nocosomial infection with vancomycin-dependent enterococci michelle nguyen bioc 230 10/11/04
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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.