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Kazi M.,Pd Hinduja Hospital & Medical Research Center | Drego L.,Pd Hinduja Hospital & Medical Research Center | Nikam C.,Pd Hinduja Hospital & Medical Research Center | Ajbani K.,Pd Hinduja Hospital & Medical Research Center | And 3 more authors.
European Journal of Clinical Microbiology and Infectious Diseases

Carbapenem-hydrolyzing β-lactamases are increasingly reported worldwide, leading to therapeutic failure. In an era where the drug development pipeline is stagnant, it is crucial to preserve current classes of antibiotics to help fight against infection caused by multidrug-resistant organisms (MDROs), by practicing a rational approach for the use of antibiotics. Identifying the mechanisms of resistance gives us much needed insights in this field. A total of 113 consecutive, non-duplicate carbapenem-resistant clinical isolates were collected from July to December 2012. These isolates were subjected to the modified Hodge test (MHT) for phenotypic detection of carbapenemases, an inhibitor-based test employing EDTA for the detection of metallo-β-lactamase (MBL), and phenylboronic acid for the detection of Klebsiella pneumoniae carbapenemase (KPC). A multiplex polymerase chain reaction (PCR) assay that characterized the five most predominant carbapenemases (blaNDM, blaOXA, blaVIM, blaIMP, blaKPC) was designed. The 113 isolates consisted of Klebsiella spp. (46), Enterobacter spp. (32), Escherichia coli (31), Citrobacter spp. (2), Proteus spp. (1), and Morganella spp. (1). blaNDM-1 was the most prevalent carbapenemase and accounted for 75.22 % (85/113) of the isolates. This was followed by blaOXA [4.42 % (n = 5)]. 18.5 % (21/113) of the isolates possessed dual carbapenemase genes. 98.9 % concordance was observed between the phenotypic tests and the molecular tests for the detection of MBL. In conclusion, patients infected with resistant bacteria require early appropriate antimicrobial treatment for good clinical outcome. Thus, identifying the resistant mechanisms of suspected pathogens becomes crucial. Also, the high incidence of plasmid-mediated blaNDM-1 calls for the implementation of strict infection control and contact isolation precautions in order to prevent the spread of these organisms. © 2014, Springer-Verlag Berlin Heidelberg. Source

Chawla P.K.,Research Laboratories | Nanday S.R.,Pd Hinduja Hospital & Medical Research Center | Dherai A.J.,Research Laboratories | Dherai A.J.,Pd Hinduja Hospital & Medical Research Center | And 5 more authors.
International Journal of Clinical Pharmacy

Background Voriconazole is an antifungal drug essentially metabolized by cytochrome P450 (CYP2C19) isozyme. Plasma voriconazole levels exhibit wide inter-individual variability due to several factors like age, weight, food or drug interactions or CYP2C19 polymorphisms. Objective In the present study, we assessed the correlation of voriconazole levels with CYP2C19 genotype in patients on voriconazole therapy. Setting Biochemistry Department of a 480 inpatient bed tertiary care hospital in India. Methods Plasma voriconazole estimation was done in seventy-two patients on standard weight based voriconazole therapy by High Performance Liquid Chromatography (HPLC) while genotype assessment for the CYP2C19*2 and *3 was done by PCR–RFLP and *17 by ARMS-PCR. Statistical analysis and genotype-phenotype correlation was done by comparing the drug levels with the CYP2C19 genotype. Main outcome measure CYP2C19 polymorphisms influence voriconazole metabolism. Results A wide variability is seen in plasma levels with only 51 % attaining therapeutic levels. The allele frequency of *2, *3 and *17 variant were found to be 33.3, 0.7 and 18 % respectively. The drug levels in carriers of *2 allele (poor metabolizers) was twofold higher than that in extensive metabolizers. However, the influence of *2 allele was compromised in presence of *17 allele and patients had low voriconazole levels. In addition to the genotype, co-medication and clinical condition remarkably influenced voriconazole concentration. Conclusion Plasma voriconazole levels are influenced by CYP2C19 variants, drug interactions and clinical condition of the patient. Genotype assessment at initiation of therapy followed by drug monitoring would help optimizing therapeutic efficacy and minimizing toxicity. © 2015, Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie. Source

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