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Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.
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INTRODUCTION: Members of family Enterobacteriaceae are the most common Gram-negative bacteria isolated from clinical samples. Those Enterobacteriaceae which have acquired resistance to all ß-lactams antibiotics including the carbapenems are considered as Carbapenem Resistant Enterobacteriaceae (CRE). These CRE isolates are often resistant to most other classes of antimicrobials as well, making their treatment a great challenge. Tigecycline is one of the last resort antimicrobials against such multidrug resistant bacteria. Decreased tigecycline susceptibility mediated by efflux pump systems is being reported in clinical strains of Enterobacteriaceae. Minimum Inhibitory Concentration (MIC) data would prove useful in managing infections by these multidrug resistant bacteria and optimizing use of tigecycline. AIM: To evaluate the MIC values of tigecycline against carbapenem resistant Escherichia coli and Klebsiella pneumoniae isolates. MATERIALS AND METHODS: This prospective study was carried out from January 2015 to December 2015 at the Department of Microbiology, Era's Lucknow Medical College and Hospital (ELMCH), Lucknow, Uttar Pradesh, India. Antimicrobial susceptibility by disk diffusion (Kirby-bauer) was done for 491 E. coli and K. pneumoniae strains isolated from 1606 samples collected from patients admitted in various wards and ICUs. Imipenem, meropenem and ertapenem 10 µg disks were used for testing of sensitivity to carbapenems. In all isolates, Tigecycline 15 µg (Hi-Media) disk was used to screen for tigecycline resistance. In CRE isolates, MICs of tigecycline were determined by E-test (Ezy MIC TM TG strips, Hi Media) and interpreted using European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2016 guidelines. RESULTS: Out of 491 isolates tested, 186 (37.9%) were found to be CRE showing resistance to at least one of the three carbapenems tested and these included 99 E.coli and 87 K. pneumoniae. Sensitivity pattern of these two bacterial isolates shows a high level of resistance to most classes of antimicrobials. MIC testing for tigecycline was carried out in 144 CRE isolates and tigecycline resistance (MIC >2 µg/ml) was seen in 12 (8.3%) isolates (eight K.pneumoniae and four E. coli). Eight other isolates were found to have MIC of 2 µg/ml and thus the overall prevalence of isolates with decreased susceptibility was 20 (13.9%). CONCLUSION: A high prevalence of carbapenem resistance coupled with high tigecycline MICs in clinical isolates of E.coli and K. pneumoniae highlights the judicious use of a combination of antimicrobials. Routine in vitro sensitivity testing to evaluate the clinical utility of tigecycline against such resistant Enterobacteriaceae is warranted.
