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416


Table 2. Baseline Characteristics of Patients With VRE Infectiona Versus Colonizationb


Variable


Age, mean y (SD) Female, % Race, % White Black


Hispanic Asian Other


Missing


Underlying diagnosis, % Leukemia/Lymphoma Sickle cell disease HIV infection


Congenital immunodeficiency


Other


HSCT transplant, % >1 transplant, %


Mortality, % deceased


Colonized (n=217)


45.2


Infected (n=133)


48.1 Total (n=350) P Value


45.6 (17.4) 42.3 (16.9) 44.4 (17.3) .08c .66d .96d


46.3


51.2 22.6 19.4 4.2 2.3 0.5


87.5 3.3 4.0 4.6


0.66


52.1 15.2 38.3


51.1 25.6 18.8 3.0 1.5 0.0


88.9 0.0 0.0 9.1


2.0


57.9 24.1 60.2


51.1 23.7 19.1 3.7 2.0 0.3


.03d


88.1 2.0 2.4 6.4


1.2


54.3 18.6 46.6


Note. VRE, vancomycin-resistant Enterococcus; SD, standard deviation. aVRE growth in culture from a clinical specimen other than urine. bVRE detection/growth in surveillance or urine culture. cStudent t test. dFisher exact test.


.32d .05d


<.0001d PCR-positive/Culture-negative analysis


Among the 84 PCRþ/Cx− patients, 75 had subsequent swabs col- lected. Only 23 (30%) of these 75 patients ever grewVREin culture.


The remaining patients’ PCRþ/Cx− swabs grew 41 other isolates (Fig. 1). PCR had a positive predictive value of 39%, and 95% of the identified organisms were not VRE.


VRE infection


Of the 350 patients included in this study, 133 developed a VRE infection. A significantly higher rate of infection was observed in patients whose initial detection was from a positive clinical


culture (67%) or PCRþ/Cxþ swab (32%) than in patients with PCRþ/Cx− swabs (8%).


2-sided P value < .05. The Kaplan-Meier survival curve P values were calculated using log-rank tests.


Results Overall cohort results


Between 2007 and 2015, 350 patients were identified as either colonized or infected with VRE. Most patients had an underlying diagnosis of leukemia or lymphoma (88%), and 54% had under- gone HSCT. Patients with a VRE infection had a higher mortality rate than those who were colonized (60% vs 38%). Patient charac- teristics and comparisons are summarized in Table 1 and Table 2.


Active surveillance results


Surveillance perirectal swabs identified VRE colonization in 230 of the 350 patients (66%): 146 had positive VRE PCR and culture


(PCRþ/Cxþ), and 84 had positive VRE PCR but negative culture (PCRþ/Cx−). No patients had negative PCR and positive culture (PCR−/Cxþ).


Clinical culture results


Clinical cultures growing VRE were the first manifestation of VRE acquisition in 120 patients: 54 (45%) in urine, 28 (23%) in blood, 25 (21%) in wounds and 13 (11%) other sources.


Subcohort analysis of VRE recolonization Among the 350 patients, 72 (23%) eventually met decolonization criteria, but 21 (29%) later became recolonized with VRE. Most recolonized patients had leukemia or lymphoma, and the majority had undergone HSCT (Table 3). Nearly all patients received inpatient antibiotics in the interval


after VRE decolonization (Table 3). Median total antibiotic days per VRE decolonized days and median antianaerobic antibi- otic days per VRE decolonized days were 3.5 and 5.6 times higher, respectively, in recolonized patients than among those who remained decolonized. Crude and adjusted hazard ratios of time to VRE recolonization


are presented in Table 4. After adjusting for median percentage of inpatient days in the final model, the hazard ofVRE recolonization was 4.3-fold higher (P=.001) in patients whose percentage of total antibiotic days was higher than the subcohort median. These relationships are graphically represented in Kaplan-Meier curve estimates in Figure 2.


Discussion


Our cohort of patients with VRE infection and colonization largely comprised patients who had underlying hematologic malignancies and/or had undergone HSCT, similar to previous reports.16 Only 15% of 350 patients appeared to become decolonized over the course of this study; this finding underscores the tenacity of VRE colonization. In our population, higher rates of VRE infection were seen in culture-positive colonized patients than culture-negative


Fig. 1. Organisms cultured from swabs that were PCR positive and culture negative


(PCRþ/Cx−) for VRE (n= 75). Among 84 patients whose surveillance swabs were PCRþ/Cx−, 75 had subsequent swabs collected. Of these 75 patients, 23 (30%) later grew VRE in culture from surveillance swabs, while the remaining patients’ swabs


(n=52) grew 41 other isolates: vancomycin-susceptible (vanco S) E. faecium/faecalis (27%), vancomycin-resistant (vanco R) E. faecalis (5%), E. gallinarum/casseliflavus (44%), and others (24%).


Heather Y. Hughes et al


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