Key factors determining the personalization of the medication of anti-infective therapy


The infectious diseases are the illness caused by the pathogenic micro-organisms such as virus, bacteria, fungi or parasites living inside our body or outside of our body. These microorganisms generally are harmless and many a times these are even helpful. However, under certain states some of these microorganism causes diseases and can spread from one person to another or from animal to human. These disease conditions are primarily treated by using the anti-infective therapy. Anti-infective agents act by inhibiting the enzymatic processes essential for the metabolic processes in microorganisms either by preventing the inflow of the important metabolite through cell all or by blocking the catabolic energy stream mechanism or by anabolic process of protein synthesis within the cell. The effectiveness and the toxicity of the anti-infective therapies often varies among patients due to the complex relationship between the host and the microbes. Therefore, it is important to consider the host and the micro-organism depended factors which would enable the clinicians effectively treat a patient. Within the human as a host for the micro-organism, anti-infective agents may have the specific pharmacokinetic and pharmacodynaic profiles. The anti-infective drug metabolism is mediated by the phase I metabolic enzymes such as CYP 450 enzymes causing the oxidative metabolism and/or the phase II metabolic enzymes such as the UDP-glucuronosyltransferases (UGT) and the glutathione-S-transferases (GST). These metabolic activity converts the drug pharmacologically active, inactive, less or more toxic metabolite. Differences in gene encoding pharmacokinetic process related protein among individuals may lead to variable expression it, causing a difference in drug exposures. Further, host mitochondrial DNA polymorphism would lead to adverse events while on treatment with anti-infective drugs (Aung et al., 2014). Linezolid, an oxazolidinone antimicrobial drug was found to be associated with the reversible lactic acidosis which and hyperlactatemia and the underlying mechanism of this adverse events is inhibition of mitochondrial protein synthesis (Carson et al., 2007). Another important host depended factor is immunologic interactions between the drug molecules, MHC peptides, and T cells. Important example of this factor is the association between abacavir hypersensitivity syndrome and the HLA class I allele HLA-B*57:0. Thus, routine use of HLA-B*57:01 screening useful to avoid abacavir related hypersensitivity reactions (Aung et al., 2014). ---------------------------------------------------------------------------------------------------------------------- Among the factors related to microorganisms, the virulence characteristics and phenotypic or genotypic resistance pattern play an important role in the individualized anti-infective therapy. Blocking the pathogenicity of virulence bacteria together with pharmacogenomic knowledge is one of the promising strategies to treat patient population. The information of resistance pattern of microorganism may further provide knowledge for the informed decision in the antimicrobial for resistance organisms. Drug resistance microorganism causes a major hindrance for individual therapy specially in hospital ICU setting. Local microbiologic data could be helpful to know the drug resistance organism and its type of resistance (Karam et al., 2016). Therefore, personalized anti-infective therapy depends not only on information related to patients or drug but also appropriate knowledge of pathogen. ---------------------------------------------------------------------------------------------------------------------- AUNG, A. K., HAAS, D. W., HULGAN, T. & PHILLIPS, E. J. 2014. Pharmacogenomics of antimicrobial agents. Pharmacogenomics, 15, 1903-1930. CARSON, J., CERDA, J., CHAE, J. H., HIRANO, M. & MAGGIORE, P. 2007. Severe lactic acidosis associated with linezolid use in a patient with the mitochondrial DNA A2706G polymorphism. Pharmacotherapy, 27, 771-4. KARAM, G., CHASTRE, J., WILCOX, M. H. & VINCENT, J.-L. 2016. Antibiotic strategies in the era of multidrug resistance. Critical Care, 20, 136.

Posted On:12/11/2019




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