Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients - PubMed (original) (raw)

Clinical Trial

. 2013 Oct;13(10):2619-33.

doi: 10.1111/ajt.12424. Epub 2013 Sep 6.

L Chen, R K Shields, Y Zhao, S Cheng, K D Chavda, B Hao, J H Hong, Y Doi, E J Kwak, F P Silveira, R Abdel-Massih, T Bogdanovich, A Humar, D S Perlin, B N Kreiswirth, M Hong Nguyen

Affiliations

Clinical Trial

Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients

C J Clancy et al. Am J Transplant. 2013 Oct.

Abstract

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.

Keywords: Bacteremia; Klebsiella pneumoniae; Klebsiella pneumoniae carbapenemase; ST258; transplantation.

© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

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Conflict of interest statement

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1

Figure 1. Summary of treatment and outcomes of transplant recipients with CR-Kp bacteremia

* *Patients who died of septic shock within 6 days were excluded because they either received an inactive agent (piperacillin-tazobactam; P2) or received a regimen with a single active agent for only 1 day (P1 and P3). CR-Kp, carbapenem-resistant Klebsiella pneumoniae; n, number; (I), intermediate; (R), resistant.

Figure 2

Figure 2. Distribution of doripenem MICs and ompK36 variants

Doripenem was chosen to represent the carbapenem class since it is the formulary agent at our center. MICs, minimum inhibitory concentrations.

Figure 3

Figure 3. PFGE of representative KPC-Kp isolates from the 17 patients with bacteremia

PFGE dendrogramshowing the relatedness of 41 KPC-producing K. pneumoniae isolates. All KPC-2-producing ST258 strains were clustered in one group, sharing >86.5% similarities. KPC-3-producing ST37 strains were distinct from ST258 strains (<65% similarities). The numbers following the abbreviations for the patients’ samples correspond to days before (number preceded by a minus sign) or after the first positive blood culture (number alone). For example, U-90 denotes urine culture obtained 90 days before the first positive blood culture. B0 denotes the first positive blood culture. T24 denotes tissue culture obtained 24 days after the first positive blood culture. PFGE, pulse-field gel electrophoresis; KPC-K. pneumoniae (KPC-Kp).

Figure 4

Figure 4. Serial ST258, KPC-2-producing strains with ompK36 variants isolated from an intestinal transplant recipient with persistent bacteremia (P9)

Blue and red diamonds represent bloodstream and non-bloodstream strains, respectively.

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