Factors influencing the potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida

For the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, Minimum Inhibitory Concentration (MIC) of marbofloxacin was determined in recommended broths and pig serum at three inoculum strengths. MICs in both growth matrices increased progressively from low, through medium to high starting inoculum counts, 104, 106 and 108 CFU/mL, respectively. P. multocida MIC ratios for high:low inocula were 14:4:1 for broth and 28.2:1 for serum. Corresponding MIC ratios for A. pleuropneumoniae were lower, 4.1:1 (broth) and 9.2:1 (serum). MIC high:low ratios were therefore both growth matrix and bacterial species dependent. The effect of alterations to the chemical composition of broths and serum on MIC were also investigated. Neither adjusting broth or serum pH in six increments over the range 7.0 to 8.0 nor increasing calcium and magnesium concentrations of broth in seven incremental steps significantly affected MICs for either organism. In time-kill studies, the killing action of marbofloxacin had the characteristics of concentration dependency against both organisms in both growth matrices. It is concluded that MIC and time-kill data for marbofloxacin, generated in serum, might be preferable to broth data, for predicting dosages of marbofloxacin for clinical use

Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media

Pharmacodynamic properties of marbofloxacin were established for six isolates each of the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Three in vitro indices of potency were determined; Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Mutant Prevention Concentration (MPC). For MIC determination Clinical Laboratory Standards Institute guidelines were modified in three respects: (1) comparison was made between two growth media, an artificial broth and pig serum; (2) a high inoculum count was used to simulate heavy clinical bacteriological loads; and (3) five overlapping sets of two-fold dilutions were used to improve accuracy of determinations. Similar methods were used for MBC and MPC estimations. MIC and MPC serum:broth ratios for A. pleuropneumoniae were 0.79:1 and 0.99:1, respectively, and corresponding values for P. multocida were 1.12:1 and 1.32:1. Serum protein binding of marbofloxacin was 49%, so that fraction unbound (fu) serum MIC values were significantly lower than those predicted by correction for protein binding; fu serum:broth MIC ratios were 0.40:1 (A. pleuropneumoniae) and 0.50:1 (P. multocida). For broth, MPC:MIC ratios were 13.7:1 (A. pleuropneumoniae) and 14.2:1 (P. multocida). Corresponding ratios for serum were similar, 17.2:1 and 18.8:1, respectively. It is suggested that, for dose prediction purposes, serum data might be preferable to potency indices measured in broths

Does hemispheric lateralization influence functional and cardiovascular outcomes after stroke?: an analysis of placebo-treated patients from prospective acute stroke trials

<p><b>Background and Purpose:</b> The influence of stroke lateralization on functional and cardiovascular outcome after stroke is not well established. We evaluated the influence of hemispheric lateralization among patients enrolled in prospective acute stroke trials.</p> <p><b>Methods:</b> We obtained data from the VISTA database for acute stroke trials which reported lateralization. Baseline data, cardiac adverse events, and 90-day outcomes were compared between right and left hemisphere stroke patients. A "hemisphere unbiased" subscore of the NIHSS which omitted items strongly associated with lateralized cognitive deficits was also compared for trials which reported individual NIHSS item scores. A multivariable analysis of outcome predictors was performed.</p> <p><b>Results:</b> Three acute stroke trials met the prespecified inclusion criteria. 1644 placebo-treated patients with documented hemispheric lateralization were included in the analysis. Baseline NIHSS was higher for left hemisphere patients (mean 16.2, versus 12.8 right, P < 0.001); there was no difference in the "hemisphere unbiased" NIHSS subscore (10.88 left, 11.08 right, n=687, P= 0.49). There was no difference between hemispheres in 90-day modified Rankin Score (3.43 left, 3.29 right, P=0.13), mortality (22.1% left, 19.5% right, P=0.20), or cardiac adverse events (P=0.71). Hemispheric lateralization was not an independent predictor of outcome in the multivariable analysis after controlling for the hemispheric bias intrinsic to the NIHSS.</p> <p><b>Conclusions:</b> There is no difference in functional outcome between patients with right or left hemisphere stroke. Use of the baseline NIHSS score to predict stroke outcome must take hemispheric lateralization into account. Stroke lateralization is not an important predictor of cardiac adverse events or 90-day mortality.</p&gt