MEROPENEM INDUCED REDUCTION IN SERUM VALPROATE LEVEL- A CASE REPORT

Objective: To report a case of meropenem induced reduction in serum valproate level. Methods: The clinical data of an epileptic patient who experienced a decrease in seizure control due to a drug interaction between valproate and meropenem is described.Results: The patient was a 26 years old male who was a known case of refractory focal epilepsy and underwent surgery for the same. This patient was on five antiepileptic drugs including valproate. On treatment with meropenem for the management of post surgical site infection due to multidrug resistant Klebsiella pneumoniae, the patient experienced seizures due to decline in valproate level. Increasing the dose of valproate could not control the seizures. However, changing the antibiotics to a non carbapenem controlled the seizures.Conclusion: The present report highlights the potential drug interaction between valproate and meropenem. Physicians should thus avoid co-administration of both these agents. If concomitant administration is essential, close monitoring of valproate concentration and clinical monitoring for breakthrough seizures are necessitated.Â

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Abstract: Drug-resistant tuberculosis (TB), one of the leading causes of death worldwide, arises mainly from spontaneous mutations in the genome of Mycobacterium tuberculosis. There is an urgent need to understand the mechanisms by which the mutations confer resistance in order to identify new drug targets and to design new drugs. Previous studies have reported numerous mutations that confer resistance to anti-TB drugs, but there has been little systematic analysis to understand their genetic background and the potential impacts on the drug target stability and/or interactions. Here, we report the analysis of whole-genome sequence data for 98 clinical M. tuberculosis isolates from a city in southern India. The collection was screened for phenotypic resistance and sequenced to mine the genetic mutations conferring resistance to isoniazid and rifampicin. The most frequent mutation among isoniazid and rifampicin isolates was S315T in katG and S450L in rpoB respectively. The impacts of mutations on protein stability, protein-protein interactions and protein-ligand interactions were analysed using both statistical and machine-learning approaches. Drug-resistant mutations were predicted not only to target active sites in an orthosteric manner, but also to act through allosteric mechanisms arising from distant sites, sometimes at the protein-protein interface