Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

AbstractBackground/PurposeFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.ResultsA total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p < 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; p = 0.05).ConslusionFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be considered as a carbapenem-sparing alternative

TRPC5 channels participate in pressure-sensing in aortic baroreceptors

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A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P \u3c 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P \u3c 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials

Age and Geochemical Features of Dredged Basalts from Offshore SW Taiwan: The Coincidence of Intra-Plate Magmatism with the Spreading South China Sea

This study reports age and geochemical analyses of basaltic rocks dredged from volcanic seamounts offshore SW Taiwan. 40Ar/39Ar dating results of these rocks show them to be of the early Miocene age of ~22 - 21 Ma. They are evolved alkali basalts that show OIB-type geochemical features similar to post-spreading seamount basalts (14 - 3.5 Ma) in the South China Sea (SCS) and Miocene intraplate basalts on the Penghu Islands (16 - 8 Ma) and NW Taiwan (23 - 9 Ma). Their Sr-Nd-Pb isotope data plot within the range of the SCS seamount basalts that show an EM2-like component in the mantle source. The age and overall geochemical characteristics of the dredged basalts are comparable to those of the Kungkuan basalts, NW Taiwan and Baolai basalts, SW Taiwan, suggesting an extensive alkali basaltic volcanism along the southeastern Eurasian continental margin during the early Miocene that resulted from regional lithospheric extension in association with seafloor spreading in the South China Sea