scholarly journals Real-Time Optimization of Pharmacodynamic Target Attainment at Infection Site during Treatment of Post-Neurosurgical Ventriculitis Caused by Carbapenem-Resistant Gram Negatives with Ceftazidime–Avibactam-Based Regimens: A Report of Two Cases

2022 ◽  
Vol 10 (1) ◽  
pp. 154
Author(s):  
Milo Gatti ◽  
Giulio Virgili ◽  
Pier Giorgio Cojutti ◽  
Paolo Gaibani ◽  
Matteo Conti ◽  
...  
Keyword(s):  
Real Time ◽  
High Dose ◽  
Infection Site ◽  
Target Attainment ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Time Optimization ◽  
Real Time Optimization ◽  
Over Time

We present two cases of post-neurosurgical ventriculitis caused by carbapenem-resistant Gram-negative pathogens successfully treated with high-dose ceftazidime/avibactam. The existence of a real-time clinical pharmacological advice program, by enabling the optimization of the PK/PD targets over time at the infection site, turned out to be very helpful.

scholarly journals Cefepime/sulbactam as an enhanced antimicrobial combination therapy for the treatment of MDR Gram-negative infections

2019 ◽  
Author(s):  
David W Wareham ◽  
M H F Abdul Momin ◽  
Lynette M Phee ◽  
Michael Hornsey ◽  
Joseph F Standing
Keyword(s):  
Fixed Ratio ◽  
Vitro Activity ◽  
Definitive Treatment ◽  
High Dose ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Pharmacodynamic Modelling ◽  
Carbapenem Resistant ◽  
Combination Regimens

Abstract Background β-Lactam (BL)/β-lactamase inhibitor (BLI) combinations are widely used for the treatment of Gram-negative infections. Cefepime has not been widely studied in combination with BLIs. Sulbactam, with dual BL/BLI activity, has been partnered with very few BLs. We investigated the potential of cefepime/sulbactam as an unorthodox BL/BLI combination against MDR Gram-negative bacteria. Methods In vitro activity of cefepime/sulbactam (1:1, 1:2 and 2:1) was assessed against 157 strains. Monte Carlo simulation was used to predict the PTA with a number of simulated cefepime combination regimens, modelled across putative cefepime/sulbactam breakpoints (≤16/≤0.25 mg/L). Results Cefepime/sulbactam was more active (MIC50/MIC90 8/8–64/128 mg/L) compared with either drug alone (MIC50/MIC90 128 to >256 mg/L). Activity was enhanced when sulbactam was added at 1:1 or 1:2 (P < 0.05). Reduction in MIC was most notable against Acinetobacter baumannii and Enterobacterales (MIC 8/8–32/64 mg/L). Pharmacokinetic/pharmacodynamic modelling highlighted that up to 48% of all isolates and 73% of carbapenem-resistant A. baumannii with a cefepime/sulbactam MIC of ≤16/≤8 mg/L may be treatable with a high-dose, fixed-ratio (1:1 or 1:2) combination of cefepime/sulbactam. Conclusions Cefepime/sulbactam (1:1 or 1:2) displays enhanced in vitro activity versus MDR Gram-negative pathogens. It could be a potential alternative to existing BL/BLI combinations for isolates with a cefepime/sulbactam MIC of 16/8 mg/L either as a definitive treatment or as a carbapenem-sparing option.

scholarly journals Experimental real-time optimization of a solid oxide fuel cell stack via constraint adaptation

Energy ◽  
2012 ◽  
Vol 39 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Gene A. Bunin ◽  
Zacharie Wuillemin ◽  
Grégory François ◽  
Arata Nakajo ◽  
Leonidas Tsikonis ◽  
...  
Keyword(s):  
Fuel Cell ◽  
Solid Oxide Fuel Cell ◽  
Real Time ◽  
Solid Oxide ◽  
Oxide Fuel ◽  
Fuel Cell Stack ◽  
Time Optimization ◽  
Real Time Optimization

Real-Time Optimization of Wind Farm Energy Capture With Delay Compensated Nested-Loop Extremum Seeking Control

2017 ◽  
Author(s):  
Zhongyou Wu ◽  
Yaoyu Li
Keyword(s):  
Wind Turbine ◽  
Real Time ◽  
Wind Farm ◽  
Optimization Techniques ◽  
Extremum Seeking ◽  
Extremum Seeking Control ◽  
Energy Capture ◽  
Time Optimization ◽  
Real Time Optimization ◽  
Nested Loop

Real-time optimization of wind farm energy capture for below rated wind speed is critical for reducing the levelized cost of energy (LCOE). Performance of model based control and optimization techniques can be significantly limited by the difficulty in obtaining accurate turbine and farm models in field operation, as well as the prohibitive cost for accurate wind measurements. The Nested-Loop Extremum Seeking Control (NLESC), recently proposed as a model free method has demonstrated its great potential in wind farm energy capture optimization. However, a major limitation of previous work is the slow convergence, for which a primary cause is the low dither frequencies used by upwind turbines, primarily due to wake propagation delay through the turbine array. In this study, NLESC is enhanced with the predictor based delay compensation proposed by Oliveira and Krstic [1], which allows the use of higher dither frequencies for upwind turbines. The convergence speed can thus be improved, increasing the energy capture consequently. Simulation study is performed for a cascaded three-turbine array using the SimWindFarm platform. Simulation results show the improved energy capture of the wind turbine array under smooth and turbulent wind conditions, even up to 10% turbulence intensity. The impact of the proposed optimization methods on the fatigue loads of wind turbine structures is also evaluated.

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