Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Alpinia oxyphylla Fruit Extract Ameliorates Experimental Autoimmune Encephalomyelitis through the Regulation of Th1/Th17 Cells.

Alpinia oxyphylla is a traditional Chinese medicine widely used for treating diarrhea, ulceration, and enuresis. Moreover, A. oxyphylla is effective for cognitive function improvement and nerve regeneration. Multiple sclerosis (MS) is a chronic neuronal inflammatory autoimmune disease that commonly affects young adults in high-latitude regions. The aim of this study was to evaluate the beneficial effects of A. oxyphylla in an experimental autoimmune encephalomyelitis (EAE) mouse model, which is an extensively used model for human MS. The ethanolic extract of A. oxyphylla fruit (AO-1) was orally administered to EAE mice. Our results showed AO-1 significantly reduced EAE symptoms. Histopathological analysis showed AO-1 reduced demyelination, inflammation, gliosis, and axonal swelling in the spinal cord. Furthermore, immunohistochemistry and quantitative polymerase chain reaction (qPCR) studies revealed that the infiltration of CD4+, CD8+ T cells, and CD11b+ monocytes into the spinal cord decreased in the AO-1-treated group. Mechanistically, the Th1 transcription factor T-bet, Th17 transcription factor retinoic acid receptor-related orphan receptor γ (RORγt), and inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17 were reduced in the spinal cords of mice treated with AO-1. The expression levels of T-bet and RORγt were also lowered in the spleens of those mice. Further in vitro study showed AO-1 inhibited production of IFN-γ, IL-2, and tumor necrosis factor-α from MOG35-55-peptide-stimulated splenocytes. One component isolated from AO-1, yakuchinone A, inhibited IL-17 production in vitro and reduced EAE symptoms in the mice. Collectively, our results indicate that AO-1 ameliorated the severity of EAE in mice and may involve the regulation of Th1/Th17 response. A. oxyphylla warrants further investigation, particularly regarding its clinical benefits for MS.

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

OBJECTIVES: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. DESIGN: Prospective, observational, multicenter study. SETTING, PATIENTS, AND INTERVENTIONS: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009). CONCLUSIONS: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

Human 8-oxoguanine DNA glycosylase 1 mRNA expression as an oxidative stress exposure biomarker of cooking oil fumes.

Epidemiological studies have indicated that the exposure to carcinogenic components formed during the cooking of food might be associated with lung cancer risk of Chinese women. Previous studies have confirmed that cooking oil fumes from frying fish (COF) contained relatively high amount of benzo[a]pyrene, 2-methyl-3,8-dimethylimidazo[4,5-f] qunoxaline, benzene, and 1,3-butadiene, reported in fumes from heated soybean oil. Thus, we consider that oxidative stress induced by COF may play a role in lung cancer development among Chinese women. To verify whether the oxidative DNA damage was induced by COF, high-performance liquid chromatography (HPLC) analysis data showed that the levels of 8-hydroxydeoxyguanine (8-OH dG) were increased in a dose-dependent manner when calf thymus DNA reacted with various concentrations of COF. Since human 8-oxoguanine DNA glycosylase 1 (hOGG1) was a repair enzyme for removing 8- OH dG from damaged DNA, we hypothesized that hOGG1 mRNA may be used to assess the risk of oxidative damage induced by the exposure of COF. The results from reverse-transcription polymerase chain reaction showed that the hOGG1 mRNA expression was induced by hydrogen peroxide (H2O2) and COF in human lung adenocarcinoma CL-3 cells. To elucidate whether hOGG1 mRNA expression was an exposure biomarker of COF, a cross-sectional study of 238 subjects including 94 professional cooks, 43 housewives, and 101 COF-nonexposed control subjects was conducted. The hOGG1 mRNA expression frequencies of COF-exposed cooks (27 of 94, 28.7%) and housewives (6 of 43, 14%) were significantly higher than those of control subjects (4 of 101, 4%). After adjusting for age, sex, and smoking and drinking status, the odds risks (ORs) of housewives versus control and cooks versus control were 3.94 (95% confidence interval [CI] = 0.95-16.62) and 10.12 (95% CI = 2.83-36.15), respectively. These results indicated that hOGG1 may be adequate to act as an exposure biomarker to assess the oxidative DNA damage induced by COF. This also suggests that oxidative stress induced by COF may play a role in lung cancer development among Chinese women.