VRE comes up often in this exam:
- Question 2 from the second paper of 2012
- Question 30 from the first paper of 2012
- Question 26 from the first paper of 2007
- Question 9 from the second paper of 2004
- Question 1b from the first paper of 2004
LITFL have a CCC chapter on VRE which covers this topic with characteristic clarity.
If one were a time-poor CICM exam candidate in need of a single all-encompassing literature reference for this topic, this article from Clinical Microbiology Reviews (2000) would satisfy that need. On the other hand, if one were a total microbiology fiend with no life, one could derive a great deal of enjoyment from Barbara Murray's "The Life and Times of the Enterococcus", from 1990.
Microbiology of VRE
Though initially included in the Streptococcus genus (they were the Lancefield Group D strep), in the 1980s enterococci were ultimately removed into their own genus on genetic grounds.
These cocci are intrinsically quite benign. They have low pathogenicity, forming a calm and law-abiding population in the human colon. In fact if you didn't have any enterococci in your stool you would be a rare individual; according to studies of faecal microflora 97% of the population excrete an enterococcus of some sort. The two clinically relevant species are E.faecalis and E.faecium, of which E. faecalis seems to be more common and tends to be found in higher numbers.
What is the clinical significance of the two species, you might ask?
|Factors associated with infection||
|Mortality from bacteraemia||
|Naive antibiotic susceptibility||
|Innate antibiotic resistances||
- E.faecium attacks debilitated patients, is more antibiotic-resistant in general, and specifically it is usually vancomycin-resistant.
- Quinupristin-dalfopristin (Synercid) kills E.faecium but not E.faecalis.
Mechanisms of antibiotic resistance among VRE organisms
Enterococci have intrinsic resistance to most β-lactam antibiotics (including carbapenems) due to the low affinity of their penicillin-binding proteins. Interestingly, piperacillin has approximately the same activity as benzylpenicillin against these enterococci; ticarcillin and cephalosporins have about four times less activity, and are thus essentially useless. Of the two species, E.faecium is the more β-lactam-resistant, whereas E.faecalis is frequently susceptible to ampicillin.
Enterococci may develop resistance to aminoglycosides by producing an inactivating enzyme (2-phosphotransferase-6-acetyltransferase). Generally speaking if they are resistant to gentamicin they will also be resistant to amikacin. If this enzyme is present, there will be no β-lactam-aminoglycoside synergy.
Vancomycin resistance: VanA and VanB phenotypes
These are mutants with vancomycin resistance.
A good table describing these phenotypes is available.
- Van A are teicoplanin-resistant, and vancomycin-resistant to an extreme degree.
- Van B are teicoplanin-sensitive, and modestly vancomycin-resistant.
Both VanA and VanB resistance can be transferred from one strain of enterococcus to another.
Of the two, VanA is the more widely distributed.
Resistance mechanism rests in the synthesis of abnormal D-Ala–D-lactate peptidoglycans, instead of the normal D-Ala–D-Ala (to which the vancomycin binds).
Risk factors for VRE colonisation:
These risk factors are listed by a 2012 Mebourne study, which was a cross-sectional assessment of colonisation prevalence in a tertiary hospital:
Consequences of VRE colonisation
- Need for isolation
- Potential for clinically significant VRE infection
- Potential for transmission of vancomycin resistance to S.aureus
Management of the VRE-colonised patient
- Protective equipment
- Scrupulous attention to cleaning areas where the patient has been
- Surveillance swabs until the patient tests negative
Management of the clinically relevant VRE infection
When offering their antibiotic suggestions, the Sanford Guide quoted this 2010 article as their main inspiration.
The activity of carbapenems againt either E.faecalis or E.faecium is apparently poor.
The clinical relevance of enterococcal bacteraemia
Question 1b from the first paper of 2004 doesn't go into VRE right away, but rather presents the candidate with some blood cultres which have grown E.faecalis. The 1988 article by Maki and Agger suggests that normally the enterococci are avirulent, meaning that in the healthy host their presence in the bloodstream is fairly benign. However, in the altered host (eg. a critically ill patient) they become opportunistic pathogens. Corresponding to this, the celebrated 1997 review by Weinstein et al remarks that "whereas pneumococci always represented real infection, enterococcal isolates did so only 70% of the time". In that review, enterococcal bacteraemia was not found to be a factor which influenced prognosis.