Table 1. Vancomycin-resistant enterococci in hematopoietic stem cell transplant recipients: colonization, bacteremia, risk factors, and outcomes.
ALL, acute lymphocytic leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplant; AML, acute myeloid leukemia; auto-HSCT, autologous hematopoietic stem cell transplant; BJH, Barnes Jewish Hospital; BSI, bloodstream infection; Cdiff, Clostridium difficile; CML, chronic myeloid leukemia; CMV, cytomegalovirus; Colo, colonization; CS, comorbidity score; GC, glucocorticoid; GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; HR, hazard ratio; IS, immunosuppression; LOS, length of hospital stay; MAR, myeloablative regimen; MDACC, Monroe Dunaway Anderson Cancer Center; MDS, myelodysplastic syndrome; Mort (Colo), mortality in colonized patients; Mort (Colo to BSI), mortality in patients progressing from colonization to bloodstream infection; Mort (non-Colo), mortality in non-colonized patients; MSKCC, Memorial Sloan Kettering Cancer Center; OR, odds ratio; PBSC, peripheral blood stem cell; PCR, polymerase chain reaction; RF, risk factor; RR, relative risk; TBI, total body irradiation; UCB, umbilical cord blood; UConn, University of Connecticut Health Center; URD, unrelated donor; VRE, vancomycin-resistant enterococci; VSE, vancomycin sensitive enterococci.
| Study | Sample size,
type of HSCT, years of study |
Prophylactic
antibiotics? |
VRE
Screening |
Colonization
rate |
Risk factors | VRE BSI
incidence |
Progression
to VRE BSI |
Risk factors for
VRE BSI |
VRE BSI outcomes:
mortality (Mort), attributable mortality (Att Mort), and overall survival (OS) |
|---|---|---|---|---|---|---|---|---|---|
| Kapur
et al.
16
2000 UConn |
321
Auto-HSCT 1993–1998 |
Yes | Rectal swab
or stool culture weekly |
50% (15/29) | - | 3% | 27% | - | Mort: 70%
Att Mort: 10% |
| Almyroudis
et al.
11
2005 MSKCC |
298
(adult and children) HSCT 1999–2003 |
No | - | - | - | Pre-engraftment:
22% (25.7% in adults) Post-engraftment: 19.5% |
- | Pre-engraftment:
CML (OR=4.13, P = 0.001) PBSCs (OR=1.8, P = 0.04) Post-engraftment: GVHD 2–4 (OR 4.8, P <0.0001), neutropenia (OR 3.4, P = 0.002), GCs (OR 3.2, P <0.0001), kidney failure (OR 3.8, P = 0.003), liver failure (OR 3.8, P <0.0001) |
Pre-engraftment:
Mort: 20.3% Att Mort: 14% OS in BSI versus no BSI (46.8% versus 64.1%, P <0.01) Post-engraftment: Mort: 17.2% Att Mort: 0 OS BSI versus no BSI (55% versus 63.3%, P = 0.25) |
| Avery
et al.
15
*
2005 Cleveland Clinic |
281
Allo-HSCT 1997–2003 |
No | No | - | - | 4.3% | URD | Mort: 100%
Att Mort: 10% |
|
| Matar
et al.
5
2006 MDACC |
653
HSCT 2001 |
Stool culture
weekly x3 |
4.7% | N/A | 1.4% | 28% (9/32) | - | Att Mort: 7% | |
| Dubberke
et al.
23
*
2006 BJH |
968 auto-
HSCT; 612 allo-HSCT 1996–2002 |
No * | Stool culture in
patients tested for Cdiff |
21% | - | 3.9% | 13% (42/334) | - | Mort: 53%
Att Mort: 12.5% |
| Zirakzadeh
et al.
17
2008 Mayo Clinic |
217 allo-HSCT
1998–2004 |
Yes | pre-HSCT
swab or stool culture or PCR twice weekly and with diarrhea |
10% | Cdiff, renal
failure, AML, low platelet count, TBI, MAR |
2.8% | 27% (6/22) | Colo (27% versus
0%, P≤0.01) |
Mort: 27.6%
Mort (Colo): 45% Mort (non-Colo): 25% (HR 2.1, P = 0.028) Mort (Colo to BSI): 83% |
| Weinstock
et al.
12
2007 MSKCC |
92 allo-HSCT
2004–2006 |
Yes * | Stool culture on
admission for HSCT and also with diarrhea |
40%
Pre-HSCT n = 2, at HSCT n = 25, and post- HSCT n = 10 |
Acute
leukemia, refractory anemia with excess blasts |
15% (14/92) | 4% (13/37)
27% (10/37) pre-HSCT |
Colo (34% versus
1.8%, P <0.01) |
Mort: 50%
Att Mort: 14.3% Mort for VRE BSI versus other BSI (HR 5.1, P = 0.5) Mort (non-Colo) versus Mort (Colo non- progressors) (HR 0.8, P = 0.55) |
| Kamboj
et al.
7
2010 MSKCC |
247
allo-HSCT 2008–2009 |
Yes * | Rectal swab
culture weekly |
27.5% | 11% 13/23
(57%) were colonized |
19% (13/68) | pre-HSCT Colo
(OR=3.88, P = 0.005) T cell depletion (OR=10.89, P = 0.028) |
Mort in VRE BSI
versus non-VRE BSI versus no BSI 4.4% versus 15% versus 2% Att Mort: 9% |
|
| Vydra
et al.
18
2012 University of Minnesota |
752
HSCT 491 adults 2004–2008 |
N/A | Perirectal swab
cultures weekly |
23%
6% (43/752) pre-HSCT |
Leukemia
MDS Age >60 |
8% ** | 14% | pre-HSCT Colo
RR=3.3 ( P = 0.01) post-HSCT Colo RR=7.7 ( P <0.01) Engraftment delay acute GVHD 3–4 |
Mort
**: 38%
OS VRE BSI versus VSE BSI: 23% versus 48% ( P = 0.04) |
| Kang
et al.
10
2013 University of Chicago |
152
HSCT 2008–2011 |
Yes | Rectal swab
weekly cultures |
100% | 12.5% | vancomycin
( P = 0.017), prolonged neutropenia ( P = 0.001), IS ( P <0.001), VRE at week 1 ( P = 0.05) *** |
Non-progressors
versus progressors Mort: 4% versus 29% ( P = 0.001) |
||
| Tavadze
et al.
6
2014 Cleveland Clinic |
800
Allo-HSCT 1997–2011 |
- | No | - | - | 9.5%
17% (n = 13) previous VRE or Colo |
Later year of HSCT
(HR=1.06, P = 0.037) High HSCT-CS (HR=2.02, P = 0.022) ALL (HR=2.20, P = 0.003) URD (HR=2.75, P <0.001) UCB donor (HR=3.11, P = 0.003) |
Mort: 96%
Att Mort: 5% Worse OS: VRE BSI (HR=4.45, p<0.001) Year of transplant Male gender Older age Prior chemotherapies High HSCT-CS Lack of remission at HSCT URD CMV- positive donor |
|
| Satlin
et al.
13
2014 Weill Cornell University |
238
allo-HSCT 287 auto-SCT 2007–2011 |
Yes | No | - | - | Allo-HSCT:
16.4% Auto-HSCT: 3.8% |
- | Mismatched PBSCs
(HR=3.76, P = 0.04) Time to engraftment (HR=1.06 per day, 95%, P = 0.005) |
Mort: 18% |
| Ford
et al.
27
2015 Salt Lake City |
300 auto-HSCT
2006–2013 |
Yes | Stool cultures
on admission and weekly |
36% | Lymphoma | 3% | 8.3% (9/108) | Colo | Mort: 0 |
| Ford
et al.
8
2017 Salt Lake City |
161
HSCT |
Yes | Stool cultures
on admission and weekly |
pre-HSCT:
61% (66/109) day of HSCT: 43% (58/134) |
Time from
leukemia to HSCT Pre-HSCT Colo: RF of subsequent Colo (HR=3.8) |
12%
Pre- engraftment (10) Post- engraftment (9) |
10% (at day 30)
12.5% (at day 90) |
Pre-engraftment:
Pre-HSCT Colo Colo at admission Post-engraftment: GVHD Pre-HSCT Colo |
Pre-engraftment Mort:
20% Similar OS in VRE BSI versus other BSI Worse OS: All BSI (HR=3.6, P <0.006) Post-engraftment VRE BSI versus pre- engraftment VRE BSI (10% versus 80%, P = 0.0007) No influence of Colo on LOS or OS, trend to greater healthcare costs |
| Hefazi
et al.
9
2016 Mayo Clinic |
203 AML
Allo-HSCT 2004–2014 |
No | Perirectal or
stool PCR on day 0 and twice weekly |
Day 0: 36%
Day 1–100: 10% >Day 100: 8% |
HSCT-CS ≥3 | Day 0–30: 5%
91% (10) were colonized Day 30–100: 0.4% (1) >Day 100: 4% |
11% (10/88) | Age ≥60 (
P = 0.04)
HSCT-CS ≥3 ( P = 0.03) Colo ( P = 0.003) |
Mort: 55% (6/11), 9%
within 100 days Att Mort: 0 Pre-HSCT VRE Colo no impact on outcomes/OS Colo after day 0 associated with worse survival (HR=2.2, P = 0.03) |
*Studies in which all individuals developing febrile neutropenia were automatically started on empirical vancomycin
**Specific data observed in adults
***Colonization, prior VRE, or delayed engraftment were not risk factors