Limitations of MIC as sole metric of pharmacodynamic response across the range of antimicrobial susceptibilities within a single bacterial species

Citation: Wen, X. S., Gehring, R., Stallbaumer, A., Riviere, J. E., & Volkova, V. V. (2016). Limitations of MIC as sole metric of pharmacodynamic response across the range of antimicrobial susceptibilities within a single bacterial species. Scientific Reports, 6, 8. https://doi.org/10.1038/srep37907The minimum inhibitory concentration (MIC) of an antimicrobial drug for a bacterial pathogen is used as a measure of the bacterial susceptibility to the drug. However, relationships between the antimicrobial concentration, bacterial susceptibility, and the pharmacodynamic (PD) inhibitory effect on the bacterial population are more complex. The relationships can be captured by multi-parameter models such as the E-max model. In this study, time-kill experiments were conducted with a zoonotic pathogen Pasteurella multocida and the fluoroquinolone enrofloxacin. Pasteurella multocida isolates with enrofloxacin MIC of 0.01 mu g/mL, 1.5 mu g/mL, and 2.0 mu g/mL were used. An additive inhibitory E-max model was fitted to the data on bacterial population growth inhibition at different enrofloxacin concentrations. The values of PD parameters such as maximal growth inhibition, concentration achieving a half of the maximal inhibition, and Hill coefficient that captures steepness of the relationships between the concentration and effect, varied between the isolate with low MIC and less susceptible isolates. While enrofloxacin PD against the isolate with low MIC exhibited the expected concentration-dependent characteristics, the PD against the less susceptible isolates demonstrated time-dependent characteristics. The results demonstrate that bacterial antimicrobial susceptibility may need to be described by a combination of parameters rather than a single parameter of the MIC

Near-threshold collisional dynamics in the \u3ci\u3ee\u3csup\u3e−\u3c/sup\u3ee\u3csup\u3e+\u3c/sup\u3ep\u3c/i\u3e system

We study e+-H(n) and Ps(n)-p collisions near the three-body breakup threshold and thresholds for the charge-transfer processes.We show that classical trajectoryMonte Carlo (CTMC) simulations for the three-body breakup agree reasonably well in this energy region with quantum-mechanical convergent close-coupling (CCC) calculations even if the initial hydrogen atom or positronium atom is in the ground state. The threshold behavior of the three-body breakup cross section in e+-H(1s) and Ps(1s)-p collisions agrees with the Wannier law with Klar’s exponent and obeys the classical scaling laws, although some deviation from the Klar-Wannier behavior is observed in the CCC results. Below the threshold the agreement between CTMC and CCC disappears. In particular the CTMC method fails completely for the processes of H formation in Ps(1s)-p collisions and Ps formation in e+-H collisions well below the three-body breakup threshold. For higher initial states the CTMC results below the threshold improve substantially, in accordance with the correspondence principle. This is explained by comparing the quantum-mechanical threshold laws with the classical laws

Analyzing the carbon dioxide emissions of R134a alternatives in water-cooled centrifugal chillers using the life cycle climate performance framework

Introduction: To reduce greenhouse gases, the Kigali Amendment to the Montreal Protocol seeks a phasedown of hydrofluorocarbons. R134a alternatives were analyzed for use in a water-cooled chiller: R450A, R513A, R516A, R1234ze (E), R515A, and R515B.Methods: A thermodynamic model of the chiller was employed to calculate compressor power, an input to the life cycle climate performance (LCCP) framework to estimate total equivalent carbon dioxide emissions, CO2eq. Emissions were calculated for an 809 kW [230 Tons of refrigeration (RT) nameplate] water-cooled centrifugal chiller at constant cooling capacity using five power sources (i.e., coal, distillate fuel oil, natural gas, nuclear, and wind) for a median chiller lifetime of 27 years. Two chiller operating profiles were considered: one using operational data from a university campus and a second from literature based on the Atlantic Fleet operation.Results and discussion: When powered via fossil fuels, over 90% of emissions were due to the indirect emissions from energy; therefore, the global warming potential (GWP) of the refrigerant was not the primary contributor to the total CO2eq emissions. With natural gas, total LCCP emissions were reduced for R450A (7.8%), R513A (4.7%), R516A (9.4%), R1234ze (E) (10%), R515A (8.4%), and R515B (6.4%) compared to R134a for the university campus load profile. For the round-the-clock Atlantic Fleet profile, there were emission reductions for R450A (3.6%), R513A (0.25%), R516A (2.3%), R1234ze (E) (2.4%), R515A (1.5%) and R515B (2.4%) compared to R134a. When coupled with renewable energy, the indirect emissions from the chillers substantially decreased, and GWP-dependent leakage emissions accounted for up to 74% or 40% of emissions from R134a alternatives powered by wind and nuclear, respectively. For operation using the load profile from the university campus chillers, R450A had the highest coefficient of performance (COP) of 5.802, while R513A had the lowest COP (5.606). Tradeoffs between alternative refrigerants exist in terms of operation, temperature glide, size of heat exchangers, system design, flammability, cost, availability, and material compatibility. In terms of flammability, R134a, R513A, R450A, R515B and R515A are A1 (nonflammable) fluids. R450A and R516A also have temperature glides of 0.4 K and 0.056 K, respectively, which can affect condenser design. In terms of equipment modification (sizing), R513A require fewer modifications

Some food toxic for pets

According to world statistics, dogs and cats are the species that owners most frequently seek assistance with potential poisonings, accounting 95–98% of all reported animal cases. Exposures occur more commonly in the summer and in December that is associated with the holiday season. The majority (>90%) of animal poisonings are accidental and acute in nature and occur near or at the animal owner's home. Feeding human foodstuff to pets may also prove dangerous for their health