Dynamics of ampicillin-resistant Enterococcus faecium clones colonizing hospitalized patients: data from a prospective observational study

Abstract

Background: Little is known about the dynamics of colonizing Enterococcus faecium clones during hospitalization, invasive infection and after discharge.

Methods: In a prospective observational study we compared intestinal E. faecium colonization in three patient cohorts: 1) Patients from the Hematology Unit at the University Hospital Basel (UHBS), Switzerland, were investigated by weekly rectal swabs (RS) during hospitalization (group 1a, n = 33) and monthly after discharge (group 1b, n = 21). 2) Patients from the Intensive Care Unit (ICU) at the University Medical Center Utrecht, the Netherlands (group 2, n = 25) were swabbed weekly. 3) Patients with invasive E. faecium infection at UHBS were swabbed at the time of infection (group 3, n = 22). From each RS five colonies with typical E. faecium morphology were picked. Species identification was confirmed by PCR and ampicillin-resistant E. faecium (ARE) isolates were typed using Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). The Simpson's Index of Diversity (SID) was calculated.

Results: Out of 558 ARE isolates from 354 RS, MT159 was the most prevalent clone (54%, 100%, 52% and 83% of ARE in groups 1a, 1b, 2 and 3, respectively). Among hematological inpatients 13 (40%) had ARE. During hospitalization, the SID of MLVA-typed ARE decreased from 0.745 [95%CI 0.657-0.833] in week 1 to 0.513 [95%CI 0.388-0.637] in week 3. After discharge the only detected ARE was MT159 in 3 patients. In the ICU (group 2) almost all patients (84%) were colonized with ARE. The SID increased significantly from 0.373 [95%CI 0.175-0.572] at week 1 to a maximum of 0.808 [95%CI 0.768-0.849] at week 3 due to acquisition of multiple ARE clones. All 16 patients with invasive ARE were colonized with the same MLVA clone (p < 0.001).

Conclusions: In hospitalized high-risk patients MT159 is the most frequent colonizer and cause of invasive E. faecium infections. During hospitalization, ASE are quickly replaced by ARE. Diversity of ARE increases on units with possible cross-transmission such as ICUs. After hospitalization ARE are lost with the exception of MT159. In invasive infections, the invasive clone is the predominant gut colonizer.

Figure 1

Dynamics of colonizing E. faecium clones. Bars indicate the proportion of E. faecium isolates among the collected isolates at different time points; black color indicates MT159 clones, dark grey ampicillin-resistant non-MT159 clones and white color indicates ampicillin- susceptible non-typed E. faecium isolates. The black line shows the Simpson's index of diversity for ARE during the first 4 weeks in hospitalized patients and during months 1 & 2, 3 & 4 and 5, 6 & 7 in hematological outpatients. Confidence intervals are indicated in the text. Numbers of swabs are shown below the graph. Fluctuation in numbers of swabs is due to missing admission swabs in 8 hospitalizations (in which patients have been on the ward before start of the study), to discharge of patients at different time points and to lack of 3 swabs during hospitalization.