Nocosomial infection with Vancomycin-dependent Enterococci

Michelle Nguyen

Bioc 230

10/11/04

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Cases Molecular profiling of VDE Case control study Discussion

Case 1

32 y.o woman with h/o type 1 DM, ESRD Kidney-pancreas transplant Post-op infection with VR Enterococcus

faeciumTx with antibiotics Abdominal fluid culture VR E. faecium

that cannot grow w/o Vancomycin Refractory sepsisdeath (day 268)

Case #2

40 y.o woman with h/o type I DM, ESRD Kidney-pancreas transplant Post-op: VRE from intraabdominal

culturesremove kidney and pancreas Antibiotic tx with IV streptogramins Refractory VREdeath

Case #3

47 y.o woman with h/o CML Matched-unrelated donor bone marrow

transplant Post-op: severe GVHD, acute renal failure,

bacteremia with Corynebacteriumvancomycin

UTI with VREnot eradicated Death due to refractory GVHD with multiple

organ failure (day 87)

Tip off: what are the common points Nocosomial infections Comorbidities: DM, kidney

dysfunction,tranplants post-op complications Bacteremia with VDE Broad use of antibiotics and

immunosuppressive drugs (what are the risks??)

Characterizing VDE

Criteria VRE: growth in 6ug/ml Vancomycin, MIC>8ug/ml Vanco VDE: cannot growth without 6ug/ml Vanco with multiple

subcultures Molecular profile

Susceptibility testing: Vanco disk, D-ala-D-ala disk Resistance gene vanA and vanB: PCR Strain relation (distinct clones?): Pulsed-field gel

electrophoresis (PFGE) Spontaneous reversion from VDE to VRE: serial dilutions

of culture grown in Vanco+ broth to Vanco+/- agar plates

Susceptibility Test Result

VDE

Revertant

PFGE

Molecular profile of VDE

Strain: E. faecium Resistance gene: vanA (2), vanB (1) Resistance profile: penicillins, gentamicin,

erythromycin Susceptibility: streptogramins, teicoplanin Spontaneous reversion: around 1x10-6 except

for strain 3 (2.6x10-3) Growth not supported by D-ala-D-ala

Proposed mechanism for Vancomycin dependence Loss of D-ala-D-ala ligase in VRE strain Vancomycin induces production of D-ala-

D-lactate ligase Require prolonged exposure to

Vancomycin

Case control study

3 patients with nocosomial VDE infection 10 patients with nocosomial VRE infection 10 at-risk patients not infected with

enterococci Matched by age and admission to same

service

Typical case control study design

Case study results

Specific findings

Length of exposure to antimicrobialsVancomycin3rd generation cephalosporins

Mortality Gender Exposure to ICU

Possible risk factors

Intense use of 3rd generation cephalosporins

Renal insufficiency Spontaneous reversionVanco

discontinuation might not be sufficient to treat VDE infection.