Infection Control & Hospital Epidemiology
history of VRE colonization and infection as well as the results of our investigation of whether receipt of inpatient antibiotics is associated with time to VRE recolonization.
Methods Patients and setting
All patients who had VRE infection or colonization identified from active surveillance or clinical cultures between January 2007 and December 2015 were included in the study. Starting in July 2009, surveillance perirectal swabs were collected on admission and then weekly from all patients receiving HSCT and on medical oncology wards (regardless of diagnosis), except those already known to be colonized with VRE. The institutional review board waived approval for this study.
Definitions
Patients met criteria forVRE infection if VRE grew in culture from a clinical specimen other than urine. Patients who had positive perirectal cultures or PCR for VRE or who had VRE grown from urine were considered colonized. Patients off antibiotics ≥4 weeks who had 3 consecutive negative perirectal swabs at least 1 week apart were considered decolonized. After they were decolonized, patients were classified as recolonized if they later had clinical cultures or surveillance swabs positive for VRE. Decolonized patients who had no further microbiological evidence of VRE were considered to have remained decolonized. The primary exposure variables were total antibiotic and anti-
anaerobic antibiotic days. An antibiotic day was defined as receipt of at least 1 inpatient antibiotic per 24-hour period. Outpatient antibiotics were excluded because we were unable to confirm administration definitively. Antibiotics most likely to be prescribed for intra-abdominal infections were included in the group of antianaerobic antibiotics. Ampicillin/sulbactam, amoxicillin/clav- ulanate, meropenem, imipenem, ertapenem, metronidazole, and piperacillin/tazobactam were classified as antianaerobic antibiot- ics. Because clindamycin is not recommended as a first-line anti- biotic for these infections, it was not included. Possible confounding variables were selected based on literature
review and clinician experience and included age at the timeofVRE decolonization, race, gender, and inpatient hospitalization days. The primary outcome variable was VRE recolonization. The at-
risk period was the duration of VRE decolonization, defined as the number of days between the first negative perirectal culture and the date of recolonization or the last known negative culture.
VRE screening and clinical cultures
Throughout the study period, clinical specimens were inoculated onto selective media (bile esculin azide agar containing 6 μg/mL vancomycin). From July 2009 to July 2010, perirectal swabs were also inoculated onto selective media. Starting in July 2010, swabs were first tested by rapid VanA/VanB PCR (Cepheid), which, due to low positive predictive value, was replaced in December 2010 with rapid VanA PCR (Cepheid). Swabs with positive PCR results were inoculated onto selective media. Colonies were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) and underwent automated antimicrobial susceptibility testing using the Phoenix (Becton Dickinson, Franklin Lakes, NJ) and Vitek (bioMèrieux, Marcy- l’Étoile, France) systems.
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Table 1. Baseline Characteristics of Patients With VRE Colonization and/or Infection
Characteristic
Age, mean y (SD) Age, median y (IQR) Female, no. (%)
Race, no. (%) White Black
Hispanic Asian Other
Missing
Underlying diagnosis, no. (%) Leukemia/lymphoma Sickle cell disease HIV
Immunodeficiency disorder Other
Receipt of transplant, no. (%)
Type of first transplant (%) Myeloablative HSCT
Reduced intensity HSCT Autologous HSCT
HSCT, type unknown Solid organ Not available
>1 transplant, % Mortality, no. (%) deceased
Total (n=350) 44.4 (17.3) 46 (29–59) 162 (46.3)
179 (51.1) 83 (23.7) 67 (19.1) 13 (3.7) 7 (2.0)
1 (0.29)
309 (88.3) 7 (2.0) 8 (2.3)
22 (6.3) 4 (1.1)
190 (54.3)
17.1 30.9 4.3
0.87 1.1
45.7 18.6
163 (46.6)
Note. SD, standard deviation; IQR, interquartile range; HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplant.
Statistical analysis
To standardize antibiotic exposure during the at-risk period, the median proportions of total antibiotic days per VRE decolonized days and antianaerobic antibiotic days per VRE decolonized days were calculated for each patient and analyzed in regression models. The median proportions of antibiotic days per VRE decolonized days were then analyzed separately in survival analyses as binary variables either above or below the respective medians. The pro- portion of inpatient days per VRE decolonized days was calculated for each patient then analyzed as a binary variable either above or below the respective subcohort (n=72) median. We used Stata version 13.1 statistical software (StataCorp,
College Station, TX) for all analyses. Baseline characteristics were compared using the Student t test for means and the Fisher exact test and the Pearson χ2 test for categorical values. Percentage of median total antibiotic days, antianaerobic antibiotic days, and in- patient hospital days were compared using the median Fisher exact test. Hazard ratios and significance determinations were calculated using Cox proportional hazards models with time-fixed covariates and robust estimation. Statistical significance was defined as a
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