Vancomycin-resistant enterococci

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Enterococcus faecalis and E. faecium inhabit the gastrointestinal tract and tolerate harsh environmental conditions. E. faecium causing healthcare infection is commonly ampicillin resistant and may acquire glycopeptide resistance. vanA usually causes resistance to vancomycin and teicoplanin; vanB confers variable vancomycin resistance while teicoplanin may remain active in vitro, but definitive treatment still requires full susceptibility and specialist interpretation.

Risk factors include prolonged admission, critical care, haematology or transplantation, broad cephalosporin, glycopeptide or anti-anaerobic antibiotic exposure, gastrointestinal surgery, biliary or urinary instrumentation, central access, renal failure and colonisation pressure. Antibiotics suppress competing bowel flora and allow VRE density to rise, increasing both transmission and invasion.

The central clinical distinction is carriage versus infection. Enterococci in a mixed superficial swab or catheter urine may not explain illness. By contrast, repeated blood isolates, sterile-site growth or concordant sepsis and source findings require prompt therapy. Source control frequently determines outcome because enterococci form biofilm on lines, valves and implanted material.

Key points

Enterococci normally colonise the bowel. VRE or glycopeptide-resistant enterococci are usually E. faecium carrying vanA or vanB, although other species and intrinsic resistance occur.
A positive rectal screen, stool culture, chronic wound or asymptomatic catheter urine usually represents carriage and does not require systemic antibiotic treatment.
Bloodstream isolation is always significant. Obtain cultures before treatment when safe, repeat until clearance and identify central-line, biliary, urinary, abdominal, valve or prosthetic sources.
Species and full susceptibility matter: vancomycin resistance does not always imply ampicillin resistance, particularly in E. faecalis, so a susceptible narrow beta-lactam may remain preferable.
Linezolid 600 mg orally or intravenously every 12 hours is a standard active option for invasive VRE; oral bioavailability permits dose-equivalent step-down when appropriate.
High-dose daptomycin 10 to 12 mg/kg intravenously every 24 hours is an off-label specialist option for VRE bloodstream and endovascular disease, often with beta-lactam synergy in persistent or endocardial infection.
Daptomycin must not be used for pneumonia, while tigecycline should not be relied upon for bloodstream or urinary infection because serum and urinary exposure are inadequate.
Use standard plus IPC-directed contact precautions, single-room or cohort placement, dedicated equipment, environmental cleaning and transfer alerts; there is no established antibiotic decolonisation regimen.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

vanA acquisition

Mobile vanA gene clusters replace the glycopeptide cell-wall target and usually confer high-level resistance to vancomycin and teicoplanin.

vanB acquisition

vanB produces variable vancomycin resistance while apparent teicoplanin susceptibility may remain, requiring expert phenotype and genotype interpretation.

Healthcare selection

Broad-spectrum antibiotics, prolonged admission, gastrointestinal surgery, devices, haematology and transplantation amplify resistant enterococci in the bowel.

Endogenous invasion

Most clinical infection follows translocation or device inoculation from the patient's colonising gastrointestinal reservoir rather than acquisition causing immediate disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Altered peptidoglycan target
Induced Van enzymes replace D-alanine-D-alanine with a low-affinity cell-wall terminus, preventing effective glycopeptide binding and cell-wall inhibition.
2
Biofilm persistence
Enterococci adhere to catheters, valves and prosthetic surfaces, forming biofilm that protects organisms from immune clearance and antibiotics.
3
Antibiotic-driven overgrowth
Suppression of competing anaerobic flora increases intestinal VRE density, making environmental shedding, transmission and bloodstream entry more likely.
4
Tolerant endovascular growth
Relative antibiotic tolerance and vegetation biofilm make enterococcal endocarditis difficult to sterilise without prolonged bactericidal combination therapy.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Gastrointestinal carriage

Rectal or faecal screening detects VRE without attributable symptoms; carriage may persist and later seed infection or spread in healthcare.

Bloodstream infectionRed flag

Fever, rigors, hypotension or organ dysfunction with VRE in blood is invasive disease, often arising from a line or gastrointestinal source.

EndocarditisRed flag

Persistent bacteraemia, murmur, valve dysfunction, emboli or prosthetic material suggests enterococcal endocarditis, which can have an indolent presentation.

Urinary isolation

Catheter-associated growth is often asymptomatic; dysuria, fever, obstruction, renal involvement or bacteraemia is required to support true urinary infection.

Abdominal and biliary diseaseRed flag

Postoperative collection, anastomotic leak, peritonitis, cholangitis or infected pancreatic necrosis can produce polymicrobial infection that includes VRE.

Red flags requiring action

Persistent blood-culture positivity beyond 48 to 72 hours on active therapy suggests retained line, undrained abdominal source, infected thrombus, endocarditis or inadequate exposure.
New murmur, heart failure, conduction abnormality, embolic lesion or prosthetic valve with VRE bacteraemia requires urgent echocardiography and endocarditis-team review.
Severe abdominal pain, peritonism, biliary obstruction or postoperative leak needs urgent imaging and source control; antibiotics alone will not sterilise ongoing contamination.
Thrombocytopenia, anaemia, neuropathy, lactic acidosis or serotonergic toxicity can limit linezolid, particularly during prolonged courses.
Muscle pain, creatine-kinase rise, renal deterioration or new respiratory symptoms during daptomycin requires toxicity review; daptomycin is inactive in pneumonia.
VanA or VanB detection in a high-risk ward, clustering of cases or inter-facility transfer should trigger immediate IPC communication and outbreak assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line blood culturesFirst stepFirst line
Why
Confirm invasive infection, evaluate sepsis and provide the clearance date that informs duration.
Interpretation and limitations
Take paired peripheral and line sets before antibiotics when safe. Repeat within 24 to 48 hours and continue until negative in bloodstream disease.
02
Species and susceptibility testing
Why
Differentiate E. faecium from E. faecalis and define ampicillin, glycopeptide, linezolid, daptomycin and other activity.
Interpretation and limitations
Use current MICs and van genotype where available. Request specialist or reference testing for linezolid or daptomycin resistance, discordance or clinical failure.
03
Echocardiography
Why
Detect vegetations, peri-valvular extension or device involvement in bacteraemia with endocarditis risk.
Interpretation and limitations
Begin with transthoracic imaging and use transoesophageal imaging for persistent bacteraemia, prosthetic valve or device, emboli, poor windows or high clinical probability.
04
Source imaging and sampling
Why
Find abdominal, biliary, urinary, thrombotic, bone, joint or prosthetic foci that require drainage or surgery.
Interpretation and limitations
Select CT, ultrasound, MRI or device assessment from symptoms. Deep aspirate or operative tissue is more meaningful than a superficial wound swab.
05
VRE carriage screening
Why
Identify colonised contacts or high-risk admissions under the local IPC and outbreak plan.
Interpretation and limitations
Rectal swab or faeces is cultured or tested molecularly. A negative result does not automatically remove a historic alert or end precautions.
06
Drug safety monitoring
Why
Prevent marrow, neurological, serotonergic or muscle toxicity during prolonged anti-VRE treatment.
Interpretation and limitations
Obtain baseline FBC, renal and liver profiles, creatine kinase and interacting medicines, then monitor according to linezolid or daptomycin exposure.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

VRE colonisation

Detection from bowel, catheter urine or superficial sites without attributable inflammation or physiology represents carriage rather than clinical infection.

Other enterococcal phenotype

Vancomycin-susceptible or intrinsically low-level-resistant Enterococcus species require different interpretation and may retain useful ampicillin or glycopeptide treatment options.

Staphylococcal line infection

Coagulase-negative staphylococci and S. aureus also cause device bacteraemia; accurate species identification determines virulence, duration and source management.

Gram-negative abdominal sepsis

Enterobacterales and anaerobes commonly coexist in gastrointestinal sources, so targeted VRE therapy cannot replace appropriate broader initial coverage.

Non-infectious fever

Drug reaction, thrombosis, malignancy and inflammatory disease can coincide with VRE carriage and should not be attributed to a screen.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01COLONISATIONDecide whether treatment is neededFirst stepVRE is reported from screening, urine, wound, drain or another clinical specimen.

1Examine for local inflammation and systemic illness, identify the specimen quality and ask whether another organism or non-infectious cause better explains the presentation.
2Do not treat a rectal screen, asymptomatic bacteriuria or colonised wound; remove unnecessary urinary or vascular devices and improve wound containment.
3Obtain blood cultures and deep source specimens before therapy when fever, sepsis, sterile-site disease or a high-risk source is present.
4Alert IPC to arrange precautions, screening and communication independently of whether antimicrobial treatment is indicated.

02BLOODSTREAMTreat invasive VREVRE is recovered from blood or another normally sterile site with compatible infection.

1Start linezolid 600 mg orally or intravenously every 12 hours or high-dose daptomycin 10 to 12 mg/kg intravenously daily according to site, susceptibility, toxicity and specialist advice.
2Use a susceptible ampicillin or amoxicillin regimen instead when the isolate remains beta-lactam susceptible and the anatomical syndrome does not require another approach.
3Repeat blood cultures to clearance, remove an implicated central line where feasible and drain abdominal, biliary or other collections promptly.
4Treat uncomplicated catheter-related disease commonly for 7 to 14 days after clearance and source control; extend for endocarditis, thrombosis, bone, joint or retained material.

03ENDOCARDITISManage endovascular infectionPersistent bacteraemia, echocardiographic lesion, prosthetic valve or clinical features indicate VRE infective endocarditis.

1Convene infection, cardiology, microbiology, cardiac surgery and pharmacy teams early because evidence is limited and cure often requires combined treatment and surgery.
2Use daptomycin 10 to 12 mg/kg intravenously daily with an active beta-lactam or fosfomycin synergy strategy, or linezolid, selected from species, MIC and patient factors.
3Repeat cultures until clear and monitor for emboli, heart failure, conduction change, abscess and valve destruction; pursue surgery according to standard endocarditis indications.
4Treat for approximately six weeks and longer when prosthetic or uncontrolled infection requires it, with regimen and duration owned by the endocarditis team.

04SITE-SPECIFICAvoid pharmacokinetic mismatchesThe VRE infection is confined to lung, urine, abdomen, skin, bone or another site with distinct drug exposure.

1Use linezolid rather than daptomycin for genuine VRE pneumonia because pulmonary surfactant inactivates daptomycin.
2For uncomplicated cystitis, use nitrofurantoin or oral fosfomycin only when the species is susceptible and there is no fever, prostate, renal or bloodstream involvement.
3Do not use tigecycline for bacteraemia or urinary infection; reserve it for selected susceptible tissue or abdominal disease when better agents are unavailable.
4Use surgery, drainage or device removal whenever anatomy protects the infection, then set duration from the controlled site and response.

05CONTAINPrevent healthcare transmissionVRE carriage or infection is detected in hospital, dialysis, care-home transfer or a high-risk clinical service.

1Use standard precautions plus IPC-directed contact precautions, side-room or cohort placement and dedicated equipment according to setting and transmission risk.
2Emphasise hand hygiene, toilet and commode cleaning, environmental decontamination and careful management of faeces, wounds, linen and devices.
3Screen contacts or staff only when IPC epidemiology indicates it and communicate carriage before transfer, procedure, readmission or shared-care attendance.
4Do not prescribe oral antibiotics, probiotics or bowel preparations to eradicate carriage; no reliable routine VRE decolonisation method exists.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Standard active option for VRE bloodstream, pulmonary, tissue and selected endovascular infection when the isolate is susceptible.

Linezolid

Give 600 mg orally or intravenously every 12 hours; use the same dose after oral conversion because bioavailability is near complete.

Monitor FBC at least weekly and more often with renal disease or prolonged treatment; review serotonergic medicines, lactic acidosis, optic or peripheral neuropathy and hypoglycaemia.

Bactericidal option for bloodstream and deep infection, particularly high-burden or persistent E. faecium disease.

High-dose daptomycin

Give 10 to 12 mg/kg intravenously every 24 hours for serious VRE bacteraemia or endovascular infection under specialist off-label governance, with renal interval adjustment.

Do not use for pneumonia; monitor baseline and at least weekly creatine kinase, renal function, muscle symptoms, statins, eosinophilic pneumonia and emerging susceptibility.

Preferred narrow beta-lactam when vancomycin resistance coexists with retained aminopenicillin susceptibility, more often in E. faecalis.

Ampicillin or amoxicillin

For a susceptible severe isolate, use ampicillin 2 g intravenously every four hours or amoxicillin 2 g intravenously every four hours, with renal adjustment and site-specific combination review.

Confirm current MIC and allergy, sodium load and renal function; endocarditis requires a synergistic specialist regimen rather than assumed monotherapy.

Narrow oral treatment for symptomatic bladder-confined infection without systemic features.

Nitrofurantoin

For susceptible uncomplicated lower UTI only, give modified-release nitrofurantoin 100 mg orally twice daily for three days in a non-pregnant woman or seven days in a man.

Do not use for pyelonephritis, prostatitis, obstruction or bacteraemia; check renal function, pregnancy near term and pulmonary, hepatic and neurological toxicity.

Alternative bladder-confined oral therapy when susceptibility and species support it.

Fosfomycin

For susceptible uncomplicated lower UTI in an adult woman, give fosfomycin trometamol 3 g orally as a single dose; male or complicated regimens require specialist advice.

Do not extrapolate to renal, prostate or bloodstream disease and do not assume E. faecium susceptibility; review sodium formulations and local laboratory testing.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Infective endocarditis

Persistent bloodstream seeding produces progressive valve destruction, systemic emboli, peri-valvular abscess, heart failure and difficult-to-eradicate prosthetic infection.

Metastatic infection

Bacteraemia can seed vertebrae, joints, vascular thrombi and other sites, prolonging pain, disability and antimicrobial duration.

Recurrent bacteraemia

Retained line, undrained abdominal disease, biofilm or ongoing bowel translocation causes relapse after apparent microbiological clearance.

Healthcare transmission

Persistent faecal carriage contaminates hands, shared equipment and the environment, producing clusters among highly vulnerable patients.

Treatment-limiting toxicity

Linezolid marrow and neurological injury or daptomycin myopathy can interrupt prolonged therapy and leave few active alternatives.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat blood cultures within 24 to 48 hours and until clearance; persistent positivity requires a renewed source, valve, thrombosis and exposure investigation.
Monitor FBC at least weekly during linezolid and more often with baseline marrow disease, renal dysfunction or courses beyond two weeks.
Check creatine kinase, renal function and muscle symptoms during daptomycin and reconsider statins or other myotoxic medicines.
Track drainage, device removal, echocardiography and focal symptoms rather than using fever or CRP alone to determine cure.
Review species, MIC and any van genotype, repeating susceptibility during persistent or recurrent infection because linezolid and daptomycin resistance can emerge.
IPC should retain an accurate alert, document screening and precautions and communicate status at discharge and future readmission without stigmatising the patient.
VRE is not routinely clinician-notifiable in England; report healthcare clusters through IPC and health-protection channels and follow current laboratory surveillance arrangements.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Vancomycin resistance is not universal resistance

Some VRE, particularly E. faecalis, remains ampicillin susceptible, allowing a narrower and often more bactericidal beta-lactam strategy.

Species predicts difficulty

Healthcare E. faecium commonly combines vancomycin and ampicillin resistance, while E. faecalis more often retains useful beta-lactam susceptibility.

Urine often misleads

Enterococci readily colonise urinary catheters, so replacing the device and assessing symptoms prevents unnecessary linezolid or daptomycin exposure.

Beta-lactam can potentiate daptomycin

For persistent high-burden infection, selected beta-lactams alter cell-surface charge and may enhance daptomycin activity despite lacking independent susceptibility.

Carriage can persist

Bowel colonisation may outlast infection treatment by months, making communication and risk-based precautions more useful than repeated eradication attempts.

11Common pitfallsFrequent interpretation and management errors.

01
Do not treat a positive rectal screen, asymptomatic catheter urine or colonised superficial wound with linezolid or daptomycin.
02
Do not assume vancomycin resistance means ampicillin resistance; inspect species and the full susceptibility profile.
03
Do not use daptomycin for pneumonia or tigecycline for bacteraemia and urinary infection.
04
Do not declare bloodstream infection cleared without repeat cultures and deliberate line, abdominal and cardiac source assessment.
05
Do not continue linezolid for weeks without blood-count, interaction, neurological and lactic-acidosis monitoring.
06
Do not attempt routine antibiotic decolonisation or remove IPC alerts after one negative screen.