Prevalence of carbapenem resistance encoding genes and corresponding MIC90 in enterobacteriaceae at a tertiary medical care center in Lebanon

Background: The aim of this study was to correlate genes involved in carbapenem resistance to MIC levels among clinical ESBL and non-ESBL producing carbapenem resistant Enterobacteriaceae (CRE) isolates of Escherichia coli and Klebsiella pneumoniae. Materials and Methods: E. coli (n= 76) and K. pneumoniae (n=54), collected between July 2008 and July 2014, were analyzed. The MICs were determined against ertapenem (ERT), imipenem (IMP) and meropenem (MER). PCR was performed on all 130 isolates to amplify the resistance and outer membrane proteins (OMPs) encoding genes: bla OXA-48, blaNDM-1,blaTEM-1,blaCTX-M-15, ompCand ompF.Sequencing was performed on selected isolates.  Results: The prevalence of bla OXA-48, blaNDM-1,  blaTEM-1 and/or blaCTX-M-15 among E. coli isolates were 36%, 12%, 20% and 80%, respectively, while among K. pneumoniae they were 37%, 28%, 28% and 72%, respectively. K. pneumoniae isolates positive for any of these genes had an MIC90> 32µg/ml  against ERT, IMP and MER, while in E. coli isolates there was a variation in the MIC90 values. Porin impermeabilitieswere due to mutations in ompCand ompF genes in E. coli, and loss of ompCand ompF genes in K. pneumoniae,andincreased MIC90 values. The presence of more than one carbapenem resistance encoding gene and/ or ESBL encoding genedid not have an effect on the MIC90 value in K. pneumoniae isolates, while in E. coliit showed higher MIC90 values. Conclusion: Levels of MIC in CRE may largely depend on the type of resistance encoding genes, and porin impermeabilities. These resultsmay provide information for antibiotic regimen selection and epidemiological monitoring of resistance.