Resistance, to drugs

From the mechanistic point of view three basic principles of microbial resistance to drugs are known inactivation of the drug, alteration of the target, and reduced drug accumulation at the target site. However, several variations on these themes are known. 

Microbial Resistance to Drugs. Figure 1 MlC-distribution showing the number of isolates of one species with a certain MIC. Some bacterial species are naturally resistant (intrinsic resistance) to drugs because their natural MIC is above the breakpoint. Naturally sensitive isolates as well as naturally resistant ones can acquire resistance and with that increase their MIC (acquired or secondary resistance). 

Microbial Resistance to Drugs. Figure 2 Bacterial cells can obtain resistance genes in three ways ... 

Microbial Resistance to Drugs. Table 2 Antibiotic modifying enzymes [2, 3]... 

Lactam Antibiotics Microbial Resistance to Drugs Quinolones... 

Microbial Resistance to Drugs Ribosomal Protein Synthesis Inhibitors... 

Microarray Hybridization Microarray Technology Microbial Resistance to Drugs Microfrlaments Microtubule... 

One reason for the rapid growth in the use of pesticides worldwide has been the "Green Revolution" (5), Although there have been some benefits from pesticide use in agriculture, they also cause significant environmental and public health problems. The same is true in public health where Insecticides have been used to control malaria. However, today Increased resistance to insecticides in mosquitoes and Increased resistance to drugs by the malarial parasite are resulting in an explosive increase of malaria worldwide (5). 

Resistance to drug toxic effects has also been observed in children. The incidence of aminoglycoside toxicity has been reported to be much lower in infants and children than in adults [39,48]. Diminished tissue sensitivity has been suggested as an explanation. 

The human retrovirus HIV can be controlled using chemotherapy directed at the reverse transcriptase and aspartyl protease encoded by the viral genome as with other microbial pathogens, however, resistance to drug therapy becomes a major problem. Figure 7.3 shows a crystal structure (PDB 1HXW) of the HIV protease, where mutated amino acids (shown in cyan) lead to disrupted binding of the clinically effective inhibitor ritonavir [24]. 

Mycobacterium is a genus of bacteria that has characteristic cell walls and unusual staining properties. AIDS patients are most commonly infected with an atypical form of tuberculosis bacterium called Mycobacterium avium inter-cellulare. This bacterium does not normally cause disease in healthy people, but in AIDS patients, it may cause tuberculosis-like disease in the lungs. The infection can also involve numerous other tissues, such as the bone marrow, and bacteria may be present in the blood at very high levels. Patients with this opportunistic infection will have fevers and low number of white blood cells. These infections are often resistant to drugs. 

Jamieson L, Carpenter L, Biden TJ, Fields AP (1999) Protein kinase Ci activity is necessary for Bcr-Abl-mediated resistance to drug-induced apoptosis. ) Biol Chem 274 3927-3930... 

Nausea that accompanies the administration of cancer chemotherapy agents was resistant to drug intervention until the introduction of the serotonin receptor antagonist odansetron (see Chapter 13). The benzimidazolone-based compound itasetron (57-6) has much the same activity as its tricylcic predecessor. Condensation of 2-nitrophenyl-isocyanate (57-1) with the bridged bycyclic diamine (57-2) leads to the addition... 

A. The patient will continue to be resistant to drug-induced hemolysis after six months or longer. 

Given the immense value of praziquantel, the clear demonstration that schistosomes are capable of developing resistance to drugs, and the widespread applications of praziquantel... 

The main resistance to drug permeation is caused by the variant patterns of differentiation exhibited by the keratinized and nonkeratinized epithelia. As mucosal cells leave the basal layer, they differentiate and become flattened. Accumulation of lipids and proteins also occurs. This further culminates in a portion of the lipid that concentrates into small organelles called membrane-coating granules (MCGs). 

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