ABSTRACT
Background: The emergence of antimicrobial resistance is a worldwide challenge threatening to negate the gains made by discovery of antimicrobial agents (AMAs). Antimicrobial Stewardship Program (ASP) is an important strategy for ensuring appropriate use of AMAs and controlling emergence of antibiotic resistance. Implementation of ASP must start with assessment of the current state of antimicrobial use. This study was therefore conducted to assess the prevalent prescribing patterns in a tertiary care hospital and identify gaps which warrant corrective intervention.Methods: This prospective pilot study presents analysis of the first 30 Patients from the medicine ward prescribed at least one antimicrobial agent during the two months of study period. Relevant data was collected in AMA record form. Appropriateness of AMAs was analyzed regarding selection as well as administration protocol as per the hospital antibiotic policy.Results: Out of the 60 AMAs prescribed to these patients, most commonly prescribed were cephalosporins (63.3%), anti-amoebics (26.6%) and macrolides (23.3%). Common diseases involved were urinary tract infection, acute gastroenteritis, sepsis and lower respiratory tract infections. Use of AMAs was found to be appropriate for the indication in 42 %, dose in 97%, duration 60 %, route 93% and frequency 90 %.Conclusions: This gap between the appropriate and the actual practice use of AMAs indicates an urgent need of rigorous implementation of ASP in order to avoid emergence of resistance and to conserve the sensitivity to the available AMAs.
ABSTRACT
Background: Tacrolimus (Tac) a calcineurin inhibitor (CNI), is a potent immunosuppressive drug which is widely used in organ transplant recipients. The drug has a narrow therapeutic window and high inter-individual pharmacokinetic variability. Tac is metabolized by cytochrome P450 3A (CYP3A) enzymes. The CYP3A5 activity is largely determined by the single nucleotide variant (SNV) CYP3A5*3 (c.219-237A>G; rs776746), which results in alternate mRNA splicing and a non-functional protein.Methods: An observational prospective study was carried out at nephrology centre of army hospital where the consenting patients were enrolled in the study. The whole blood sample drawn was utilized to analyze for plasma drug concentration of Tac and genotyping for the CYP3A*5 polymorphism by the method as described by Cheung et al.Results: 100 patients participated with an average of 98±8 days after transplantation. Recipients having heterozygous CYP3A5*1 genotype manifested 70% lower mean steady state concentration of Tac (C0/D ratio) 1.67±0.43 ?g*l-1/mg in comparison to homozygote carriers of CYP3A5*3 5.60±1.94 ?g*l-1/mg p<0.001.Conclusions: Study suggested that Indian sub population closely mimics Caucasian population in terms of genotype expression for CYP3A5*3, who are expressing a non-functional enzyme for metabolism. Also, this study reinforces that population genotype CYP3A5*1 is significantly associated with lower C0/D ratio for Tac than the ones expressing homozygous CYP3A5*3 genotype. It also established the importance of pre-transplant genotyping, for better individualization of Tac doses. Further studies are suggested for population pharmacokinetic modelling study in future to derive starting dosage of Tac based on profiling of CYP3 genetics in recipients.
ABSTRACT
Objective: The objective of the following study is to detect genes encoding carbapenem resistance in Klebsiella pneumoniae sepsis outbreak in a neonatal intensive care unit (NICU). Materials and Methods: Antibiotic sensitivity test was performed by standard Kirby Bauer disc diffusion technique and minimum inhibitory concentrations of antibiotics was determined by VITEK-2. Polymerase chain reaction (PCR) assays and sequencing was used to determine the presence of beta-lactamase encoding genes. Conjugation experiments were performed to determine the transferability of beta-lactamase. Isolate relatedness were determined by repetitive-element PCR (REP), enterobacterial repetitive intergenic consensus (ERIC) PCR and random amplifi ed polymorphic deoxyribonucleic acid (RAPD). Results: All the isolates were completely resistant to the second and third generation cephalosporins tested as well as carbapenems. Susceptibility profi ling of the isolates indicated that 100% retained susceptibility to tigecycline and colistin. Conjugation experiments indicated that blaNDM-1 was transferable and likely through a plasmid-mediated event. All the isolates showed the presence of blaNDM-1 with co association of blaCTX-M-15. REP-PCR, ERIC-PCR and RAPD revealed a single clonal type circulating in NICU environment. Conclusion: Co-production of NDM-1 with CTX-M-15 in K. pneumoniae isolates was detected for the fi rst time in our NICU. Transmission of plasmid carrying these resistant genes to other members of Enterobacteriaceae will increase the incidence of multidrug resistance. Early detection of these genes will help in prevention and adequate infection control by limiting the spread of these organisms.