- Author: Susan L Fraser, MD; Chief Editor: John L Brusch, MD, FACP more...
Enterococci are part of the normal intestinal flora of humans and animals. They have been long recognized as important human pathogens and are becoming increasingly so. The genus Enterococcus includes more than 17 species, although only a few cause clinical infections in humans. Since the beginning of the antibiotic era, they have posed major therapeutic challenges, including the need for synergistic combinations of antibiotics to successfully treat enterococcal infective endocarditis (IE).
Enterococcus species are facultative anaerobic organisms that can survive temperatures of 60°C for short periods and that grow in high salt concentrations. In the laboratory, enterococci are distinguished by their morphologic appearance on Gram stain and culture (gram-positive cocci that grow in chains) and their ability to (1) hydrolyze esculin in the presence of bile, (2) their growth in 6.5% sodium chloride, (3) their hydrolysis of pyrrolidonyl arylamidase and leucine aminopeptidase, and (4) their reaction with group D antiserum. Before they were assigned their own genus, they were classified as group D streptococci.
Enterococcus faecalis and Enterococcus faecium are the most prevalent species cultured from humans, accounting for more than 90% of clinical isolates. Other enterococcal species known to cause human infection include Enterococcus avium, Enterococcus gallinarum, Enterococcus casseliflavus, Enterococcus durans, Enterococcus raffinosus, and Enterococcus mundtii. E faecium is responsible for most vancomycin-resistant enterococci (VRE) infections.
Isolation of enterococci resistant to multiple antibiotics has become increasingly common in the hospital setting. According to National Nosocomial Infections Surveillance (NNIS) data from January 2003 through December 2003, more than 28% of enterococcal isolates in ICUs of the more than 300 participating hospitals were vancomycin-resistant. Clonal spread is the dominant factor in the dissemination of multidrug-resistant enterococci in North America and Europe. Virulence and pathogenicity factors have been described using molecular techniques. Several genes isolated from resistant enterococci (agg, gelE, ace, cylLLS, esp, cpd, fsrB) encode virulence factors such as the production of gelatinase and hemolysin, adherence to caco-2 and hep-2 cells, and capacity for biofilm formation.[4, 3]
Enterococci have both an intrinsic and acquired resistance to antibiotics, making them important nosocomial pathogens. Intrinsically, enterococci tolerate or resist beta-lactam antibiotics because they contain penicillin-binding proteins (PBPs); therefore, they are still able to synthesize some cell-wall components. They are intrinsically resistant to penicillinase-susceptible penicillin (low level), penicillinase-resistant penicillins, cephalosporins, nalidixic acid, aztreonam, macrolides, and low levels of clindamycin and aminoglycosides. They use already-formed folic acid, which allows them to bypass the inhibition of folate synthesis, resulting in resistance to trimethoprim-sulfamethoxazole.
Enterococci also have acquired resistance, which includes resistance to penicillin by beta-lactamases, chloramphenicol, tetracyclines, rifampin, fluoroquinolones, aminoglycosides (high levels), and vancomycin. The genes that encode intrinsic or acquired vancomycin resistance result in a peptide to which vancomycin cannot bind; therefore, cell-wall synthesis is still possible.
Unlike streptococcal species, enterococci are relatively resistant to penicillin, with minimum inhibitory concentrations (MICs) that generally range from 1-8 mcg/mL for E faecalis and 16-64 mcg/mL for E faecium. Therefore, exposure to these antibiotic agents inhibits but does not kill these species. Combining a cell wall–active agent such as ampicillin or vancomycin with an aminoglycoside may result in synergistic bactericidal activity against enterococci.
The acquisition of vancomycin resistance by enterococci has seriously affected the treatment and infection control of these organisms. VRE, particularly E faecium strains, are frequently resistant to all antibiotics that are effective treatment for vancomycin-susceptible enterococci, which leaves clinicians treating VRE infections with limited therapeutic options.
Newer antibiotics (eg, quinupristin-dalfopristin, linezolid, daptomycin, tigecycline) with activity against many VRE strains have improved this situation, but resistance to these agents has already been described. A mutation (G2576U) in the domain V of the 23S rRNA is responsible for linezolid resistance, whereas resistance to quinupristin-dalfopristin may be the result of several mechanisms: modification of enzymes, active efflux, and target modification. Resistance of E faecalis and E faecium to daptomycin, a newer cyclic lipopeptide antibiotic that acts on the bacterial cell membrane, has also been reported.
It appears that the beta-lactam antibiotics ceftaroline, ertapenem, ampicillin, cefepime, and ceftriaxone can increase the in vitro activity of daptomycin against vancomycin-resistant E faecalis and E faecium. Ceftaroline and daptomycin appeared to be the most effective combination. In a study of synergistic combinations against isolates resistant to daptomycin, a combination of daptomycin and ampicillin appeared to be the most synergistic. The unavailability of clinical synergistic data for a specific isolate limits treatment to the mainstays of therapy against resistant enterococci, linezolid and daptomycin.
Six phenotypes of vancomycin resistance, termed VanA, VanB, VanC, VanD, VanE, and VanG, have been described. The VanA and VanB phenotypes are clinically significant and mediated by 1-2 acquired transferable operons that consist of 7 genes in 2 clusters termed VANA and VANB operons. In 1988, these gene clusters first were reported in enterococcal strains. VanA is carried on a transposon Tn1546 that is almost always plasmid-mediated.
In the United States and Europe, the 3 major phenotypes include VanA, VanB, and VanD. VanA is the most common, and enterococcal isolates exhibit high-level resistance to both vancomycin and teicoplanin, while VanB isolates have variable resistance to vancomycin and remain susceptible to teicoplanin. The VanC phenotype is mediated by the chromosomal VANC1 and VANC2 genes, which are constitutively present in E gallinarum (VANC1) and E casseliflavus (VANC2). These genes confer relatively low resistance levels to vancomycin and are not transferable. To date, the VanD, VanE, and VanG phenotypes have been described in only a few strains of enterococci.
Three patients infected with vancomycin-resistant Staphylococcus aureus (VRSA) have been reported in the United States.[8, 9] The in vivo conjugative transfer potential of the vanA resistance gene from vancomycin-resistant E faecalis to methicillin-resistant S aureus(MRSA) was confirmed in the first of these cases. This poses an emerging threat to patient safety. E faecium isolates with a complex-17 lineage have also emerged in hospital and community settings in 5 continents over just the past 2 decades. This continued global spread of resistant organisms and the creation of new, highly virulent pathogens from transfer of resistance genes underscore the importance of infection control and prevention, active surveillance, and use of appropriate antibiotics.
Infections commonly caused by enterococci include urinary tract infection (UTIs), endocarditis, bacteremia, catheter-related infections, wound infections, and intra-abdominal and pelvic infections. Many infecting strains originate from the patient's intestinal flora. From here, they can spread and cause UTI, intra-abdominal infection, and surgical wound infection. Bacteremia may result with subsequent seeding of more distant sites. For example, genitourinary tract infection or instrumentation often precedes the onset of enterococcal endocarditis. Meningitis, pleural space infections, and skin and soft-tissue infections have also been reported.
Intestinal colonization with resistant enterococcal strains is more common than clinical infection. In Cleveland, VRE stool isolates outnumber clinical isolates by a factor of 10 in hospitals in which active VRE surveillance is performed. Colonized patients are not only at risk of being infected but are also a potential source for the spread of organisms to the hands of health care workers, the environment, and other patients. Antibiotic-selective pressure facilitates the spread of resistant enterococcal strains by promoting overgrowth of these strains in the intestinal tract. Enterococci can survive for long periods on environmental surfaces, contributing to their transmission. VRE have been isolated from all objects and sites in health care facilities.
For colonization development and infection with VRE, antimicrobial and nonantimicrobial risk factors have been identified. Vancomycin use is associated with VRE colonization and infection, but prior exposure is not required for colonization. Third-generation cephalosporins, aminoglycosides, aztreonam, ciprofloxacin, imipenem, clindamycin, and metronidazole have been associated with VRE colonization. Nonantimicrobial risk factors (eg, increased duration of exposure to individuals colonized with VRE and close proximity to other colonized patients) increase the likelihood of VRE exposure.
Individuals at risk for colonization include critically ill patients who have received lengthy courses of antibiotics (particularly those in long-term care facilities), solid-organ transplant recipients and patients with hematologic malignancies, and health care workers. Unfortunately, spontaneous decolonization is uncommon, and antimicrobials are unlikely to eradicate VRE colonization. Identified risk factors for VRE bacteremia include prior intestinal colonization, prior long-term antibiotic use, increased severity of illness, hematologic malignancy, bone marrow transplant, mucositis, neutropenia, indwelling urinary catheters, corticosteroid treatment, chemotherapy, and parenteral nutrition.[10, 11]
The ability of enterococci to produce biofilms both protects the organism from the body's defenses and promotes exchange of genetic material with other pathogens.
According to recent NNIS surveys, enterococci remain in the top 3 most common pathogens that cause nosocomial infections. Enterococci frequently cause UTIs, bloodstream infections, and wound infections in hospitalized patients. Nosocomial enterococcal infections typically occur in very ill debilitated patients who have been exposed to broad-spectrum antibiotics. They are the fourth most common cause of nosocomial bloodstream infections in the United States.
The increased prevalence of serious enterococcal infections has been associated with the rise of third-generation cephalosporins. These compounds have no activity against enterococci but do eradicate the aerobic and anaerobic competitive that act as suppressors of overgrowth of these pathogens in various body sites. The development of VRE also appears to be tied into the use of third-generation cephalosporins. Over the past 20 years, the incidence of multiply resistant E faecium has significantly increased; 35%-40% of enterococcal bloodstream infections involve this microorganism.
In 1989, VRE was first reported in New York City; subsequently, VRE has spread rapidly throughout the United States. From 1989-1993, the NNIS surveys reported that the percentage of enterococcal isolates exhibiting vancomycin resistance increased from 0.3% to 7.9%, with a 34-fold rise seen in ICUs. In 2003, the percentage of nosocomial enterococcal isolates exhibiting vancomycin resistance in ICU patients increased to more than 28%—an increase of 12% compared with 1998-2002.
NNIS data reveal the pooled mean for VRE species from all ICUs, non-ICU inpatient areas, and outpatient areas were 13.9%, 12%, and 4.6%, respectively, from 1998 through June 2004. VRE was initially isolated mainly in large university hospitals, but subsequent reports demonstrate the presence of significant VRE epidemics in community hospitals and chronic care facilities, whereby a single clone can easily spread. VRE is isolated almost exclusively from hospitalized (or recently hospitalized) individuals.
In contrast, Europe appears to have a large community reservoir of VRE without as rapid an increase in incidence of hospital-associated infections seen in the United States. In European countries, VanA-type VRE has been isolated from various farm animals, chicken carcasses, other meat products, and wastewater samples from sewage treatment plants. In 1994, a German community screened 100 healthy people for VRE, and 12% were found to be carriers.
In Europe, the use of avoparcin, a glycopeptide antibiotic, as a growth promoter for farm animals has been proposed to explain the epidemiology of VRE. Until banned by the European Union in 1997, avoparcin had been used in several European countries and provided a selective pressure for the emergence and spread of vancomycin-resistant genes. This hypothesis is supported by a Danish study that found VanA-type VRE in chicken stool samples from farms using avoparcin but not in samples from farms not using avoparcin. Among the Saxony-Anhalt region in Germany, the prevalence of VRE fecal colonization in healthy individuals after discontinuing avoparcin use in animal husbandry decreased from 12% to 3%, concurrent with a similar decrease in the prevalence of VRE in German poultry products.
Several outbreaks of VRE colonization and infection have been reported by hospitals in Europe and have been associated with increased mortality rates. A Korean study documented unexpectedly high levels of resistance in VRE isolates to daptomycin, linezolid, and tigecycline despite the rare use of these antibiotics in Korean hospitals.
In general, the virulence of enterococci is lower than that of organisms such as S aureus. However, enterococcal infections often occur in debilitated patients and as part of polymicrobial infections. These factors limit the ability of investigators to determine the independent contribution of enterococcal infections to mortality and morbidity. Clinical outcomes are related more to the underlying comorbidities of the patient than to the specific virulence of the infecting strain of E faecalis. Contributing factors include diabetes (36.4%), various types of cancer (30.3%), cirrhosis (6.1%), steroid therapy (19%), antecedent antibiotic treatment (60.6%), and central venous (21.2%), arterial (12.1%), and urinary catheters (63.6%).
Vancomycin-resistant bacteremia increases the length of hospital stay by an average of 2 weeks, and studies calculate an attributable mortality rate of up to 37% from these infections. Mortality rates associated with enterococcal infections may exceed 50% in critically ill patients, those with solid tumors, and some transplant patients. Bacteremia caused by VRE strains carries higher mortality rates than does bacteremia due to vancomycin-susceptible strains. Despite the availability of antimicrobial agents with greater potency against VRE, one study of 113 patients with VRE bacteremia reported that such agents did not significantly change clinical outcomes.
In general, enterococcal infections are distributed equally between the sexes.
Although UTIs are more common in healthy women than in healthy men, enterococci are an uncommon cause of uncomplicated cystitis in this setting.
In published series of enterococcal endocarditis, men often outnumber women.
Enterococcal infections are more common in elderly patients because of various associated factors that are more common in these patients. For example, urinary tract catheterization and instrumentation are more common in elderly populations. Abdominal surgery for diverticulitis or biliary tract disease is also performed more commonly in elderly persons. In a recent series, most cases of enterococcal endocarditis occurred in elderly individuals.
In neonates, enterococci occasionally cause bacteremia and meningitis. Outbreaks of enterococcal infections, including VRE infections, have been reported in neonatal ICUs, pediatric ICUs, and hematology/oncology units, but, overall, VRE infections are less common in pediatric patients than in adults.
de Perio MA, Yarnold PR, Warren J, et al. Risk factors and outcomes associated with non-Enterococcus faecalis, non-Enterococcus faecium enterococcal bacteremia. Infect Control Hosp Epidemiol. 2006 Jan. 27(1):28-33. [Medline].
Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis. 2006 Jan 1. 42 Suppl 1:S25-34. [Medline].
Deshpande LM, Fritsche TR, Moet GJ, et al. Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis. 2007 Jun. 58(2):163-70. [Medline].
Klibi N, Ben Slama K, Sáenz Y, et al. Detection of virulence factors in high-level gentamicin-resistant Enterococcus faecalis and Enterococcus faecium isolates from a Tunisian hospital. Can J Microbiol. 2007 Mar. 53(3):372-9. [Medline].
Long JK, Choueiri TK, Hall GS, Avery RK, Sekeres MA. Daptomycin-resistant Enterococcus faecium in a patient with acute myeloid leukemia. Mayo Clin Proc. 2005 Sep. 80(9):1215-6. [Medline].
Smith JR, Barber KE, Raut A, Aboutaleb M, Sakoulas G, Rybak MJ. β-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. J Antimicrob Chemother. 2015 Jun. 70 (6):1738-43. [Medline].
Hindler JA, Wong-Beringer A, Charlton CL, Miller SA, Kelesidis T, Carvalho M, et al. In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci. Antimicrob Agents Chemother. 2015 Jul. 59 (7):4279-88. [Medline].
Centers for Disease Control and Prevention (CDC). Vancomycin-resistant Staphylococcus aureus--New York, 2004. MMWR Morb Mortal Wkly Rep. 2004 Apr 23. 53(15):322-3. [Medline].
Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med. 2003 Apr 3. 348(14):1342-7. [Medline].
Sakka V, Tsiodras S, Galani L, e al. Risk-factors and predictors of mortality in patients colonised with vancomycin-resistant enterococci. Clin Microbiol Infect. 2008 Jan. 14(1):14-21. [Medline].
Schmidt-Hieber M, Blau IW, Schwartz S, et al. Intensified strategies to control vancomycin-resistant enterococci in immunocompromised patients. Int J Hematol. 2007 Aug. 86(2):158-62. [Medline].
Anderson AC, Jonas D, Huber I, Karygianni L, Wölber J, Hellwig E, et al. Enterococcus faecalis from Food, Clinical Specimens, and Oral Sites: Prevalence of Virulence Factors in Association with Biofilm Formation. Front Microbiol. 2015. 6:1534. [Medline].
Brusch JL. Microbiology of infective endocarditis and clinical correlates: Gram-positive organisms. Brusch JL, ed. Infective Endocarditis: Management in the Era of Intravascular Devices. Informa Healthcare; 2007.
Qin X, Singh KV, Weinstock GM, Murray BE. Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect Immun. 2000 May. 68(5):2579-86. [Medline]. [Full Text].
Lee do K, Kim Y, Park KS, et al. Antimicrobial activity of mupirocin, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline against vancomycin-resistant enterococci (VRE) from clinical isolates in Korea (1998 and 2005). J Biochem Mol Biol. 2007 Nov 30. 40(6):881-7. [Medline].
Ceci M, Delpech G, Sparo M, Mezzina V, Sánchez Bruni S, Baldaccini B. Clinical and microbiological features of bacteremia caused by Enterococcus faecalis. J Infect Dev Ctries. 2015 Nov 30. 9 (11):1195-203. [Medline].
DiazGranados CA, Zimmer SM, Klein M, et al. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis. 2005 Aug 1. 41(3):327-33. [Medline].
Erlandson KM, Sun J, Iwen PC, et al. Impact of the more-potent antibiotics quinupristin-dalfopristin and linezolid on outcome measure of patients with vancomycin-resistant Enterococcus bacteremia. Clin Infect Dis. 2008 Jan 1. 46(1):30-6. [Medline].
Butler KM. Enterococcal infection in children. Semin Pediatr Infect Dis. 2006 Jul. 17(3):128-39. [Medline].
Stevens MP, Edmond MB. Endocarditis due to vancomycin-resistant enterococci: case report and review of the literature. Clin Infect Dis. 2005 Oct 15. 41(8):1134-42. [Medline].
McDonald JR, Olaison L, Anderson DJ, et al. Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database. Am J Med. 2005 Jul. 118(7):759-66. [Medline].
Chatterjee I, Iredell JR, Woods M, et al. The implications of enterococci for the intensive care unit. Crit Care Resusc. 2007 Mar. 9(1):69-75. [Medline].
Berk SL, Verghese A, Holtsclaw SA, Smith JK. Enterococcal pneumonia. Occurrence in patients receiving broad-spectrum antibiotic regimens and enteral feeding. Am J Med. 1983 Jan. 74(1):153-4. [Medline].
Claeys KC, Zasowski EJ, Lagnf AM, Rybak MJ. Comparison of outcomes between patients with single versus multiple positive blood cultures for Enterococcus: Infection versus illusion?. Am J Infect Control. 2016 Jan 1. 44 (1):47-9. [Medline].
Bouza E, Kestler M, Beca T, Mariscal G, Rodríguez-Créixems M, Bermejo J, et al. The NOVA score: a proposal to reduce the need for transesophageal echocardiography in patients with enterococcal bacteremia. Clin Infect Dis. 2015 Feb 15. 60 (4):528-35. [Medline].
Fernández-Hidalgo N, Almirante B, Gavaldà J, Gurgui M, Peña C, de Alarcón A, et al. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis. Clin Infect Dis. 2013 May. 56(9):1261-8. [Medline].
Gavaldà J, Len O, Miró JM, Muñoz P, Montejo M, Alarcón A, et al. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007 Apr 17. 146(8):574-9. [Medline].
Smith JR, Barber KE, Raut A, Aboutaleb M, Sakoulas G, Rybak MJ. β-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. J Antimicrob Chemother. 2015. 70 (6):1738-43. [Medline].
Hindler JA, Wong-Beringer A, Charlton CL, Miller SA, Kelesidis T, Carvalho M, et al. In vitro activity of daptomycin in combination with β-lactams, gentamicin, rifampin, and tigecycline against daptomycin-nonsusceptible enterococci. Antimicrob Agents Chemother. 2015 Jul. 59 (7):4279-88. [Medline].
Senneville E, Caillon J, Calvet B, Jehl F. Towards a definition of daptomycin optimal dose: Lessons learned from experimental and clinical data. Int J Antimicrob Agents. 2016 Jan. 47 (1):12-9. [Medline].
Ramaswamy DP, Amodio-Groton M, Scholand SJ. Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary tract infections: a short case series. BMC Urol. 2013 Jul 16. 13(1):33. [Medline]. [Full Text].
Gavaldà J, Len O, Miró JM, et al. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007 Apr 17. 146(8):574-9. [Medline].
Cunha BA. Antimicrobial therapy of multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus. Med Clin North Am. 2006 Nov. 90(6):1165-82. [Medline].
Smith PF, Booker BM, Ogundele AB, et al. Comparative in vitro activities of daptomycin, linezolid, and quinupristin/dalfopristin against Gram-positive bacterial isolates from a large cancer center. Diagn Microbiol Infect Dis. 2005 Jul. 52(3):255-9. [Medline].
Plosker GL, Figgitt DP. Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections. Pharmacoeconomics. 2005. 23(9):945-64. [Medline].
Velissariou IM. Linezolid in children: recent patents and advances. Recent Patents Anti-Infect Drug Disc. 2007 Jan. 2(1):73-7. [Medline].
Kainer MA, Devasia RA, Jones TF, et al. Response to emerging infection leading to outbreak of linezolid-resistant enterococci. Emerg Infect Dis. 2007 Jul. 13(7):1024-30. [Medline].
Pogue JM, Paterson DL, Pasculle AW, et al. Determination of risk factors associated with isolation of linezolid-resistant strains of vancomycin-resistant Enterococcus. Infect Control Hosp Epidemiol. 2007 Dec. 28(12):1382-8. [Medline].
Poutsiaka DD, Skiffington S, Miller KB, et al. Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients. J Infect. 2007 Jun. 54(6):567-71. [Medline].
Britt NS, Potter EM, Patel N, Steed ME. Comparison of the Effectiveness and Safety of Linezolid and Daptomycin in Vancomycin-Resistant Enterococcal Bloodstream Infection: A National Cohort Study of Veterans Affairs Patients. Clin Infect Dis. 2015 Sep 15. 61 (6):871-8. [Medline].
Arias CA, Panesso D, McGrath DM, Qin X, Mojica MF, Miller C, et al. Genetic basis for in vivo daptomycin resistance in enterococci. N Engl J Med. 2011 Sep 8. 365(10):892-900. [Medline].
Vouillamoz J, Moreillon P, Giddey M, et al. Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci. J Antimicrob Chemother. 2006 Dec. 58(6):1208-14. [Medline].
Carugati M, Bayer AS, Miró JM, Park LP, Guimarães AC, Skoutelis A, et al. High-dose daptomycin therapy for left-sided infective endocarditis: a prospective study from the international collaboration on endocarditis. Antimicrob Agents Chemother. 2013 Dec. 57(12):6213-22. [Medline]. [Full Text].
Draghi DC, Benton BM, Krause KM, Thornsberry C, Pillar C, Sahm DF. Comparative surveillance study of telavancin activity against recently collected gram-positive clinical isolates from across the United States. Antimicrob Agents Chemother. 2008 Jul. 52(7):2383-8. [Medline]. [Full Text].
Kosowska-Shick K, Clark C, Pankuch GA, McGhee P, Dewasse B, Beachel L. Activity of telavancin against staphylococci and enterococci determined by MIC and resistance selection studies. Antimicrob Agents Chemother. 2009 Oct. 53(10):4217-24. [Medline]. [Full Text].
Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS, Porwal A, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014 Jun 5. 370(23):2180-90. [Medline].
Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. 2013 Feb 13. 309(6):559-69. [Medline]. [Full Text].
Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014 Jun 5. [Medline].
Manley KJ, Fraenkel MB, Mayall BC, et al. Probiotic treatment of vancomycin-resistant enterococci: a randomised controlled trial. Med J Aust. 2007 May 7. 186(9):454-7. [Medline].
[Guideline] Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007 Oct 9. 116(15):1736-54. [Medline].
[Guideline] Strausbaugh LJ, Siegel JD, Weinstein RA. Preventing transmission of multidrug-resistant bacteria in health care settings: a tale of 2 guidelines. Clin Infect Dis. 2006 Mar 15. 42(6):828-35. [Medline].
Singh N, Léger MM, Campbell J, et al. Control of vancomycin-resistant enterococci in the neonatal intensive care unit. Infect Control Hosp Epidemiol. 2005 Jul. 26(7):646-9. [Medline].
Huskins WC, Huckabee CM, O'Grady NP, et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med. 2011 Apr 14. 364(15):1407-18. [Medline].
Guglielmo BJ, Dudas V, Maewal I, et al. Impact of a series of interventions in vancomycin prescribing on use and prevalence of vancomycin-resistant enterococci. Jt Comm J Qual Patient Saf. 2005 Aug. 31(8):469-75. [Medline].
de Bruin MA, Riley LW. Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review. BMC Infect Dis. 2007 Apr 10. 7:24. [Medline].
Drees M, Snydman DR, Schmid CH, et al. Prior environmental contamination increases the risk of acquisition of vancomycin-resistant enterococci. Clin Infect Dis. 2008 Mar 1. 46(5):678-85. [Medline].
Eckstein BC, Adams DA, Eckstein EC, et al. Reduction of Clostridium Difficile and vancomycin-resistant Enterococcus contamination of environmental surfaces after an intervention to improve cleaning methods. BMC Infect Dis. 2007 Jun 21. 7:61. [Medline].
Vernon MO, Hayden MK, Trick WE, et al. Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med. 2006 Feb 13. 166(3):306-12. [Medline].
Fridkin SK, Edwards JR, Courval JM, et al. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units. Ann Intern Med. 2001 Aug 7. 135(3):175-83. [Medline].
US Food and Drug Administration. FDA Drug Safety Communication: Serious CNS reactions possible when linezolid (Zyvox®) is given to patients taking certain psychiatric medications. Available at http://www.fda.gov/Drugs/DrugSafety/ucm265305.htm. Accessed: July 27, 2011.
Weber SG, Huang SS, Oriola S, et al. Legislative mandates for use of active surveillance cultures to screen for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: Position statement from the Joint SHEA and APIC Task Force. Am J Infect Control. 2007 Mar. 35(2):73-85. [Medline].
Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005 Jun 14. 111(23):e394-434. [Medline].
Beezhold DW, Slaughter S, Hayden MK, et al. Skin colonization with vancomycin-resistant enterococci among hospitalized patients with bacteremia. Clin Infect Dis. 1997 Apr. 24(4):704-6. [Medline].
Bisno AL, Dismukes WE, Durack DT, et al. Antimicrobial treatment of infective endocarditis due to viridans streptococci, enterococci, and staphylococci. JAMA. 1989 Mar 10. 261(10):1471-7. [Medline].
Boyce JM, Opal SM, Chow JW, et al. Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol. 1994 May. 32(5):1148-53. [Medline].
Bradley SJ, Wilson AL, Allen MC, et al. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage. J Antimicrob Chemother. 1999 Feb. 43(2):261-6. [Medline].
Carmeli Y, Samore MH, Huskins C. The association between antecedent vancomycin treatment and hospital-acquired vancomycin-resistant enterococci: a meta-analysis. Arch Intern Med. 1999 Nov 8. 159(20):2461-8. [Medline].
Centers for Disease Control and Prevention. Preventing the Spread of Vancomycin Resistance--A Report from the Hospital Infection Control Practices Advisory Committee prepared by the Subcommittee on Prevention and Control of Antimicrobial-Resistant Microorganisms in Hospitals. Fed Regist. 1994 May 17. 59(94):25758-63. [Medline].
Chow JW, Kuritza A, Shlaes DM, et al. Clonal spread of vancomycin-resistant Enterococcus faecium between patients in three hospitals in two states. J Clin Microbiol. 1993 Jun. 31(6):1609-11. [Medline].
Cooper GS, Shlaes DM, Jacobs MR. The role of Enterococcus in intraabdominal infections: case control analysis. Infect Dis Clin Practice. 1993. 2:332-9.
Cunha B. Antibiotic Essentials. 9th ed. Sudbury, MA: Jones & Bartlett; 2010.
Cunha BA, Mickail N, Eisenstein L. E. faecalis vancomycin-sensitive enterococcal bacteremia unresponsive to a vancomycin tolerant strain successfully treated with high-dose daptomycin. Heart Lung. 2007 Nov-Dec. 36(6):456-61. [Medline].
DeLisle S, Perl TM. Vancomycin-resistant enterococci: a road map on how to prevent the emergence and transmission of antimicrobial resistance. Chest. 2003 May. 123(5 Suppl):504S-18S. [Medline].
Donskey CJ, Chowdhry TK, Hecker MT, et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med. 2000 Dec 28. 343(26):1925-32. [Medline].
Dougherty SH. Role of enterococcus in intraabdominal sepsis. Am J Surg. 1984 Sep. 148(3):308-12. [Medline].
Edmond MB, Ober JF, Weinbaum DL, et al. Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection. Clin Infect Dis. 1995 May. 20(5):1126-33. [Medline].
Farr BM. What to think if the results of the National Institutes of Health randomized trial of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus control measures are negative (and other advice to young epidemiologists): a review and an au revoir. Infect Control Hosp Epidemiol. 2006 Oct. 27(10):1096-106. [Medline].
Gonzales RD, Schreckenberger PC, Graham MB, et al. Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. Lancet. 2001 Apr 14. 357(9263):1179. [Medline].
Goossens H. Spread of vancomycin-resistant enterococci: differences between the United States and Europe. Infect Control Hosp Epidemiol. 1998 Aug. 19(8):546-51. [Medline].
Green M, Shlaes JH, Barbadora K, et al. Bacteremia due to vancomycin-dependent Enterococcus faecium. Clin Infect Dis. 1995 Mar. 20(3):712-4. [Medline].
Greer ND. Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics. Proc (Bayl Univ Med Cent). 2006 Apr. 19(2):155-61. [Medline].
Gullberg RM, Homann SR, Phair JP. Enterococcal bacteremia: analysis of 75 episodes. Rev Infect Dis. 1989 Jan-Feb. 11(1):74-85. [Medline].
Hoge CW, Adams J, Buchanan B, et al. Enterococcal bacteremia: to treat or not to treat, a reappraisal. Rev Infect Dis. 1991 Jul-Aug. 13(4):600-5. [Medline].
Kaye D. Enterococci. Biologic and epidemiologic characteristics and in vitro susceptibility. Arch Intern Med. 1982 Oct 25. 142(11):2006-9. [Medline].
Kirkpatrick BD, Harrington SM, Smith D, et al. An outbreak of vancomycin-dependent Enterococcus faecium in a bone marrow transplant unit. Clin Infect Dis. 1999 Nov. 29(5):1268-73. [Medline].
Landman D, Quale JM. Management of infections due to resistant enterococci: a review of therapeutic options. J Antimicrob Chemother. 1997 Aug. 40(2):161-70. [Medline].
Lautenbach E, Bilker WB, Brennan PJ. Enterococcal bacteremia: risk factors for vancomycin resistance and predictors of mortality. Infect Control Hosp Epidemiol. 1999 May. 20(5):318-23. [Medline].
Livornese LL Jr, Dias S, Samel C, et al. Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med. 1992 Jul 15. 117(2):112-6. [Medline].
Low DE, Keller N, Barth A, et al. Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis. 2001 May 15. 32 Suppl 2:S133-45. [Medline].
Lucas GM, Lechtzin N, Puryear DW, et al. Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes. Clin Infect Dis. 1998 May. 26(5):1127-33. [Medline].
Maki DG, Agger WA. Enterococcal bacteremia: clinical features, the risk of endocarditis, and management. Medicine (Baltimore). 1988 Jul. 67(4):248-69. [Medline].
Marothi YA, Agnihotri H, Dubey D. Enterococcal resistance--an overview. Indian J Med Microbiol. 2005 Oct. 23(4):214-9. [Medline].
Martone WJ. Spread of vancomycin-resistant enterococci: why did it happen in the United States?. Infect Control Hosp Epidemiol. 1998 Aug. 19(8):539-45. [Medline].
Megran DW. Enterococcal endocarditis. Clin Infect Dis. 1992 Jul. 15(1):63-71. [Medline].
Moellering RC Jr. Emergence of Enterococcus as a significant pathogen. Clin Infect Dis. 1992 Jun. 14(6):1173-6. [Medline].
Montecalvo MA, Jarvis WR, Uman J, et al. Infection-control measures reduce transmission of vancomycin-resistant enterococci in an endemic setting. Ann Intern Med. 1999 Aug 17. 131(4):269-72. [Medline].
Montecalvo MA, Shay DK, Gedris C, et al. A semiquantitative analysis of the fecal flora of patients with vancomycin-resistant enterococci: colonized patients pose an infection control risk. Clin Infect Dis. 1997 Oct. 25(4):929-30. [Medline].
Morris JG Jr, Shay DK, Hebden JN, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center. Ann Intern Med. 1995 Aug 15. 123(4):250-9. [Medline].
Murray BE. Diversity among multidrug-resistant enterococci. Emerg Infect Dis. 1998 Jan-Mar. 4(1):37-47. [Medline].
Murray BE. Vancomycin-resistant enterococci. Am J Med. 1997 Mar. 102(3):284-93. [Medline].
Murray BE, Singh KV, Markowitz SM, et al. Evidence for clonal spread of a single strain of beta-lactamase- producing Enterococcus (Streptococcus) faecalis to six hospitals in five states. J Infect Dis. 1991 Apr. 163(4):780-5. [Medline].
National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004 Dec. 32(8):470-85. [Medline].
Norris AH, Reilly JP, Edelstein PH, et al. Chloramphenicol for the treatment of vancomycin-resistant enterococcal infections. Clin Infect Dis. 1995 May. 20(5):1137-44. [Medline].
Ostrowsky BE, Trick WE, Sohn AH, et al. Control of vancomycin-resistant enterococcus in health care facilities in a region. N Engl J Med. 2001 May 10. 344(19):1427-33. [Medline].
Ostrowsky BE, Venkataraman L, D'Agata EM, et al. Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period. Arch Intern Med. 1999 Jul 12. 159(13):1467-72. [Medline].
Patterson JE, Sweeney AH, Simms M, et al. An analysis of 110 serious enterococcal infections. Epidemiology, antibiotic susceptibility, and outcome. Medicine (Baltimore). 1995 Jul. 74(4):191-200. [Medline].
Poulakou G, Giamarellou H. Oritavancin: a new promising agent in the treatment of infections due to Gram-positive pathogens. Expert Opin Investig Drugs. 2008 Feb. 17(2):225-43. [Medline].
Rafferty ME, McCormick MI, Bopp LH, et al. Vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile cytotoxin assay. Infect Control Hosp Epidemiol. 1997 May. 18(5):342-4. [Medline].
Rice LB. Emergence of vancomycin-resistant enterococci. Emerg Infect Dis. 2001 Mar-Apr. 7(2):183-7. [Medline].
Roghmann MC, McCarter RJ Jr, Brewrink J, et al. Clostridium difficile infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in VRE-colonized patients with acute leukemia. Clin Infect Dis. 1997 Nov. 25(5):1056-9. [Medline].
Shay DK, Maloney SA, Montecalvo M, et al. Epidemiology and mortality risk of vancomycin-resistant enterococcal bloodstream infections. J Infect Dis. 1995 Oct. 172(4):993-1000. [Medline].
Shlaes DM, Levy J, Wolinsky E. Enterococcal bacteremia without endocarditis. Arch Intern Med. 1981 Apr. 141(5):578-81. [Medline].
Siegel JD, Rhinehart E, Jackson M, Chiarello L, HICPAC. Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings 2007. CDC. June 2007. Available at http://www.cdc.gov/ncidod/dhap/pdf/isolation2007.pdf.
Siegel JD, Rhinehart E, Jackson M, Chiarello L, HICPAC. Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006. CDC. 2006. Available at http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf.
Suppola JP, Kuikka A, Vaara M, et al. Comparison of risk factors and outcome in patients with Enterococcus faecalis vs Enterococcus faecium bacteraemia. Scand J Infect Dis. 1998. 30(2):153-7. [Medline].
Suppola JP, Volin L, Valtonen VV, et al. Overgrowth of Enterococcus faecium in the feces of patients with hematologic malignancies. Clin Infect Dis. 1996 Oct. 23(4):694-7. [Medline].
Trick WE, Kuehnert MJ, Quirk SB, et al. Regional dissemination of vancomycin-resistant enterococci resulting from interfacility transfer of colonized patients. J Infect Dis. 1999 Aug. 180(2):391-6. [Medline].
Whiteside M, Moore J, Ratzan K. An investigation of enterococcal bacteremia. Am J Infect Control. 1983 Aug. 11(4):125-9. [Medline].
Willems RJ, Top J, van Santen M, Robinson DA, Coque TM, Baquero F, et al. Global spread of vancomycin-resistant Enterococcus faecium from distinct nosocomial genetic complex. Emerg Infect Dis. 2005 Jun. 11(6):821-8. [Medline].
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 1. 39(3):309-17. [Medline].
Zeana C, Kubin CJ, Della-Latta P, et al. Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis. 2001 Aug 15. 33(4):477-82. [Medline].
Zirakzadeh A, Patel R. Vancomycin-resistant enterococci: colonization, infection, detection, and treatment. Mayo Clin Proc. 2006 Apr. 81(4):529-36. [Medline].
Zuckerman RA, Steele L, Venezia RA, et al. Undetected vancomycin-resistant Enterococcus in surgical intensive care unit patients. Infect Control Hosp Epidemiol. 1999 Oct. 20(10):685-6. [Medline].