| dc.description.abstract | BACKGROUND: Carbapenem drugs are the last resort antibacterial agents used in the treatment of Extended Spectrum Beta-Lactamase multi drug resistant Gram negative bacterial infections. Resistance to these drugs is reported to be predominantly due to production of carbapenemase enzymes encoded by Carbapenem Resistance Determining Genes (CRDGs). Various studies have shown that some bacteria which possess these genes appear phenotypically susceptible to carbapenems, suggesting that not all reported genes mediate resistance. However, data remains limited on the CRDGs frequently associated with phenotypic resistance to carbapenems among E. coli and K. pneumoniae isolates.AIM. To explore the association between CRDGs and phenotypic resistance to carbapenems in E. coli and K. pneumoniae. METHODS. This was a case control study involving 168 previously stored E. coli and K. pneumoniae isolates. Cases included the phenotypically carbapenem resistant isolates and controls the susceptible isolates, while the exposure factor was presence of one or more CRDGs. RESULTS. Of the 168 isolates, 13 were phenotypically resistant to imipenem (IMP), meropenem (MEM) and ertapenem (ERT) while 155 were susceptible. Of the 13 resistant isolates, only 3 had the CRDGs (blaNDM and blaOXA_48). Of the 155 susceptible isolates, 10 had one or two CRDGs (i.e. four with blaOXA_48, two with blaNDM, two with blaOXA_48, one with blaOXA_48 and blaNDM, and one with blaKPC and blaOXA_48).Overall, the odds ratio (O.R) between presence of any CRDGs and the phenotypic resistance to carbapenems was 8.1 (p-value 0.002). Based on individual CRDGs, the O.R between blaNDM and phenotypic resistance to IMP, MEM, and ERT was 11.4 (p-value0.0021), 21.1 (p-value0.0000), and 7.9 (p-value 0.045), respectively. The O.R between blaOXA_48 and phenotypic resistance to IMP and MEM was 2.5 (p-value= 0.40) and 4.31 (p-value= 0.17), respectively. The mean Zone Diameter (MZD) of isolates with CRDGs but phenotypically susceptible to IMP or ERT was 27 mm and 29 mm while that of isolates without the CRDGs was 26mm and 28mm, respectively. For MEM, the MZD was the same at 29 mm for both groups of susceptible isolates with/without the CRDGs. Lastly, the MZD of the 23 isolates that were initially resistant to IMP/MEM but turned susceptible upon sub culturing and repeating the sensitivity testing retesting changed from 17-18 mm (Resistant phenotype according to CLSI) before freezing to 27-28mm (susceptible phenotype) after a freezer-storage period of 2 – 36 months. CONCLUSION. Except for blaNDM, presence of the other CRDGs was inconsistently associated with phenotypic resistance to carbapenems. For the phenotypically carbapenem-susceptible E. coli or K. pneumoniae there was no significant difference between the mean Zone Diameters of isolates with the CRDGs Vs those without. For MEM, the MZD was the same at 29 mm for both groups of susceptible isolates with/without the CRDGs. Our findings also show that freezer-storage of carbapenem resistant E. coli or K. pneumoniae changed 82.1% of the resistant isolates to susceptible status. RECOMMENDATION. Based on our findings, using CRDGs to diagnose carbapenem resistance may not be appropriate. Both phenotypic and genotypic resistance to carbapenems requires further study to determine the true association between CRDGs and phenotypic carbapenem resistance. The change of from resistant to susceptible status during freezer-storage warranties further molecular studies to determine the underlying factors. | en_US |
