ongoing MRSA carriage prevalence in admitted patients of 4%, the authors were able to reduce
the incidence of ICU-acquired MRSA infection and colonization by fourfold. They observed
that costs for single-room isolation of patients were $1480 and that the extra cost of an MRSA
infection was $9275. They estimated that control was cost-effective when MRSA carriage on
admission is between 1% and 7% and when the MRSA transmission rate from colonized to
isolated patients is at least fivefold less than to patients not isolated. Additional studies are
needed on the cost-effectiveness of MRSA control.
VANCOMYCIN-RESISTANT ENTEROCOCCI
Mechanism of Resistance
Although there are many species ofEnterococcus, relatively few species make up the VRE that
cause endemic and epidemic nosocomial colonization and infection in health care facilities.
The most important species are Enterococcus faeciumandEnterococcus faecalis. Two other
species,Enterococcus gallinariumandEnterococcus casseliflavus, are motile and display intrinsic
vancomycin resistance (118).
Vancomycin resistance in enterococci is mediated by the production ofD-Alanine:D-
Alanine ligases of altered substrate specificity (119). The most common ligases with altered
substrate specificity arevanAandvanB. Both of these ligases condenseD-Ala withD-Lac
(lactate). Vancomycin does not bind toD-Lac, thus permitting cell wall synthesis to continue.
ThevanAtrait is carried on a transposon Tn 1546. This transposon is most often carried on a
plasmid and can be transferred to other gram-positive cocci. The genes that code for bothvanA
andvanBare similar. ThevanBgenes are carried on a large mobile element found on the
chromosome. ThevanBtrait can be transferred to other enterococci (118). VRE containing the
vanAligase are resistant to vancomycin and another glycopeptide, telcoplanin, whereasvanB
isolates are resistant to vancomycin but are susceptible to telcoplanin. Enterococci carrying
vanAhave minimal inhibitory concentrations (MICs) to vancomycin of> 64 mg/mL, whereas
isolates withvanBhave MICs to vancomycin of 16 to> 1000 mg/mL (118).
Other types of ligases with altered substrate specificities arevanC[D-Ala-D-Ser (serine)],
vanD(D-Ala-D-Lac), andvanE(D-Ala-D-Ser). ThevanEgenes are found on the chromosomes of
E. gallinariumandE. casseliflavus. These latter species have intrinsic low-level resistance to
vancomycin (8 to 16mg/mL).
More recently, it has been discovered thatE. faeciumstrains of VRE have acquired genes
that appear to code for two virulence factors (120,121). Theespgene was found only in
outbreak strains ofE. faeciumon three continents and not in nonepidemic isolates and isolates
from healthy individuals or farm animals (120). Isolates carrying theespgene seem to be
associated with in-hospital spread and possibly with increased virulence. ThehylEfmgene is
found primarily in vancomycin-resistantE. faeciumin nonstool cultures obtained from patients
hospitalized in the United States (121). This observation suggests that specificE. faeciumstrains
may contain determinants that are associated with clinical infections. The appearance of
virulence determinants in microorganisms that were considered nonvirulent normal flora in
the past makes control of VRE even more urgent than when the only concern was resistance to
glycopeptides.
Types of Infections Caused by VRE
Adult ICUs
The most important type of infection caused by VRE is bacteremia. Such infections are
usually related to intravascular catheters (122–128). Mortality due to VRE bacteremia has not
been studied extensively. One study concluded that VRE bacteremia had a negative impact
on survival (126). The best study was a historical cohort study that found an attributable
mortality of 37% (95% CI 10% to 64%) (125). Nosocomial meningitis has been reported rarely
(129,130). VRE is frequently cultured from urine, but only about 13% of patients with positive
urine cultures have a urinary tract infection. Bacteremia from the infected urinary tract occurs
but is uncommon (131). A univariate analysis of patients with and without a urinary tract
infection revealed a significant relationship between having a malignancy and a urinary
tract infection (131).
112 Mayhall