Multi-drug-resistance MDR

Treatment for septic patients with hospital-acquired, ventilator-acquired, and health care-associated pneumonia is dependent on risk factors for multi-drug resistant (MDR) organisms (Fig. 79-2). Recommended treatment for patients with no MDR risk factors are third-generation cephalosporins, fluoroquinolones, ampicillin-sulbactam, or ertapenem (see Table 79-3).35 Recommended treatment for patients with MDR risk factors are P-lactam/p-lactamase inhibitors (piperacillin-tazobactam), antipseudomonal cephalosporin, or carbapenem, plus an aminoglycoside, plus vancomycin or linezolid (see Table 79-3).35 If an aminoglycoside is undesirable, a antipseudomonal fluoroquinolone may be utilized with a P-lactam/p-lactamase inhibitor. 

Risk Factors for Multi-drug Resistant (MDR) Pathogens... 

Augmented drug extrusion increased synthesis of the P-glycoprotein that extrudes drugs from the cell (e.g., anthracyclines, vinca alkaloids, epipodophyllotoxins, and paclitaxel) is re-ponsible for multi-drug resistance (mdr-1 gene amplification). 

The combination of structural simplicity of epothilones with respect to paclitaxel, together with their very interesting activity profile appealed different research teams, interested to overcome limitations of taxanes (poor solubility, multi drug-resistance - MDR [61-63]). Investigations on epothilones were focused on the interaction between the ligands and the paclitaxel binding site (as well as the possible similar portions between epothilones and taxanes) in order to find common pharmacopores to be used in activity improvement and design of novel molecules. 

Wilson W, Berg S, Kang K. Phase Fll study of Taxol. 96 hour infusion in refractory lymphoma and breast cancer pharmacodynamics and analysis of multi drug resistance (mdr-1). Proc Am Soc Clin Oncol 1993 335 134. 

Bacterial resistance to antibiotics continues to be a significant problem, as microorganisms appear able to develop resistance to new drugs as rapidly as they are introduced. One of the primary means by which microbes become resistant is through the development or enhancement of methods for the extrusion of antibiotics out of the cell via multi-drug resistance (MDR) pumps [98]. The function of microbial MDRs remains a hotly debated subject given the very broad substrate specificities of... 

Efflux pumps are transmembrane located transporter proteins which are expressed in various tissues including liver, placenta, the proximal tubule in the kidney, capillary endothelial cells of brain and testis, and epithelial cells of the intestine [1,2]. In addition, they are over-expressed in cancer cells and are involved in the multi drug resistance (MDR) mechanisms of tumors. Besides other mechanisms such as CYP3A, efflux pumps constitute an integral part of the body s natural detoxification system. Due to their loealisation in various tissue they affect absorption, distribution, metabolism and elimination [3]. They are... 

Larsson, R. Nygren, P. Pharmacological modification of multi-drug resistance (MDR) in vitro detected by a novel fiuorometric microculture... 

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