Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effect on susceptibility categorisation in Germany (1997–2013)

Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. From July 1, 1997, to June 30, 2013, data on penicillin susceptibility were available for 20,437 isolates. 2,790 of these isolates (13.7 %) originate from patients with meningitis and 17,647 isolates (86.3 %) are from non-meningitis cases. A slight decline in isolates susceptible at 0.06 and 0.12 μg/ml can be noticed over the years. Overall, 89.1 % of the isolates had minimum inhibitory concentrations (MICs) of ≤0.015 μg/ml. In 2012/2013, the first three isolates of Streptococcus pneumoniae with MICs of 8 μg/ml were found. The application of different guidelines with other MIC breakpoints for the interpretation of penicillin resistance leads to differences in susceptibility categorisation. According to the pre-2008 Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, 5.3 % of isolates overall were intermediate and 1.4 % were resistant to penicillin. Application of the 2008–2014 CLSI interpretive criteria resulted in 7.6 % resistance among meningitis cases and 0.5 % intermediate resistance in non-meningitis cases. Referring to the 2009–2014 European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 7.6 % of the isolates in the meningitis group were resistant to penicillin. In the non-meningitis group, 6.1 % of the isolates were intermediate and 0.5 % were resistant. These differences should be kept in mind when surveillance studies on pneumococcal penicillin resistance are compared.     

Vaccinia‐based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection

Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell‐based vaccine, but the narrow breadth of T‐cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T‐cell immunodominance hierarchy in humans in an experimental setting, influenza‐primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN‐γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T‐cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD₅₀ challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP₃₆₆ epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV‐NP + PA showed improved protection. Taken together, a vaccinia‐based influenza vaccine expressing conserved internal proteins improved the breadth of influenza‐specific T‐cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains.     

Acidic polysaccharide of Panax ginseng regulates the mitochondria/caspase-dependent apoptotic pathway in radiation-induced damage to the jejunum in mice

Owing to its susceptibility to radiation, the small intestine of mice is valuable for studying radioprotective effects. When exposed to radiation, intestinal crypt cells immediately go through apoptosis, which impairs swift differentiation necessary for the regeneration of intestinal villi. Our previous studies have elucidated that acidic polysaccharide of Panax ginseng (APG) protects the mouse small intestine from radiation-induced damage by lengthening villi with proliferation and repopulation of crypt cells. In the present study, we identified the molecular mechanism involved. C57BL/6 mice were irradiated with gamma-rays with or without APG and the expression levels of apoptosis-related molecules in the jejunum were investigated using immunohistochemistry. APG pretreatment strongly decreased the radiation-induced apoptosis in the jejunum. It increased the expression levels of anti-apoptotic proteins (Bcl-2 and Bcl-X_S/L) and dramatically reduced the expression levels of pro-apoptotic proteins (p53, BAX, cytochrome c and caspase-3). Therefore, APG attenuated the apoptosis through the intrinsic pathway, which is controlled by p53 and Bcl-2 family members. Results presented in this study suggest that APG protects the mouse small intestine from irradiation-induced apoptosis through inhibition of the p53-dependent pathway and the mitochondria/caspase pathway. Thus, APG may be a potential agent for preventing radiation induced injuries in intestinal cells during radio-therapy such as in cancer treatment.     

A comparison between central blood pressure values obtained by the Gaon system and the SphygmoCor system

Central pulse pressure is correlated with carotid atherosclerosis and the incidence of cardiovascular events more significantly than brachial pulse pressure. Augmentation index (Aix) has been shown to be an independent predictor of cardiovascular morbidity and mortality. Pulse wave analysis using the Gaon system allows for the estimation of central blood pressure (CBP), corrected augmentation index (Aix@HR75), ejection duration (ED) and subendocardial viability ratio (SEVR), and is widely used in clinical research in Korea. However, the accuracy of this system is controversial. From February 2008 to March 2011, 99 patients were recruited for this study. Measurements were taken both by the Gaon system and the SphygmoCor system on the same day for all study participants. The estimated values of CBP, Aix@HR75, ED and SEVR for the two systems were compared using paired t-tests, simple correlation analyses and Bland-Altman plots. Systolic blood pressure (SBP) estimated by the two systems was significantly (P<0.001) correlated; the coefficient was 0.982. The two s.d. of the difference in SBP between these systems was quite small--<7?mm?Hg. Aix@HR75, ED and SEVR as estimated by the two systems were also significantly correlated, although they, especially SEVR, showed much weaker correlations than were observed in SBP: coefficients for Aix@HR75, ED and SEVR were 0.727, 0.648 and 0.230, respectively. We assessed the CBP of Korean patients estimated by the two systems and observed that the correlations of Aix, ED and SEVR were weaker than that of CBP. Such variations may be due to the difference in measuring methods between the devices. As even a slight change in pulse waveforms may result in a large difference in estimations, parameters, including Aix@HR75, ED and SEVR, should be carefully interpreted by experienced clinicians.