Enterococci are gram-positive bacteria that are part of the normal human intestinal flora and can colonize the upper respiratory tract, biliary tract and vagina of otherwise healthy people. Although their virulence is relatively low, recently enterococci have emerged as significant nosocomial pathogens and are currently the 4th leading cause of hospital-acquired infections, including those associated with intravascular catheter and biliary stent implants. The frequent use of these medical devices is often associated with severe complications, including catheter-related bloodstream infections (CRBSIs) and biliary stent occlusions, because of microbial biofilm formation on the device surface.
Furthermore, other than a high level of resistance to penicillin, ampicillin and aminoglycosides, a dramatic increase in vancomycin resistance of enterococci has been recently observed in most clinical settings. Clinical strains exhibiting novel mechanisms of acquired resistance to antimicrobials are frequently isolated. In addition, enterococci have a great ability to transmit these resistance traits to other species and even to other genera. Due to their associated morbidity and mortality, enterococcal infections related to medical devices currently represent a major challenge for clinicians, especially for the management of critically ill patients, resulting in prolonged hospitalization and additional health costs.
PittetD., TararaD., WenzelR.P.Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality.JAMA1994, 271: 1598–601.
11.
RichetH., HubertB., NitembergG.Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients.J Clin Microbiol1990; 28: 2520–5.
12.
CollignonP.J.Intravascular catheter associated sepsis: a common problem. The Australian Study on Intravascular Catheter Associated Sepsis.Med J Aust1994; 161: 374–8.
13.
DonowitzL.G., WenzelR.P., HoytJ.W.High risk of hospital-acquired infection in the ICU patient.Crit Care Med1982; 10: 355–7.
14.
BrownR.B., HosmerD., ChenH.C.A comparison of infections in different ICUs within the same hospital.Crit Care Med1985; 13: 472–6.
15.
ChandrasekarP.H., KruseJ.A., MatthewsM.F.Nosocomial infection among patients in different types of intensive care units at a city hospital.Crit Care Med1986; 14: 508–10.
BaldassarriL., GelosiaA., FiscarelliE., DonelliG.Microbial colonization of implanted silicone and polyurethane catheters.J Mater Sci Mater Med1994; 5: 601–5.
18.
Donelli G, De Paoli P, Fadda G, Marone P, Nicoletti G, Varaldo PE, CVC Study Group.A multicenter study on central venous catheter-associated infections in Italy.J Chemother2001; 13 Spec No 1: 251–62.
19.
PoldermanK.H., GirbesA.R.Central venous catheter use. Part 2: infectious complications.Intensive Care Med2002; 28: 18–28.
20.
SafdarN., MakiD.G.The pathogenesis of catheter-related bloodstream infection with noncuffed short-term central venous catheters.Intensive Care Med2004; 30: 62–7.
21.
HuyckeM.M., SahmD.F., GilmoreM.S.Multiple-drug resistant enterococci: the nature of the problem and an agenda for the future.Emerg Infect Dis1998; 4: 239–49.
22.
FluitA.C., SchmitzF.J., VerhoefJ.Frequency of isolation of pathogens from bloodstream, nosocomial pneumonia, skin and soft tissue, and urinary tract infections occurring in European patients.Eur J Clin Microbiol Infect Dis2001; 20: 188–91.
23.
FridkinS.K., GaynesR.P.Antimicrobial resistance in intensive care units.Clin Chest Med1999; 20: 303–16.
24.
ShlaesD.M., LevyJ., WolinskyE.Enterococcal bacteremia without endocarditis.Arch Intern Med1981; 141: 578–81.
25.
PattersonJ.E., SweeneyA.H., SimmsM.An analysis of 110 serious enterococcal infections: Epidemiology, antibiotic susceptibility and outcome.Medicine (Baltimore)1995; 74: 191–200.
26.
CottonP.B.Critical appraisal of therapeutic endoscopy in biliary tract diseases.Annu Rev Med1990; 41: 211–22.
27.
BasoliA., FioccaF., Di RosaR., BaldassarriL., DonelliG.Biliary stent occlusion: a microbiological and scanning electron microscopy (SEM) investigation. In: Zanella ed. Advances in Abdominal Surgery.Kluwer Academic Publishers1999; 69–80.
28.
Di RosaR., BasoliA., DonelliG.A microbiological and morphological study of blocked biliary stents.Microb Ecol Health Dis1999; 11: 84–8.
29.
MagiG., CaprettiR., PaolettiC.Presence of a vanA-carrying Pheromone Response Plasmid (pBRG1) in a clinical isolate of Enterococcus faecium.Antimicrob Agents Chemother2003; 47: 1571–6.
30.
DonelliG., PaolettiC., BaldassarriL.Sex pheromone-response, clumping and slime production in enterococcal strains isolated from occluded biliary stents.J Clin Microbiol2004 (in press).
31.
HakenbeckR., CoyetteJ.Resistant penicillin-binding proteins.Cell Mol Life Sci1998; 54: 332–40.
32.
MurrayB.E.The life and times of the Enterococcus.Clin Microbial Rev1990; 3: 46–65.
33.
RybkineT., MainardiJ.L., SougakoffW., CollatzE., GutmannL.Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of β-lactam resistance.J Infect Dis1998; 178: 159–63.
34.
AmyesS.G.B.Resistance to β-lactams - The permutations.J Chemother2003; 15: 525–35.
35.
LeclercqR., DerlotE., DuvalJ.Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium.N Engl J Med1988; 319: 157–61.
BoyceJ.M.Vancomycin-resistant enterococcus.Infect Dis Clin North Am1997; 11: 367–84.
39.
ZanellaR.C., ValdetaroF., LovgrenM.First confirmed case of a vancomycin-resistant Enterococcus faecium with vanA phenotype from Brazil: isolation from a meningitis case in Sao Paulo.Microb Drug Resist1999; 5: 159–62.
40.
McCarthyK.M., Van NieropW., DuseA.Control of an outbreak of vancomycin-resistant Enterococcus faecium in an oncology ward in South Africa: effective use of limited resources.J Hosp Infect2000; 44: 294–300.
41.
Hospital Infection Control Practices Advisory Committee (HICPAC).Recommendations for preventing the spread of vancomycin-resistance.Infect Control Hosp Epidemiol1995; 16: 105–13.
42.
ArthurM., ReynoldsP.E., CourvalinP.Glycopeptide resistance in enterococci.Trends Microbiol1996; 4: 401–7.
43.
FinesM., PerichonB., ReynoldsP.E., SahmD.F., CourvalinP.VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis.Antimicrob Agents Chemother1999; 43: 2161–4.
McKessarS.J., BerryA.M., BellJ.M., TurnidgeJ.D., PatonJ.C.Genetic characterization of vanG a novel vancomycin resistance locus of Enterococcus faecalis.Antimicrob Agents Chemother2000; 44: 3224–8.
46.
PowerE.G., AbdullaY.H., TalsaniaH.G., SpiceW., AathithanS., FrenchG.L.vanA genes in vancomycin-resistant clinical isolates of Oerskovia turbata and Arcanobacterium (Corynebacterium) haemolyticum.J Antimicrob Chemother1995; 36: 595–606.
47.
LigozziM., CascioG.L., FontanaR.A vanA gene cluster in a vancomycin-resistant clinical isolate of Bacillus circulans.Antimicrob Agents Chemother1998; 42: 2055–59.
48.
MeviusD., DevrieseL., ButayeP., VandameP., VerschureM., VeldmanK.Isolation of glycopeptide resistant Streptococcus gallolyticus strains with vanA, vanB and both vanA and vanB genotypes from faecal samples of veal calves in the Netherlands.J Antimicrob Chemother1998; 42: 275–6.
49.
MalathumK., MurrayB.E.Vancomycin-resistant enterococci: recent advances in genetics epidemiology and therapeutic options.Drug Resist Updat1999; 2: 224–43.
50.
ArthurM., ReynoldsP.E., DepardieuF.Mechanisms of glycopeptide resistance in enterococci.J Infect1996; 32: 11–6.
51.
ArthurM., DepardieuF., MolinasC., ReynoldsP., CourvalinP.The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin.Gene1995; 154: 87–92.
52.
ArthurM., MolinasC., DepardieuF., CourvalinP.Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147.J Bacteriol1993; 175: 117–27.
53.
LeclercqR., CourvalinP.Resistance to glycopeptides in enterococci.Clin Infect Dis1997; 24: 545–54.
RippereK., PatelR., UhlJ.R.DNA sequence resembling vanA and vanB in the vancomycin-resistant biopesticide Bacillus popilliae.J Infect Dis1998; 178: 584–88.
57.
ArthurM., MolinasC., BuggT.D., WrightG.D., WalshC.T., CourvalinP.Evidence for in vivo incorporation of D-lactate into peptidoglycan precursors of vancomycin-resistant enterococci.Antimicrob Agents Chemother1992; 36: 867–69.
58.
SafdarN., KlugerD.M., MakiD.G.A review of risk factors for catheter-related bloodstream infection caused by percutaneously inserted, noncuffed central venous catheters: implications for preventive strategies.Medicine (Baltimore)2002; 81: 466–79.
59.
CostertonJ.W.Overview of microbial biofilms.J Indus Microbiol1995; 15: 137–40.
ReifsteckF., WeeS., WilkinsonB.J.Hydrophobicity-hydrophilicity of staphylococci.J Med Microbiol1987; 24: 65–73.
62.
BaldassarriL., ChristensenG.D., DonelliG.Is slime the virulence factor in staphylococcal biomaterial-associated infections?Microecol Ther1995; 25: 103–7.
63.
BaldassarriL., DonelliG., GelosiaA., VoglinoM.C., SimpsonA., ChristensenG.D.Purification and characterization of the staphylococcal slime-associated antigen and its occurrence among Staphylococcus epidermidis clinical isolates.Infect Immun1996; 64: 3410–5.
64.
BaldassarriL., DonelliG., GelosiaA., SimpsonA.W., ChristensenG.D.Expression of slime interferes with in vitro detection of host protein receptors of Staphylococcus epidermidis.Infect Immun1997; 65: 1522–6.
65.
AmmendoliaM.G., Di RosaR., MontanaroL., ArciolaC.R., BaldassarriL.Slime production and expression of the slime-associated antigen by staphylococcal clinical isolates.J Clin Microbiol1999; 37: 3235–8.
66.
ArciolaC.R., BaldassarriL., MontanaroL.Presence of icaA and icaD genes and slime production in a collection of staphylococcal strains from catheter-associated infections.J Clin Microbiol2001; 39: 2151–6.
67.
ArciolaC.R., CampocciaD., GamberiniS., CervellatiM., DonatiE., MontanaroL.Detection of slime production by means of an optimised Congo red agar plate test based on a colourimetric scale in Staphylococcus epidermidis clinical isolates genotyped for ica locus.Biomaterials2002; 23: 4233–9.
68.
DaneseP.N., PrattL.A., KolterR.Exopolysaccharide production is required for development of Escherichia coli K-12 biofilm architecture.J Bacteriol2000; 182: 3593–6.
69.
DonelliG., LeoneF., MazzellaP., GinnettiF., RossiA., FaddaG.Qualità dei cateteri vascolari e rischio infettivo associato.G Ital Chemioter2000; 47: 29–35.
70.
FarberB.F., KaplanM.H., ClogstonA.G.Staphylococcus epidermidis extracted slime inhibits the antimicrobial action of glycopeptide antibiotics.J Infect Dis1990; 161: 37–40.
71.
GuzmanC.A., PruzzoC., LipiraG., CallegariL.Role of adherence in pathogenesis of Enterococcus faecalis urinary tract infection and endocarditis.Infect Immun1989; 57: 1834–8.
72.
KreftB., MarreR., SchrammU., WirthR.Aggregation substance of Enterococcus faecalis mediates adhesion to cultured renal tubular cells.Infect Immun1992; 60: 25–30.
73.
ShionoA., IkeY.Isolation of Enterococcus faecalis clinical isolates that efficiently adhere to human bladder carcinoma T24 cells and inhibition of adhesion by fibronectin and trypsin treatment.Infect Immun1999; 67: 1585–92.
GuzmanC.A., PruzzoC., PlatèM., GuardatiM.C., CalegariL.Serum dependent expression of Enterococcus faecalis adhesins involved in the colonization of heart cells.Microb Pathog1991; 11: 399–409.
76.
LoweA.M., LambertP.A., SmithA.W.Cloning of an Enterococcus faecalis endocarditis antigen: homology with adhesins from some oral streptococci.Infect Immun1995; 63: 703–6.
77.
RichR.L., KreikemeyerB., OwensR.T.Ace is a collagen-binding MSCRAMM from Enterococcus faecalis.J Biol Chem1999; 274: 26939–45.
JoyanesP., PascualA., Martinez-MartinezL., HeviaA., PereaE.J.In vitro adherence of Enterococcus faecalis and Enterococcus faecium to urinary catheters.Eur J Clin Microbiol Infect Dis2000; 19: 124–27.
80.
OlmstedS.B., DunnyG.M., ErlandsenS.L., WellsC.L.Plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells.J Infect Dis1994; 170: 1549–56.
81.
Toledo-AranaA., ValleJ., SolanoC.The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation.Appl Environ Microbiol2001; 67: 4538–45.
82.
CucarellaC., SolanoC., ValleJ., AmorenaB., LasaI., PenadesJ.R.Bap, a Staphylococcus aureus surface protein involved in biofilm formation.J Bacteriol2001; 183: 2888–96.
83.
CretiR., ImperiM., BertucciniL.Survey for virulence determinants among Enterococcus faecalis isolated from different sources.J Med Microbiol2004; 53: 13–20.
84.
ChowJ.W., ThalL.A., PerriM.B.Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis.Antimicrob Agents Chemother1993; 37: 2474–77.
85.
GilmoreM.S. ed. The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance.Washington DC: American Society of Microbiology2002.
86.
MakinenP.L., ClewellD.B., AnF., MakinenK.K.Purification and substrate specificity of a strongly hydrophobic extracellular metalloendopeptidase (“gelatinase”) from Streptococcus faecalis (strain OG1–10).J Biol Chem1989; 264: 3325–34.
87.
ArchimbaudC., ShankarN., ForestierC.In vitro adhesive properties and virulence factors of Enterococcus faecalis strains.Res Microbiol2002; 153: 75–80.
88.
FoleyI., GilbertP.In-vitro studies of the activity of glycopeptide combinations against Enterococcus faecalis biofilms.J Antimicrob Chemother1997; 40: 667–72.
89.
LeungJ.W., LauG.T., SungJ.J., CostertonJ.W.Decreased bacterial adherence to silver-coated stent material: an in vitro study.Gastrointest Endosc1992; 38: 338–40.
90.
DonelliG., FrancoliniI.Efficacy of antiadhesive, antibiotic and antiseptic coatings in preventing catheter-related infections.J Chemother2001; 13: 595–606.
91.
DonelliG., FrancoliniI., PiozziA., Di RosaR., MarconiW.New polymer-antibiotic systems to inhibit bacterial biofilm formation: a suitable approach to prevent central venous catheter-associated infections.J Chemother2002; 14: 501–7.
92.
DonelliG., FrancoliniI., Di CarloV.Protocollo per la prevenzione, diagnosi e terapia delle infezioni associate a cateteri venosi centrali. Rapporti ISTISAN 02/34, 2002; iii, 33p.
93.
De GaudioA.R., Di FilippoA.Device-related infections in critically ill patients. Part I: Prevention of catheter-related bloodstream infections.J Chemother2003; 15: 419–27.
