Study of resistance pattern of isolated micro-organisms towards commonly used anti-microbial agents in medical intensive care unit of a tertiary care teaching hospital

Background: The objective of the study was to find out different types of biological samples from admitted patients tested for culture and sensitivity (C&S), prevalence of different types of organisms isolated from those samples, and to analyze the resistance pattern of those isolated organisms against commonly used or tested anti-microbial agents (AMAs).Methods: Following institutional ethics committee approval and written informed consent, adult patients of both genders, receiving AMAs were enrolled from June 2014 to July 2015 and followed up daily till they were in medical intensive care unit (MICU). Demographic data, diagnosis, culture-sensitivity (antibiogram) and other investigation reports and treatment details were recorded. Descriptive statistical analysis of collected data was done.Results: Of the 514 samples (from 600 patients enrolled) sent for C&S testing, 143 were reported as sterile while from the rest 371 samples, 504 organisms were isolated; commonly isolated organisms were Pseudomonas aeruginosa (30%), Acinetobacter baumannii (23%), Klebsiella pneumoniae (16%), Providencia sp. (7.1%), Escherichia coli (5.7%), and Enterobacter sp. (4.2%). Samples were sent in 63% of enrolled patients, the commonest being broncho-alveolar lavage (48% of total). Microbial resistance was high for cephalosporins (ceftriaxone, cefepime, ceftazidime), carbapenems (meropenem, imipenem), penicillins (piperacillin), quinolones (ciprofloxacin, levofloxacin), aminoglycosides (gentamicin, netilmicin, amikacin) and cotrimoxazole. Most organisms were sensitive to colistin (100%), polymyxin B (92%) and tigecycline (69%).Conclusions: The information regarding commonly isolated organisms and their resistant pattern would aid in rational selection of AMAs and thus the present study is useful to clinicians managing MICU and the hospital infection committee to plan future policies regarding AMA use in MICU

Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit

Objective: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. Methods: This was an audit of data collected between July 2011 and December 2016. For safety and efficacy, patients were divided into two subgroups: those with or without bleeding and those who achieved target INR or not. Chi square test was applied to compare the between group differences and crude Odds Ratio (cOR) calculated. Results: Among 521 patients evaluated, most common indication for warfarin therapy was valvular heart disease (210/521 = 40%); 36% (187/521) had at least one bleeding episode; 56% (269/479) had below target INR. 26% (136/521) had polymorphic alleles of CYP2C9 and 69% (358/521) had the GG haplotype of VKORC1. Polymorphic alleles of CYP2C9 or AG/AA haplotype had twice the odds of bleeding (cOR = 2.14 and 2.44 respectively) relative to those with wild CYP2C9 allele or GG haplotype. Combined CYP2C9 mutant alleles and/or AG/AA haplotypes had thrice the odds of bleeding (cOR = 3.12) relative to those with wild CYP2C9 alleles and GG haplotype. Those with GG haplotype had twice the odds (cOR = 1.81) and those with GG haplotype along with wild CYP2C9 allele had four times the odds (cOR = 4.27) of not achieving the target INR relative to those with other haplotype/alleles. All these associations were statistically significant (p < 0.05). Conclusions: Pretesting patients for genetic polymorphisms could aid in individualizing warfarin therapy. Keywords: Genotype, Haplotype, Personalized medicine, Mutation, Bleeding, International Normalized Ratio (INR