Characterization of Ertapenem-non-Susceptible Klebsiella pneumoniae Isolates in a University Hospital in Southern Taiwan

• Main Authors: Li-RongWang, 王梨容
• Other Authors: Jing-Jou Yan
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/47616246324910135974

碩士 === 國立成功大學 === 醫學檢驗生物技術學系碩博士班 === 98 === Carbapenems (ertapenem, imipenem and meropenem) are the drugs of choice for the treatment of severe infections caused by multidrug-resistant AmpC- or extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolates, and the emergence of carbapenem resistance is a growing threat to patients. Bacteria resistant to ertapenem may appear susceptible to imipenem and meropenem in routine susceptibility tests. This study was conducted to investigate the prevalence and characteristics of ertapenem-nonsusceptible (ETP-R) Klebsiella pneumoniae isolates at a Taiwanese hospital. Antimicrobial susceptibility testing with and without pump inhibitors, PCR and nucleotide sequencing of resistance genes and porins genes, genotyping with PFGE and SDS-PAGE of outer membrane proteins were performed. The prevalence of ertapenem nonsusceptibility among bloodstream isolates increased from 0% in 2001 to 13.6% in 2008. Eighty-two nonduplicate ETP-R isolates recovered from various specimens in 2008 were examined. Seventy-four (90.2%) isolates of them had extended-spectrum β-lactamases (CTX-M- and SHV-type), AmpC enzymes (DHA-1 and CMY-2) and IMP-8 metallo-β-lactamase alone or in combination, and a high prevalence (95.1%) of fluoroquinolone resistance accompanied by a high rate (90.2%) of plasmid-mediated quinolone resistance determinants (qnrS, qnrB and aac(6′)-Ib-cr) was observed. Eighteen ETP-R but imipenem-susceptible isolates with genetic diversity were compared with 18 imipenem-nonsusceptible isolates collected before 2008. All 36 isolates except 2 imipenem-nonsusceptible isolates showed decreased expression of OmpK35 and/or OmpK36, and there was no significant difference in the numbers of isolates with decreased expression and genetic disruptions of both porins between the two groups. Synergy experiments revealed no evidence of efflux action contributing to carbapenem resistance but suggest the existence of phenylalanine-arginine-β-naphthylamide-sensitive pumps conferring coresistance to fluoroquinolones and tigecycline. This study revealed a marked increase in the prevalence of ertapenem nonsusceptibility in K. pneumoniae over an 8-year period and suggests that imipenem resistance was mostly caused by unidentified resistance mechanisms in addition to β-lactamase production and decreased porin expression.