Laboratory Studies
The appropriate laboratory studies depend on the potential clinical syndrome present. Ideally, before administering empiric antibiotic therapy, obtain cultures from sites suspected to be infected, including blood, urine, peritoneal fluid, joint fluid, CSF, and/or pyogenic fluid collections in soft tissue.
Blood cultures are usually indicated in patients with possible infection who also require hospitalization. If endocarditis is suspected, obtain 3 sets of blood cultures over 1 hour or longer before administering empirical antibiotic therapy. A blood culture positive for Enterococcus species in a patient with a polymicrobial infection from an intra-abdominal source indicates the need for antimicrobial therapy, including activity against enterococci. A blood culture positive for Enterococcus species (especially if multiple cultures are positive) also warrants an evaluation for endocarditis if clinical features suggest this diagnosis. Echocardiography should be performed to help evaluate for cardiac vegetations.
Susceptibility testing is essential for all enterococcal isolates that require antimicrobial therapy.
Stool specimens, perirectal cultures that grow resistant Enterococcus, or both are the criterion standard for evaluating VRE colonization.
Multiple blood cultures that are positive for enterococci are associated with increased inpatient mortality. [30]
Imaging Studies
Echocardiography
Echocardiography should be performed when enterococcal endocarditis is suggested.
Transthoracic echocardiography is often performed as an initial screening test; if endocarditis is strongly suggested and the transthoracic echocardiography findings are negative, transesophageal echocardiography should be performed.
In patients in whom multiple blood cultures are positive for enterococci, the decision of whether to perform transesophageal echocardiography is often challenging. The NOVA scoring system was developed as a decision-making aid by assigning points to the following:
-
More than 3 positive blood cultures: 5 points
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Unknown origin of the bacteremia: 4 points
-
Underlying valvular heart disease: 2 points
-
Audible heart murmur: 1 point
A score of 4 or more had a sensitivity of 100% and a specificity of 29%. A score of less than 4 denoted a very low risk of endocarditis and would not require transesophageal echocardiography. [31]
In 2018 the DENOVA scoring system was proposed by Berge et al. [32] It added Duration of symptoms greater than or equal to 7 days, and presence of Embolization, and gave equal weight (1 point each) to all six parameters. If 3 or more points were calculated, the DENOVA score had higher specificity (83%) with equal sensitivity (100%) as the NOVA score to assist in determining the need for transesophageal echocardiography.
Abdominal CT scanning
A CT scan of the abdomen is indicated if symptoms or signs indicate a renal or gastrointestinal source of infection or if no clear focus of infection is evident elsewhere.
In elderly and/or immunocompromised patients, an intra-abdominal source of infection may manifest as minimal localizing signs or symptoms.
The scan may be ordered to include images of the pelvis in patients with suspected sigmoid or rectal disease, pelvic inflammatory disease (PID), or prostatic infection.
Ultrasonography
Ultrasonography of the kidneys, liver, and/or pelvis may be useful in determining whether an abscess is present and may be performed before CT scan or as an adjunct to CT scanning in selected cases.
Other Tests
Susceptibility testing
Blood isolates of enterococci should be tested for susceptibility. Routine testing should include penicillin or ampicillin, vancomycin, and high-level aminoglycosides. The Clinical and Laboratory Standards Institute (CLSI), formerly the National Committee for Laboratory Standards (NCCLS), recommends screening enterococci for high-level resistance to both gentamicin and streptomycin.
Urine isolates should be tested for susceptibility to ampicillin and nitrofurantoin. If resistence to both antibiotics is present, testing for susceptibility to fluoroquinolones, doxycycline, linezolid and fosfomycin can be considered.
For VRE isolates associated with infection, susceptibility testing should include a formal MIC determination for ampicillin and an assessment of beta-lactamase production in selected isolates. In addition, susceptibility testing should be requested for linezolid and may be considered for daptomycin, tigecycline, and quinupristin-dalfopristin, plus others as available, although not all of these antibiotics are FDA-approved for VRE infections. CLSI interpretive criteria are not available for non–FDA-approved indications or for certain organisms, so results must be interpreted using expert microbiological and clinical infectious-disease advice.
Procedures
Surgical/Interventional Radiology procedures
Surgical incision and drainage of skin or soft-tissue abscesses or radiology-guided aspiration of abscess material may be required in certain enterococcal infections. In many cases, removal of prosthetic devices, such as vascular catheters, shunts, and prosthetic cardiac valves or orthopedic devices, is necessary to facilitate cure of the infection. Some vascular catheters may be exchanged over a wire and antibiotic lock therapy can be attempted, but the device should be permanently removed if failure occurs.
Colonoscopy
In cases of enterococcal endocarditis of unknown source, colonoscopy should be considered in order to evaluate for occult colonic lesions that may have been associated with trans-mucosal bacteremia. [27]
Tables
Critical Illness/Sepsis |
Endovascular Infection (eg, Infectious Endocarditis) |
Central Nervous System Infection |
Bone/Joint Infection |
Serious Organ Infection (eg, Intra-abdominal or Kidney) |
Uncomplicated Skin Infections |
Bladder Infections |
|
Penicillin-Susceptible Enterococci |
Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IBW q8h Penicillin 18-30 MU daily via continuous infusion or in divided doses plus gentamicin 1 mg/kg IBW q8h Ampicillin 2 g IV q4h plus ceftriaxone 2 g IV q12h [Ampicillin plus imipenem-cilastatin] |
Ampicillin 2 g IV q4h for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-6 weeks (or streptomycin 7.5 mg/kg IBW IV or IM] Penicillin 18-30 MU daily via continuous infusion or in divided doses for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-6 weeks [or streptomycin 7.5 mg/kg IBW IV or IM] Ampicillin 2 gm IV q4h plus ceftriaxone 2 g IV q12h for 6 weeks [Ampicillin plus imipenem-cilastatin for 6 weeks] |
Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IBW q8h for 2-3 weeks Penicillin 18-30 MU daily via continuous infusion or in divided doses for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-3 weeks Ampicillin 2 g IV q4h plus ceftriaxone 2 g IV q12h for 2-3 weeks [Ampicillin plus imipenem-cilastatin for 2-3 weeks] |
Penicillin G 20-24 MU IV q24h in continuous dosing or divided q4h for 4-6 weeks Ampicillin 12 g IV q24h continuously or in 6 divided doses for 4-6 weeks (For both regimens above, synergistic aminoglycoside is optional) |
Penicillin G 20-24 MU IV q24h in continuous dosing or divided q4h Ampicillin 12 g IV q24h continuously or in 6 divided doses (For both regimens above, synergistic aminoglycoside is optional) |
Ampicillin 8 g IV daily in divided doses Penicillin G 12 MU IV divided q4-6h |
Amoxicillin (or IV ampicillin) (Other options may include oral doxycycline, linezolid, fosfomycin or chloramphenicol) |
Penicillin-Resistant Enterococci or Patient Unable to Tolerate Beta-lactams |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg/8h IV or IM or streptomycin 7.5 mg/kg IV or IM every 12 hours |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg IV or IM q8h or streptomycin 7.5 mg/kg IV or IM q12h for 6 weeks |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg IV or IM q8h or streptomycin 7.5 mg/kg IV or IM q12h for 6 weeks |
Vancomycin 15 mg/kg IV q12h for 4-6 weeks (Addition of aminoglycoside is optional) |
Vancomycin 15 mg/kg IV q12h (Addition of aminoglycoside is optional) |
Vancomycin 15 mg/kg IV q12h (Addition of aminoglycoside is optional) |
Nitrofurantoin Doxycycline Linezolid Chloramphenicol |
VRE |
Linezolid 600 mg IV or PO q12h Daptomycin 10-12 mg/kg once daily |
Linezolid 600 mg IV or PO q12h for a minimum of 6 weeks Daptomycin 10-12 mg/kg once daily for minimum of 6 weeks |
Linezolid 600 mg IV or PO q12h for 2-3 weeks |
Linezolid 600 mg IV or PO q12h for 4-6 weeks Daptomycin 6 mg/kg once daily for 4-6 weeks |
Linezolid 600 mg IV or PO q12h Daptomycin 6 mg/kg once daily |
Linezolid 600 mg IV or PO q12h Daptomycin 4-6 mg/kg once daily |
Nitrofurantoin Doxycycline Linezolid Daptomycin Chloramphenicol |
