High prevalence of carbapenem resistance among plasmid-mediated AmpC β-lactamase-producing Klebsiella pneumoniae during outbreaks in liver transplantation units.

During a prospective surveillance using PCR for the detection of plasmid-mediated AmpC β-lactamase (pAmpC)-producing Enterobacteriaceae, outbreaks due to pAmpC-producing Klebsiella pneumoniae (pAmpC-Kp) occurred in an adult liver transplantation unit (aLTU) and a paediatric liver transplantation unit (pLTU), with carbapenem-resistant (CR) variants. Between April 2010 and March 2012, a total of 32 patients infected with pAmpC-Kp were found by prospective surveillance using PCR detection at a Japanese university hospital. Multilocus sequence typing, analysis of outer membrane proteins, and detection of carbapenemases were performed. Clinical courses of patients with bloodstream infection (BSI) were reviewed. Of 32 pAmpC-Kp isolates from each patient, 20 (18 from aLTU patients) were DHA-1-producing sequence type 11 (DHA-1-ST11), 9 were CMY-2-ST45/778 (all from pLTU patients) and the other 3 isolates had different sequence types. CR variants were isolated from 8 aLTU patients with DHA-1-ST11 and from 1 pLTU patient with CMY-2-ST45. All of the pAmpC-Kp isolates, including CR variants, were negative for carbapenemases. All of the DHA-1-ST11 and CMY-2-ST45 isolates lacked OmpK35, and seven CR variants also lacked OmpK36. BSIs due to DHA-1-ST11 isolates, including CR variants, occurred in six aLTU patients, four of whom died. The outbreaks were controlled after application of intensified infection control measures. During pAmpC-Kp outbreaks involving 27 liver transplants, CR variants with porin loss developed in nine patients, and DHA-1-ST11 K. pneumoniae caused BSIs with high mortality.