobial therapy are important.
72 citations
TL;DR: This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics, and found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples.
Abstract: Background/Purpose Subgingival microorganisms are potentially associated with periodontal diseases. However, the correlation between the variance in the periodontal microbiome and the prevalence and severity of periodontitis remains unclear. The aim of this study was to determine the subgingival microbiota in Taiwanese individuals with severe chronic periodontitis (SP). Methods The composition of the subgingival microbiota in healthy and diseased individuals was compared using a 16S rRNA metagenomic approach and quantitative polymerase chain reaction (qPCR). A total of 20 samples, including 10 from healthy individuals and 10 from SP patients, were analyzed. Results We found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples. Cluster analysis by principal component analysis and heat map showed that the bacterial communities were different in the two groups. Streptococcus dominated across all the healthy samples, whereas Prevotella , Porphyromonas , and Treponema were highly abundant across all diseased samples. At least 13 bacterial genera were conserved among all the samples. Only eight genera, including Lautropia , Parvimonas , Actinomyces , Capnocytophaga , Paludibacter , Streptococcus , Haemophilus , and Corynebacterium , were significantly enriched in the healthy group, and six genera, including Porphyromonas , Treponema , Tannerella , Aggregatibacter , Peptostreptococcus , and Filifactor , were significantly enriched in the diseased group. Furthermore, a trend of abundance of bacteria at the species level measured by qPCR in all samples was consistent with the 16S rRNA metagenomics results. Conclusion This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics.
64 citations
TL;DR: These isolates were genetically diverse in pulsotype analysis, lacked toxin genes of human pathogenic E. coli and carried mostly the prevalent virulence genes fimH, papGII, and α-hemolysin.
Abstract: Background/Purpose Escherichia coli is a common pathogen to cause clinical and subclinical mastitis in cows. A total of 57 E. coli isolates from raw milk from cows were characterized genetically and biochemically. Methods Extended-spectrum β-lactamase (ESBL) genes, the mechanism for fluoroquinolone resistance, and variations in virulence genes and genomes of these E. coli isolates were investigated by the antimicrobial susceptibility test, simplex and multiplex polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE). Results All E. coli isolates were resistant to cloxacillin (100%) and to a lesser extent (50%) to tetracycline, neomycin, gentamycin, ampicillin, ceftriaxone, cefotaxime (CTX), and ceftazidime (CAZ). Nearly 70% of the isolates were resistant to at least two antimicrobials and 28.1% carried AmpA and AmpC genes simultaneously. The predominant bla gene was bla TEM , followed by bla CMY , bla CTX , bla SHV , and bla DHA. Among the six (10.5%) ESBL-producing E. coli carrying bla CTX-M15 , bla CTX-M55 , or bla CTX-M14 , two isolates 31 of ST410 in the ST23 complex and 58 of ST167 in the ST10 complex were also resistant to ciprofloxacin, enrofloxacin, and levofloxacin, with mutations at codon 83 from serine to leucine and codon 87 from aspartic acid to asparagine in GyrA and at codon 80 from serine to isoleucine in ParC. These isolates were genetically diverse in pulsotype analysis, lacked toxin genes of human pathogenic E. coli and carried mostly the prevalent virulence genes fimH , papGII , and α-hemolysin . Conclusion Lacking virulence genes examined, genetic diverse E. coli isolates are unrelated to human pathogenic E. coli . Enhancing sanitation in milk processing and transportation is needed to eliminate multidrug-resistant (MDR), fluoroquinolone-resistant, and ESBL-producing E. coli isolates.
52 citations
TL;DR: Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.
Abstract: Background/Purpose Identification of risks of mortality for carbapenem-resistant Acinetobacter baumannii (CRAB), with early implementation of an appropriate therapy, is crucial for the patients' outcome. The aim of this study was to survey mortality risk factors in 182 patients with CRAB bacteremia in a medical center in Taiwan. Methods A total of 182 isolates of CRAB bacteremia were collected from 2009 to 2012 in Mackay Memorial Hospital, Taipei, Taiwan These isolates were identified by using the genotypic method. Risk of attributable mortality analysis was carried out with a Cox proportional hazards model. Results The 182 CRAB isolates belonged to 38 different pulsotypes. The attributable mortality rate of the 182 patients was 58.24%. The risk factors for attributable mortality included intensive care unit stay [hazard ratio (HR): 2.27; p = 0.011], an Acute Physiology and Chronic Health Evaluation II score of >20 (HR: 2.19; p p p = 0.011). The appropriateness of antimicrobial therapy was 18.87% (20/106) in the mortality group versus 88.16% (67/76) in the survivor group ( p Conclusion The risk factors for mortality for CRAB included intensive care unit stay, a high Acute Physiology and Chronic Health Evaluation II score, respiratory tract as the origin of bacteremia, and previous use of ceftriaxone. Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.
45 citations
TL;DR: This review focuses on the factors associated with the genetic polymorphisms of KD and the pharmacogenomics of the response to treatment in patients with intravenous immunoglobulin resistance.
Abstract: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and it is therefore worth examining the multifactorial interaction of genes and environmental factors Targeted genetic association and genome-wide association studies have helped to provide a better understanding of KD from infection to the immune-related response Findings in the past decade have contributed to a major breakthrough in the genetics of KD, with the identification of several genomic regions linked to the pathogenesis of KD, including ITPKC , CD40, BLK , and FCGR2A This review focuses on the factors associated with the genetic polymorphisms of KD and the pharmacogenomics of the response to treatment in patients with intravenous immunoglobulin resistance
TL;DR: These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection.
Abstract: Background Influenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection. Methods Mice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined. Results Because of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group. Conclusion These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection.
TL;DR: The results suggest that risk group stratification prior to HSCT and monitoring of IFI in patients with severe GVHD receiving high-dose steroids is mandatory to reduce the mortality and morbidity of post-HSCT IFI, especially in those with prior history of I FI.
Abstract: Background To investigate the incidence and risk factors for the occurrence of proven or probable invasive fungal infection (IFI) in adult patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Methods We retrospectively analyzed 421 patients undergoing HSCT between 2002 and 2013 in our hospital. The risk factors for the occurrence of IFI were analyzed using Cox regression models. Results Thirty-one patients with the median age of 42 years (range, 19–60 years) developed IFI after HSCT. The post-HSCT IFI incidence was 7.4% and median time from HSCT to the diagnosis of IFI was 139 days (range, 2–1809 days). Of the pretransplant factors, European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 ( p = 0.001) and prior history of IFI ( p = 0.006) or type 2 diabetes mellitus (DM; p = 0.042) were the significant predictors for post-HSCT IFI in univariate analyses. In multivariate analysis, EBMT risk score > 2 ( p = 0.015) and prior history of IFI ( p = 0.006) retained significance. Of the post-transplant factors, acute graft-versus-disease (GVHD) overall Grade III–IV ( p p = 0.002), development of post-transplant lymphoproliferative disorders ( p = 0.005), and the use of high-dose steroids ( p p p = 0.045) retained significance. Conclusion These results suggest that risk group stratification prior to HSCT and monitoring of IFI in patients with severe GVHD receiving high-dose steroids is mandatory to reduce the mortality and morbidity of post-HSCT IFI, especially in those with prior history of IFI.
TL;DR: The determination of antimicrobial susceptibility of these mycoplasma species is often crucial for optimal antimicrobial therapy of infected outpatients.
Abstract: Purpose The aim of this study was to estimate the prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis among female outpatients treated for genital infection at a Chinese hospital from January 1, 2009 to December 31, 2013. Methods Samples from 6051 female outpatients were analyzed using Mycoplasma Identification and Antimicrobial Susceptibility Testing (ID/AST). Results The overall prevalence of U. urealyticum was higher than the prevalence of single M. hominis infection (31.2% vs 0.7%) and coinfections (31.2% vs. 1.9%). The percentage of U. urealyticum and/or M. hominis detected in the 30–39 year age group was greater than in the other age groups. More than 94.6% of the U. urealyticum isolates, 100% of the M. hominis isolates, and 84.3% of the isolates from coinfections were susceptible to doxycycline, minocycline, and tetracycline. More than 69.2% of the U. urealyticum isolates were susceptible to azithromycin, erythromycin, clarithromycin, and roxithromycin, but > 95.6% of the M. hominis isolates and 89.6% of the isolates from coinfections were resistant to these antibiotics. Acetylspiramycin, sparfloxacin, levofloxacin, ciprofloxacin, and ofloxacin were inactive against more than one-half of the isolates. More than 75.6% of the M. hominis isolates were susceptible to spectinomycin, but > 87.1% of the U. urealyticum and 93.3% of the coinfection isolates were resistant to this antibiotic. Isolates from three coinfections were completely resistant to the 14 antibiotics. Conclusion The determination of antimicrobial susceptibility of these mycoplasma species is often crucial for optimal antimicrobial therapy of infected outpatients.
TL;DR: A rare case of Aggregatibacter aphrophilus brain abscess of odontogenic origin in a 6-year-old previously healthy boy, who had close contact with a pet dog, who was the most likely source of the infecting organism, which colonized the patient's oral cavity.
Abstract: We report on a rare case of Aggregatibacter aphrophilus brain abscess of odontogenic origin in a 6-year-old previously healthy boy, who had close contact with a pet dog. The poodle was the most likely source of the infecting organism, which subsequently colonized the patient's oral cavity. The abscess was surgically removed and he recovered completely after prolonged antibiotic treatment with meropenem. We also review the relevant medical literature on A. aphrophilus pediatric brain abscesses.
TL;DR: This interhospital comparison suggested that hospital-wide preauthorization program is the most effective to reduce key gram-negative bacilli resistance, with the exception of carbapenem-resistant A. baumannii.
Abstract: Background: The effects of various antimicrobial stewardship programs (ASPs) on both antibiotic consumption and resistance among different hospitals within the same insur- ance system have rarely been investigated. Methods: This 6-year retrospective study included three medical centers with similar facilities and infection control measures in Taiwan. These hospitals used different types of ASPs: one had a hospital-wide preauthorization requirement by infectious diseases physicians for all broad-spectrum antibiotics, covering all intensive care units; the second used the same
TL;DR: Cholesterol glucosylation by H. pylori interferes with phagosome trafficking via a lipid-raft and PI3K-dependent manner, which retards engulfment of bacteria for prolonged intracellular survival of H.pylori.
Abstract: Background/Purpose Helicobacter pylori colonizes the human stomach and contributes to chronic inflammation of the gastric mucosa. H. pylori persistence occurs because of insufficient eradication by phagocytic cells. A key factor of H. pylori , cholesterol-α-glucosyltransferase encoded by capJ that extracts host cholesterol and converts it to cholesteryl glucosides, is important to evade host immunity. Here, we examined whether phagocytic trafficking in macrophages was perturbed by capJ- carrying H. pylori. Methods J774A.1 cells were infected with H. pylori at a multiplicity of infection of 50. Live-cell imaging and confocal microscopic analysis were applied to monitor the phagocytic trafficking events. The viability of H. pylori inside macrophages was determined by using gentamicin colony-forming unit assay. The phagocytic routes were characterized by using trafficking-intervention compounds. Results Wild type (WT) H. pylori exhibited more delayed entry into macrophages and also arrested phagosome maturation more than did capJ knockout mutant. Pretreatment of genistein and LY294002 prior to H. pylori infection reduced the internalization of WT but not capJ -knockout H. pylori in macrophages. Conclusion Cholesterol glucosylation by H. pylori interferes with phagosome trafficking via a lipid-raft and PI3K-dependent manner, which retards engulfment of bacteria for prolonged intracellular survival of H. pylori .
TL;DR: The potential use of kanuka and manuka extracts as pharmaceutical antibiotics, medical cosmetology agents, and food supplements are confirmed and indicate that the potent antimicroorganism and anti-inflammation properties of kanukas make them strong candidates for use in treating infections and immune-related disease.
Abstract: Background: Diseases caused by infectious and inflammatory microorganisms are among the most common and most severe nosocomial diseases worldwide. Therefore, developing effective agents for treating these illnesses is critical. In this study, essential oils from two tea tree species, kanuka (Kunzea ericoides) and manuka (Leptospermum scoparium), were evaluated for use in treating diseases and inflammation caused by microorganism infection. Methods: Isolates of clinically common bacteria and fungi were obtained from American Type Culture Collection and from Kaohsiung Veterans General Hospital. Minimum inhibitory concentrations for Trichosporon mucoides, Malassezia furfur, Candida albicans, and Candida tropicalis were determined by the broth microdilution method with Sabouraud dextrose broth. The
TL;DR: Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimu may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines.
Abstract: Background Calcineurin inhibitors (CNIs) exhibit remarkable efficacy in atopic dermatitis (AD) Tacrolimus, one type of CNI, is prevalently used to treat AD AD is a chronic inflammatory disease that exhibits predominant infiltration of T-helper type 2 (Th2) cell in the acute phase and a mixed Th1 and Th0 cell pattern in chronic lesions Cytokines such as tumor necrosis factor-α (TNF-α), Th2-related chemokines [eg, macrophage-derived chemokine (MDC)/CCL22 and I-309/CCL1], Th1-related chemokines [eg, interferon γ-induced protein 10 (IP-10)/CXCL10], and neutrophil chemoattractant growth-related oncogene-α (GRO-α)/CXCL1 are involved in the pathogenesis of AD However, whether tacrolimus modulates the expression of AD-associated cytokines and chemokines remains unknown The intracellular mechanisms of tacrolimus are also unclear Methods Human monocytic cell line THP-1 cells were pretreated with tacrolimus and stimulated with lipopolysaccharide (LPS) The MDC, I-309, IP-10, GRO-α, and TNF-α concentrations of the cell supernatants were measured using enzyme-linked immunosorbent assay Intracellular signaling was investigated using the Western blot analysis Results Tacrolimus suppressed the expression of MDC, IP-10, I-309, GRO-α, and TNF-α in LPS-stimulated THP-1 cells in a dose- and time-dependent manner All three mitogen-activated protein kinase (MAPK) inhibitors and the nuclear factor-κB inhibitor suppressed LPS-induced MDC, I-309, and TNF-α expressions in THP-1 cells Only MAPK inhibitors suppressed LPS-induced expression of IP-10 and GRO-α Tacrolimus suppressed the LPS-induced phosphorylation of MAPK-extracellular signal-related kinase (ERK) Conclusion Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimus may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines
TL;DR: ESBL-producing bacteremic pneumonia, especially health-care-associated infections, often occurred in adults with comorbidities, and Appropriate empirical therapy was associated with a favorable outcome.
Abstract: Background Clinical information about bacteremic pneumonia caused by extended-spectrum beta-lactamase (ESBL)-producing organism is limited. Methods A retrospective study was conducted at two medical centers in Taiwan. From May 2002 to August 2010, clinical information and outcome of adults with bacteremic pneumonia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae were analyzed. The primary outcome is the 30-day mortality. Results A total of 111 patients with bacteremic pneumonia caused by E. coli (37 patients, 33.3%) and K. pneumoniae (74, 66.7%) were identified. Their mean age was 69.2 years and 51.4% were male patients. Fifty-seven (51.3%) episodes were classified as hospital-acquired infections, 19 (17.1%) as health-care-associated infections, and four (3.6%) as community-acquired infections. Fifty-one (45.9%) patients received appropriate empiric antimicrobial therapy. The 30-day mortality rate was 40.5% (45 patients). In the multivariate analysis, several independent risk factors, including rapidly fatal underlying disease [odds ratio (OR), 5.75; 95% confidence interval (CI), 1.54–21.48; p = 0.009], severe sepsis (OR, 4.84; 95% CI, 1.55–15.14; p = 0.007), critical illness (OR, 4.28; 95% CI, 1.35–13.57; p = 0.013), and receipt of appropriate empirical therapy (OR, 0.19; 95% CI, 0.07–0.55; p = 0.002), were associated with 30-day mortality. The survival analysis consistently found that individuals with appropriate empiric therapy had a higher survival rate (log-rank test, p Conclusion ESBL-producing bacteremic pneumonia, especially health-care-associated infections, often occurred in adults with comorbidities. Appropriate empirical therapy was associated with a favorable outcome.
TL;DR: EspB inhibits autophagosome formation in murine macrophages, at least in part by downregulating IFN-γ receptor 1 expression, and should be considered a relevant factor in the pathogenesis of mycobacterial infections in humans.
Abstract: Background Mycobacterium tuberculosis (Mtb) persists within immature phagosomes by preventing their maturation into phagolysosomes. Although the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion-associated protein B (EspB) of Mtb is strongly linked to immunogenicity and virulence of this organism, its mechanism of action remains largely unclear. This study aimed to investigate EspB effects on autophagy in murine ANA-1 macrophage cells. Methods EspB gene was amplified by polymerase chain reaction from Mtb H37Rv genomic DNA to express recombinant EspB protein. Levels of autophagic markers, including Microtubule-associated protein 1 light chain 3 beta (LC3B-I and -II), phosphorylated signal transducer and activator of transcription (STAT)1 and total STAT1 in ANA-1 cells treated with EspB proteins were assessed by Western blotting. In addition, autophagic vacuoles were detected by fluorescence microscopy. Finally, IFN-γR1 expression was evaluated by semiquantitative reverse transcriptase polymerase chain reaction and flow cytometry. Results EspB gene was expressed in Escherichia coli cells to yield a soluble N-terminal glutatione S-transferase tag fusion protein used in subsequent experiments. Preincubation with EspB significantly suppressed autophagosome formation and LC3B expression induced by interferon (IFN)-γ stimulation, in a dose-dependent manner. These results were confirmed by the reduced incorporation of monodansylcadaverine, a marker for the acidic compartment of autolysosomes, after treatment with EspB. Interestingly, we found that IFN-γ receptor 1 mRNA and protein levels were decreased in EspB-stimulated ANA-1 cells in comparison with untreated cells. Finally, EspB protein also inhibited IFN-γ-activated STAT1 phosphorylation, thereby downmodulating macrophage responsiveness to IFN-γ. Conclusion EspB inhibits autophagosome formation in murine macrophages, at least in part by downregulating IFN-γ receptor 1 expression. Overall, EspB should be considered a relevant factor in the pathogenesis of mycobacterial infections in humans.
TL;DR: Parenteral nutrition was a significant and independent risk of late-onset neonatal sepsis and should be considered when implementing early parenterals nutrition in NICUs.
Abstract: Background Infants in a neonatal intensive care unit (NICU) have a higher incidence of bloodstream infections (BSIs) than any other pediatric or adult population. The predisposing factors have not been comprehensively evaluated in this population in Taiwan. Methods A retrospective matched case-control study was conducted in the NICUs of a teaching hospital in Taiwan. The case patients were identified from a staff-maintained electronic database containing the records of BSIs from July 2003 to June 2006. The case patients and the control patients (who did not develop BSI during their NICU stay) were 1:1 matched by birth weight, gestational age, gender, Apgar score, and date of birth. Results A total of 164 infants with culture-proven BSI were identified. Of these, 74 (45.1%) infants were female. The mean gestational age and birth weight were 30.7 ± 0.7 weeks and 1512 ± 804 g, respectively. The common etiologic pathogens included coagulase-negative staphylococci (28.7%), Staphylococcus aureus (16.5%), and Klebsiella pneumoniae (14.6%). Candida spp. accounted for 11 (6.7%) episodes. Two independent factors associated with BSIs in the neonates, as identified by multivariate analysis using conditional logistic regression, were the use of parenteral nutrition (matched odds ratio [mOR], 6.07; 95% confidence interval [CI], 1.14–32.32; p = 0.034) and intraventricular hemorrhage (mOR, 2.68; 95% CI, 1.20–5.99; p = 0.017). Conclusion Parenteral nutrition was a significant and independent risk of late-onset neonatal sepsis. This risk should be considered when implementing early parenteral nutrition in NICUs.
TL;DR: Monascus-fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver and facilitate high-density lipoprotein cholesterol formation.
Abstract: Background/purposes Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear. Methods This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism. Results MS and AK lowered low-density lipoprotein cholesterol (LDL-C) and preserved high-density lipoprotein cholesterol contents. MS and AK inhibited acetyl-coenzyme A acetyltransferase, microsomal triglyceride transfer protein, and apolipoprotein (apo) B-100 expression, thereby preventing LDL assembly. In addition, enhanced LDL-receptor expression increased the transport of LDL-C to the liver for metabolism. MS and AK also significantly increase apo A1 expression, which facilitates high-density lipoprotein cholesterol formation. Conclusion Monascus-fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver.
TL;DR: The polymorphisms in the VDR and VDBP genes appeared to be responsible for host susceptibility to human TB in a Taiwanese population with TB.
Abstract: Background The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to the activation of macrophages and the deficiency of vitamin D seems to be involved in the risk of tuberculosis (TB). The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D receptor binding protein (VDBP) may be influenced by polymorphisms in the VDR and VDBP genes. In this study, variation in the VDR and VDBP genes was investigated in a Taiwanese population with TB. Methods We typed four VDR polymorphisms of restriction endonuclease sites for ApaI , TaqI , BsmI , and FokI and three VDBP polymorphisms—Thr420Lys, Asp416Glu, and Cys299Cys—in 198 patients with TB and 170 healthy volunteers. Results VDR TaqI , VDR BsmI , and VDBP Asp416Glu were significantly associated with TB susceptibility. Odd ratios of risk genotypes of the above three polymorphisms were 2.16 (95% confidence interval 1.01, 4.65), 2.14 (95% confidence interval 1.06, 4.31), and 2.24 (95% confidence interval 1.04, 4.80), respectively. VDBP haplotype analysis showed Gc1f carriers associated to TB. Conclusion The polymorphisms in the VDR and VDBP genes appeared to be responsible for host susceptibility to human TB in a Taiwanese population.
TL;DR: The TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation, and the TIC scheme has a significant benefit on improving patients' survival status.
Abstract: Background/Purpose To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline–imipenem synergy test with clinical efficacy. Methods The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group ( n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam–imipenem/cilastatin therapy, and those in the SIC group ( n = 56) received sulbactam–imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients. Results We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline–imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia ( n = 3) and Pseudomonas aeruginosa ( n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality. Conclusion Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.
TL;DR: Down's syndrome and nosocomial RSV infection are significantly associated with death in severe RSV infections, and clinicians should be alert to these conditions.
Abstract: Background Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. This retrospective study describes the clinical characteristics of severe RSV infection and determines the risk factors for death. Methods Patients were identified through a review of all patients discharged with a diagnosis of RSV lower respiratory tract infection and admitted to hospital in the pediatric intensive care unit (PICU) of a tertiary medical center between July 1, 2001 and June 30, 2010. The medical and demographic variables were recorded and analyzed. Results The 186 RSV-positive patients admitted to the PICU had a median age of 5.3 months (interquartile range 2.3–12.4 months) and included 129 boys and 57 girls. Among them, 134 had at least one underlying disease: prematurity in 92, neurological disease in 57, bronchopulmonary dysplasia in 40, congenital heart disease in 26, hematological malignancies in 11, and Down's syndrome in nine patients. The 10 patients who died from RSV-related causes had a median age of 20.8 months (interquartile range 6.6–89.2 months) and all had a comorbidity. In multivariate analysis, the risk factors for death in severe RSV infection were Down's syndrome (odds ratio 7.20, 95% confidence interval 1.13–45.76; p = 0.036) and nosocomial RSV infection (odds ratio 4.46, 95% confidence interval 1.09–18.27; p = 0.038). Conclusion Down's syndrome and nosocomial RSV infection are significantly associated with death in severe RSV infections. Clinicians should be alert to these conditions.
TL;DR: This study suggests that empowering children with knowledge and attempting to modify their water contact, and improved human waste disposal practices are necessary for schistosomiasis control.
Abstract: Background Schistosomiasis, a worldwide concern, has received attention in Swaziland through control programs such as deworming programs, education programs, and school health programs; however, these programs neglect the importance of monitoring and evaluation strategies such as assessing children's knowledge, attitudes and practices (KAPs) and the prevalence of the disease. Children are a high-risk group because of their water contact practices, and need to be informed about schistosomiasis to influence their attitudes and practices. Social and cultural factors are involved in schistosomiasis control because they instill myths and misconceptions about the disease. As a result, children in the community may be comfortable with bad practices. This study aimed to assess the KAPs of schoolchildren on schistosomiasis, and to identify practices that support or hinder the progress of schistosomiasis control. Methods In 2014, a descriptive quantitative cross-sectional survey was conducted through questionnaires among Siphofaneni primary schools, an area hit by schistosomiasis in the Lowveld of Swaziland. A logistic regression model was applied to analyze the data. Results Moderate knowledge, good attitudes, and fairly good practices were observed in the children. However, practices of certain children were risky and they still had some misconceptions. Knowledge was correlated with practice and with predictors of good and bad practices such as male sex, always urinating in water, and always using river water for domestic practices. Conclusion This study suggests that empowering children with knowledge and attempting to modify their water contact, and improved human waste disposal practices are necessary for schistosomiasis control.
TL;DR: Univariate analysis showed a higher mortality rate in patients aged >60 years and in those whose source of endocarditis was related to a prosthetic device, which is characterized by easy relapse and is highly associated with prosthetic devices.
Abstract: Background Infective endocarditis (IE) due to Pseudomonas aeruginosa is rare and accounts for only about 3% of all patients with this disease. Most infections are associated with the use of intravenous drugs. Patients with P. aeruginosa -related IE who do not use intravenous drugs are extremely rare. We carried out a review of the literature to identify the nature and risk factors of this disease. Methods Patients with IE reported between 1993 and 2013 were reviewed by searching the Medline database using the keywords "endocarditis" and " Pseudomonas aeruginosa ". All of the patients included met the definition of the modified Duke criteria. Results Twenty-seven patients in 22 reports were reviewed. IE associated with health care accounted for 20 patients (74%). The mean age of the patients was 53.4 years and there was a predominance of men (81.5%). Native valve endocarditis was seen in 20 (74.1%) patients. Surgery for infection control was performed in 15 (55.6%) patients and the mortality rate in patients who underwent surgery was 33.3% (five patients). A relapse of IE after adequate treatment was seen in nine (33.3%) patients. The mortality rate in all 27 patients was 28.6% (2/7) for those with community-acquired IE and 40% (8/20) for those with IE associated with health care. Univariate analysis showed a higher mortality rate in patients aged >60 years and in those whose source of endocarditis was related to a prosthetic device. Conclusion P. aeruginosa endocarditis has substantial morbidity and mortality. It is characterized by easy relapse and is highly associated with prosthetic devices.
TL;DR: In this paper, the combination of aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates was evaluated.
Abstract: Background/Purpose In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84–100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69–100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.
TL;DR: Salmonella endocarditis, although rare, may cause purulent infections in the perivalvular area or myocardium and lead to substantial mortality.
Abstract: Objective Salmonella endocarditis is so rarely reported that its clinical features, prognosis, and optimal treatment remain unclear. In this paper, we report a female with nontyphoid Salmonella endocarditis complicated with perivalvular abscess. We also review and summarize other cases reported in the English literature. Methods Using the key words " Salmonella ", "infective endocarditis", and "mural endocarditis" to search the PubMed database, we reviewed case reports on Salmonella endocarditis published between 1976 and 2014 and case series of infective endocarditis that included at least 500 cases. Results Salmonella species were rare infective endocarditis pathogens. Among 16 large case series, they accounted for less than 0.01% and up to 2.9% of bacterial endocarditis cases. From 1976 to 2014, a total of 87 cases of typhoid and nontyphoid Salmonella endocarditis were reported, which included 42 cases in 1976–1984, 30 cases in 1986–2002, and 15 cases in 2003–2014. Men predominated among the cases (58.6%), and the mean age was approximately 50–60 years. The major affected valves were the mitral valves (33.3%). Mural endocarditis was common (26.4%). Perivalvular abscess was only reported in 10.5% (6 cases) of 57 cases. The overall mortality rate was 42.5% and decreased over time from 69.0% to 13.3% during the three study periods. Conclusion Salmonella endocarditis, although rare, may cause purulent infections in the perivalvular area or myocardium and lead to substantial mortality.