several studies have failed to identify vancomycin as a risk factor (148,149,152,154). The
HICPAC recommendations included a list of indications for use of vancomycin and a list of
contraindications for use of this antibiotic (164). A more recent publication from the CDC
reports on a study performed in cooperation with 20 hospitals in the NNIS system that joined
the Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Project. These hospitals
contributed data from 50 ICUs on grams of selected antibiotics used each month and on
susceptibility tests for selected microorganisms recovered from patients in these units each
month (180). The data submitted to Project ICARE was used to create benchmarks for
vancomycin use. Those ICUs that instituted changes in practice observed significant decreases
in vancomycin use and in VRE prevalence. Although some controversy remains about whether
vancomycin use is a risk factor for acquisition of VRE, the bulk of the data to date is in favor of
limiting vancomycin use in ICUs as part of control programs for VRE.
Other antibiotics that have been identified as risk factors for acquisition of VRE include
cephalosporins, metronidazole, carbapenems, ticarcillin–clavulanate, and quinolones
(148,149,154,155). A study of the effect of antimicrobial therapy on the concentration of VRE
in patients’ stools observed that concentrations of VRE increased significantly in stools of those
patients who received antianaerobic antibiotics. The authors made the point that vancomycin
has antianaerobic activity and showed that VRE increased in concentration in stools of patients
who were treated with vancomycin (157). The authors also showed that patients with high
concentrations of VRE in stools caused greater environmental contamination and observed
that eight patients with VRE cultured from blood, urine, and a sacral wound had greater than
six logs of VRE per gram of stool. Therefore, avoiding the use of antianaerobic antimicrobial
therapy in patients when possible may aid in control of VRE by reducing environmental
contamination. Limiting the concentration of VRE in stool may also reduce the risk of invasive
disease due to VRE. Limiting the use of antianaerobic agents and vancomycin appears
important in the control of VRE.
Another approach to controlling VRE through changes in the use of antimicrobial agents
is to replace the use of antimicrobials to which VRE are resistant with antimicrobials to which
VRE are more susceptible. Piperacillin/tazobactam has been considered to be a good candidate
for suppressing the growth of VRE, because it has good antimicrobial activity against
E. faecium, which is the most common VRE species, and because it is concentrated in bile. Six
studies on the use of piperacillin–tazobactam in place of third-generation cephalosporins and
ticarcillin–clavulanate have been published (181–186). One study found no difference between
patients treated with cefepime and those treated with piperacillin–tazobactam in the
acquisition of VRE (186). However, there were several significant differences between the
two groups and the authors did not apply multivariable analysis to obtain a clearly un-
confounded conclusion of their results. Only one of the latter studies was adequately designed
to provide definitive results (185). There was a significant reduction in the acquisition of VRE
after ticarcillin–clavulanate was replaced by piperacillin–tazobactam. As the authors pointed
out, additional studies are needed for this control strategy as the study was carried out in a
single institution and the reduction in acquisition of VRE was associated with the formulary
change, but causality could not be established. When other measures have failed to control the
spread of VRE, this approach could be tried.
In summary when measures are being instituted in an attempt to control VRE, it would
appear prudent to limit the use of vancomycin, cephalosporins, metronidazole, clindamycin,
and ticarcillin–clavulanate. Initiating the use of piperacillin–tazobactam might add to the
effectiveness of manipulating antimicrobials as part of the control measures for VRE.
Other risk factors that should be addressed are the use of enteric feedings, the use of
antacids, and effectively removing VRE from environmental surfaces. Table 6 lists the control
measures for VRE in ICUs.
Cost Effectiveness of VRE Control
The high cost of VRE control is often mentioned in the literature, and many infection control
programs have decided to apply very limited control measures to prevent and control the
spread of VRE. However, several recent studies on the cost-effectiveness of VRE control have
118 Mayhall