Chien-Ying Liu

Clinical features, antimicrobial susceptibilities, and outcomes of Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) bacteremia at a medical center in Taiwan, 1999-2006.

A total of 118 patients with Elizabethkingia meningoseptica bacteremia at a medical center in Taiwan from 1999 to 2006 were studied. Minimum inhibitory concentrations (MICs) of 99 preserved isolates were determined. The incidence (per 100,000 admissions) of E. meningoseptica bacteremia increased from 7.5 in 1996 to 35.6 in 2006 (pu2009=u20090.006). Among them, 84% presented with fever, 86% had nosocomial infections, and 60% had acquired the infection in intensive care units (ICUs). The most common underlying diseases were malignancy (36%) and diabetes mellitus (25%). Seventy-eight percent of patients had primary bacteremia, followed by pneumonia (9%), soft tissue infection, and catheter-related bacteremia (6%). Forty-five patients (38%) had polymicrobial bacteremia. Overall, the 14-day mortality was 23.4%. Multivariate analysis revealed E. meningoseptica bacteremia acquired in an ICU (pu2009=u20090.048, odds ratio [OR] 4.23) and presence of effective antibiotic treatment after the availability of culture results (pu2009=u20090.049, OR 0.31) were independent predictors of 14-day mortality. The 14-day mortality was higher among patients receiving carbapenems (pu2009=u20090.046) than fluoroquinolones or other antimicrobial agents. More than 80% of the isolates tested were susceptible to trimethoprim-sulfamethoxzole, moxifloxacin, and levofloxacin. The MIC50 and MIC90 of the isolates to tigecycline and doxycycline were both 4xa0μg/mL and 8xa0μg/ml, respectively.

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006–2010

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7xa0% were susceptible; however, 30.0xa0% (nu2009=u2009517) exhibited MICs of 2 μg/ml and 0.3xa0% (nu2009=u20096) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥99.9xa0%) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC90 values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (nu2009=u20096), teicoplanin (nu2009=u20091), daptomycin (nu2009=u20092), or tigecycline (nu2009=u20091), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

Cytoprotective response of A1, a Bcl-2 homologue expressed in mature human neutrophils and promyelocytic HL-60 cells, to oxidant stress-induced cell death.

The ability to generate reactive oxidative intermediates is one of the quintessential properties of mature human neutrophils. Endogenously generated oxidants have been shown to be an important mechanism underlying neutrophil cell death. In acute lung inflammation, newly recruited neutrophils further encounter external oxidants, including reactive oxygen and nitrogen intermediates. In our present study, we showed that A1, a constitutive and inducible Bcl-2 homologue expressed in mature circulating human neutrophils, might confer the protection from hydrogen peroxide (H(2)O(2))- and peroxynitrite (ONOO)-induced cell death. Utilizing the myeloid precursor cell line, HL-60, we further examined the hypothesis that A1 was capable of conferring cytoprotective activity against these oxidative stresses. Whereas the control-transfected HL-60 cells expressed small amounts of A1 and were sensitive to the biologically relevant, cell death-inducing oxidants, H(2)O(2) and ONOO, the stable transfectants that overexpressed A1 were significantly more tolerant. Furthermore, there was a correlation between the level of A1 expression and the antiapoptotic activity. Thus, our results suggest a cytoprotective role of A1 in mature human neutrophils under oxidant stresses in host defense and inflammation.

Bacteremia caused by Acinetobacter junii at a medical center in Taiwan, 2000–2010

We investigated the clinical characteristics and outcomes of 43 patients with Acinetobacter junii bacteremia at a 2,500-bed tertiary care center in northern Taiwan. These organisms were confirmed to the species level by an array assay and 16S rRNA gene sequence analysis. The antimicrobial susceptibilities of the 43 A. junii isolates to 13 agents were determined using the agar dilution method. Susceptibility testing for tigecycline was determined using the broth microdilution method. Most of the patients were hospital-acquired (nu2009=u200936, 83.7xa0%) or healthcare facility-related infections (nu2009=u20096, 13.9xa0%), and 55.8xa0% had impaired immunity. Central venous access devices were present in 35 (81.4xa0%) patients; among the total of 43 patients with A. junii bacteremia, 8 patients were diagnosed as catheter-related bloodstream infection and 19 patients were diagnosed as catheter-associated bloodstream infection. Shock requiring inotropic agents occurred in 2 patients (4.6xa0%). Most patients developed bacteremia in general wards (nu2009=u200936, 83.7xa0%). The overall in-hospital mortality rate was low (7xa0%), despite the low rate of removal of central venous devices, low rate of holding usage of original central venous devices, and high rate of inappropriate antimicrobial regimens. Carbapenems, fluoroquinolones, and amikacin had potent activity (>95xa0% susceptible rate) against A. junii isolates. Interestingly, 35xa0% of the A. junii isolates were resistant to colistin. Tigecycline exhibited low minimum inhibitory concentration (MIC) values (range, 0.06–2 μg/ml, MIC90, 1 μg/ml) against the A. junii isolates.

Impact of prolonged and early bevacizumab treatment on the overall survival of EGFR-mutant and EGFR-wild type nonsquamous non-small cell lung cancer: Bevacizumab treatment strategies

VEGF plays a key role in tumor angiogenesis and immunosuppression. VEGF‐blocking has proven beneficial for EGFR mutant and wild‐type nonsquamous non‐small cell lung cancer (nonsq‐NSCLC); however, the number of cycles and treatment line yielding the optimal benefit are unknown.

Corrigendum: SUV39H1 Reduction Is Implicated in Abnormal Inflammation in COPD

This corrects the article DOI: 10.1038/srep46667.

Erythromycin Modulates β2-integrins (CD11b/CD18) Expression and Intracellular Oxidant Capacity in Airway Neutrophils of Patients with Bronchiectasis

Bronchiectasis is a chronic airway disease of diverse etiology, characterised by persistent becterial colonization, bronchial inflammation, and progressive tissue damage. A neutrophil influx with oxidants and pro-inflammatory cytokines production not only provides opsonophagocytic protection from microbes, but is also implicated in further airway inflammation. To investigate whether erythromycin (EM) can affect neutrophil-mediated antimicrobes and airway inflammation, a 2-week course of therapy with EM (250 mg, 4 times per day) or duracef (250 mg, twice per day) was administered. Twenty-three bronchiectasis patients in stable condition after adequate chest care and hydration were enrolled in a randomized fashion. Leukocyte adhesion molecules CD11b/CD18 and DCFH in induced sputum and blood samples were determined by flow cytometric assay, and the sputum IL-8 and TNF-α levels were measured using the ELISA method before and after treatment. EM significantly increased the expression of CD11b and CD18, from 296.6±31.0 [expressed as mean fluorescence intensity (M.F.I.) of 10000 cells] to 416.1±35.1, and from 265.3±23.0 to 350.4±21.1 (p＜0.05; respectively), but not in patients using duracef (308.2±19.8 to 325.9±19.8 and 280.2±19.3 to 277.6±14.9). There were significant correlations between the expressions of baseline CD11b and CD18 before antibiotic therapy (r=0.72, n=23, p＜0.0001) and between the changes in CD11b and CD18 either after treatment with erythromycin (r=0.77, n=13, p＜0.005) or in both groups (r=0.72, n=23, p=0.0001). The mean DCF fluorescence intensity of neutrophils in the induced sputum of patients receiving EM was significantly increased, from 400.8±49.1 to 811.3±129.2 (p＜0.01), whereas duracef did not change the mean DCF fluorescence intensity (from 495.6±141.0 to 531.2±129.9; p＞0.05). The TNF-α and IL-8 levels in the EM and duracef groups did not significantly change after treatment. In conclusion, EM upregulates the expression of CD11b/CD18 on neutrophils to increase the production of intracellular H2O2, for a microcidal effect.