Fatal cross infection by carbapenem-resistant Klebsiella in two liver transplant recipients

Abstract

Members of the family Enterobacteriaceae including Klebsiella have re-emerged as major pathogens in solid organ transplantation. The recent appearance and dissemination of carbapenemase-producing Enterobacteriaceae in Europe and the northeastern United States represents a major challenge to the treatment of enteric gram-negative bacterial infections in immunocompromised patients; however, few reports have detailed the outcomes of such infections. Here we report 2 cases of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella infections in orthotopic liver transplant recipients, which were the index case and initial secondary case for an outbreak of KPC-producing Enterobacteriaceae in our institution. In both instances, the pathogens were initially misidentified as being carbapenem sensitive, the infections recurred after cessation of directed therapy, and the patients ultimately succumbed to their infections.

Fig. 1

Modified Hodge tests of K. pneumoniae isolates from patient 1. A 10-μg imipenem disk was placed in the center of a MHA plate shortly after being inoculated with the carbapenem-sensitive strain E. coli ATCC 25922, and isolates Kpn1014 and Kpn1016 were struck radially from the disk to the plate edge. Kpn1014 is bla_KPC-2-negative and shows a concentric zone of growth inhibition at its intersection with ATCC 25922, whereas invagination of ATCC 25922 growth into the imipenem zone of inhibition adjacent to Kpn1016 is indicative of carbapenemase production.

Fig. 2

(A) Plasmid DNA profiles of Klebsiella isolates from patient 1 (Kpn1014, Kpn1016, and Kox1015) and patient 2 (Kpn1017) resolved on a 0.6% agarose gel. E. coli V517 supercoiled plasmid standards (kb). C, chromosomal DNA. (B) Southern blot of the gel shown in panel A after hybridization with an 1009-bp bla_KPC-2-specific probe. DNA sequence-confirmed bla_KPC-2 PCR product (right-most lane) loaded one hour before completion of the electrophoresis served as the positive control.

Fig. 3

Pulsed-field gel electrophoresis profiles and dendrogram of XbaI macrorestricted chromosomal DNA fragments of the K. pneumoniae isolates from patient 1 (Kpn1014, Kpn1016), patient 2 (Kpn1017), and 22 additional KPC-producing K. pneumoniae isolates.