Review
Pathogenesis of infections due to coagulasenegative staphylococci

https://doi.org/10.1016/S1473-3099(02)00438-3Get rights and content

Summary

As a group, the coagulase-negative staphylococci (CoNS) are among the most frequently isolated bacteria in the clinical microbiology laboratory and are becoming increasingly important, especially as causes of hospitalacquired infections. These bacteria are normal inhabitants of human skin and mucous membranes and, therefore, one of the major challenges of daily diagnostic work is to distinguish clinically significant CoNS from contaminant strains. This overview addresses current knowledge of the pathogenesis of infections due to CoNS and particularly focuses on virulence factors of the species Staphylococcus epidermidis. S epidermidis has been identified as a major cause of nosocomial infections, especially in patients with predisposing factors such as indwelling or implanted foreign polymer bodies. Most important in the pathogenesis of foreign-body-associated infections is the ability of these bacteria to colonise the polymer surface by the formation of a thick, multilayered biofilm. Biofilm formation takes place in two phases. The first phase involves the attachment of the bacteria to polymer surfaces that may be either unmodified or coated with host extracellular matrix proteins. In the second phase, the bacteria proliferate and accumulate into multilayered cell clusters that are embedded in an extracellular material. The bacterial factors involved in both phases of biofilm formation are discussed in this review. In addition, the most important aspects of the pathogenic potential of S saprophyticus, S lugdunensis, and S schleiferi are decribed, although, compared with S epidermidis, much less is known in these species concerning their virulence factors.

Section snippets

Coagulase-negative staphylococci as nosocomial pathogens

Data taken from the National Nosocomial Infections Surveillance System from January 1990 until May 1999 showed that coagulase-negative staphylococci (CoNS) are the most commonly reported pathogens (37·3%, compared with 12·6% for Staphylococcus aureus) isolated from bloodstream infections in intensive care unit patients.1 However, recognition of infection is hampered by the difficulty in distinguishing the infecting strain from the normal flora. CoNS have long been dismissed as culture

Spectrum of disease due to novobiocinsusceptible CoNS

Novobiocin-susceptible CoNS, particularly S epidermidis, have emerged as a major cause of nosocomial infections, and of nosocomial bacteraemia in particular. These microorganisms usually infect immunocompromised patients, such as premature babies and patients hospitalised for chemotherapy, other malignant diseases, or organ transplantation.7, 8, 9

In intravenous heroin users who develop right-sided endocarditis S epidermidis is the most frequently isolated causative organism. The drug injected

Pathogenesis of polymer-associated infection due to S epidermidis

The pathogenesis of foreign-body-associated infections with S epidermidis is characterised by the ability of this species to colonise the polymer surface by the formation of a thick, multilayered biofilm. Small numbers of bacteria from the patient's skin or mucous membranes, where these bacteria normally occur, probably contaminate the polymer during the surgical implantation of the device. Sometimes the bacteria are acquired from the hands of the surgical or clinical staff. Recently published

Extracellular enzymes and toxins

The establishment of an infection and the survival of the bacteria in the host depends on the ability to invade host tissues and to evade host defense systems, respectively. For this, staphylococci, in particular S aureus, have developed multiple mechanisms including production of several extracellular proteins and enzymes such as protein A, lipases, proteases, esterases, phospholipases, fatty-acid modifying enzymes (FAME), as well as production of haemolysins and toxins with superantigenic

Pathogenicity of S saprophyticus

In past years several potential virulence factors that may explain the pathogenic potential of this S saprophyticus have been identified and characterised. This species seems to have a greater capacity to adhere specifically to uroepithelial cells than many other staphylococcal species. Thus, a surface-exposed 160 kDa protein with haemagglutinin/adhesin properties that mediates binding to uroepithelial cells might explain the tropism for kidney colonisation of S saprophyticus.74, 75, 76 This

Diseases and virulence factors in S lugdunensis and S schleiferi

Following the description of S lugdunensis and S schleiferi in 1988, these CoNS have been reported as causative pathogens in a range of nosocomial infections. Infections include endocarditis, polymer-associated infections, osteomyelitis, septic arthritis, UTIs, and wound infections.83, 84, 85, 86, 87, 88, 89 Because multiple cases highlighted the aggressive nature of infections, particularly of endocarditis due to S lugdunensis, this species has been regarded as more pathogenic than most other

Search strategy and selection criteria

Data for this review were identified by searches of Medline, references from relevant articles and book chapters, and personal reference manager files. Reference articles were identified by a Medline search that cross-referenced the terms “coagulase-negative staphylococci”, “Staphylococcus epidermidis”, “Staphylococcus saprophyticus”, “Staphylococcus schleiferi”, and “Staphylococcus lugdunensis” with “pathogenesis” and “infection”. Only English language papers were included.

References (100)

  • S Gatermann et al.

    Identification and characterization of surface proteins from

    Staphylococcus saprophyticus. Zentralbl Bakteriol

    (1993)
  • Data summary from January 1990-May 1999, issued June 1999

    Am J Infect Control

    (1999)
  • J Huebner et al.

    Coagulase-negative staphylococci: role as pathogens

    Ann Rev Med

    (1999)
  • DJ Diekema et al.

    Survey of infections due to staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the western pacific region for the Sentry antimicrobial surveillance program, 1997–1999

    Clin Infect Dis

    (2001)
  • G Lina et al.

    Biology and pathogenicity of staphylococci other than Staphylococcus aureus and Staphylococcus epidermidis.

  • CL Pessoa-Silva et al.

    Neonatal lateonset bloodstream infection: attributable mortality, excess of length of stay, and risk factors

    Eur J Epidemiol

    (2001)
  • L Pagano et al.

    Bacteraemia in patients with hematological malignancies. Analysis of risk factors, etiological agents, and prognostic indicators

    Haematologica

    (1997)
  • D Souvenir et al.

    Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteraemia, and therapy of patients

    J Clin Microbiol

    (1998)
  • C Heilmann et al.

    Biology and pathogenicity of Staphylococcus epidermidis.

  • F Perdreau-Remington et al.

    A four-year prospective study on microbial ecology of explanted prosthetic hips in 52 patients with "aseptic" prosthetic joint loosening

    Eur J Clin Microbiol Infect Dis

    (1996)
  • F Schumacher-Perdreau et al.

    Incidence of coagulase-negative staphylococci (CNS) in fibrous capsular contracture (FCC) after augmentation mammaplasty with silicone. Abstracts of the 28th Interscience Conference of Antimicrobial Agents and Chemotherapy

    (1988)
  • B Jansen et al.

    Late onset endophthalmitis associated with intraocular lens: a case of molecularly proved

    S epidermidis aetiology. Br J Ophthalmol

    (1991)
  • NP O'Grady et al.

    Guidelines for the prevention of intravascular catheter-related infections

    MMWR Recomm Rep

    (2002)
  • G Peters et al.

    Adherence and growth of coagulase-negative staphylococci on surfaces of intravenous catheters

    J Infect Dis

    (1982)
  • G Peters et al.

    Microbial colonization of prosthetic devices. II. Scanning electron microscopy of naturally infected intravenous catheters

    Zentralbl Bakteriol Mikrobiol Hyg B

    (1981)
  • GJ Veenstra et al.

    Ultrastructural organization and regulation of a biomaterial adhesin of

    Staphylococcus epidermidis. J Bacteriol

    (1996)
  • C Heilmann et al.

    Characterization of Tn917 insertion mutants of Staphylococcus epidermidis affected in biofilm formation

    Infect Immun

    (1996)
  • C Heilmann et al.

    Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface

    Mol Microbiol

    (1997)
  • C Cucarella et al.

    Bap, a Staphylococcus aureus surface protein involved in biofilm formation

    J Bacteriol

    (2001)
  • H Shiro et al.

    Transposon mutants of Staphylococcus epidermidis deficient in elaboration of capsular polysaccharide/adhesin and slime are avirulent in a rabbit model of endocarditis

    J Infect Dis

    (1994)
  • GM Dickinson et al.

    Infections associated with indwelling devices: concepts of pathogenesis; infections associated with intravascular devices

    Antimicrob Agents Chemother

    (1989)
  • S Kochwa et al.

    Blood elements at foreign surfaces: a biochemical approach to the study of the adsorption of plasma proteins

    Ann N Y Acad Sci

    (1977)
  • CN Cottonaro et al.

    Quantitation and characterization of competitive protein binding to polymers

    Trans Am Soc Artif Intern Organs

    (1981)
  • M Herrmann et al.

    Interaction of von Willebrand Factor with

    Staphylococcus aureus. J Infect Dis

    (1997)
  • M Herrmann et al.

    Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material

    J Infect Dis

    (1988)
  • ME Rupp et al.

    Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model

    J Infect Dis

    (2001)
  • W Hell et al.

    Cloning of aas, a gene encoding a Staphylococcus saprophyticus surface protein with adhesive and autolytic properties

    Mol Microbiol

    (1998)
  • E Milohanic et al.

    The autolysin Ami contributes to the adhesion of Listeria monocytogenes toeukaryotic cells via its cell wall anchor

    Mol Microbiol

    (2001)
  • M Nilsson et al.

    A fibrinogen-binding protein of

    Staphylococcus epidermidis. Infect Immun

    (1998)
  • L Pei et al.

    Functional studies of a fibrinogen binding protein from

    Staphylococcus epidermidis. Infect Immun

    (1999)
  • L Pei et al.

    Functional study of antibodies against a fibrinogen-binding protein in Staphylococcus epidermidis adherence to polyethylene catheters

    J Infect Dis

    (2001)
  • KW McCrea et al.

    The serine-aspartate repeat (Sdr) protein family in Staphylococcus epidermidis

    Microbiology

    (2000)
  • D Mack et al.

    The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and structural analysis

    J Bacteriol

    (1996)
  • C Heilmann et al.

    Molecular basis of intercellular adhesion in the biofilm-forming

    Staphylococcus epidermidis. Mol Microbiol

    (1996)
  • ME Rupp et al.

    Characterization of the importance of polysaccharide intercellular adhesion/hemagglutinin of Staphylococcus epidermidis in the pathogenesis of biomaterial-based infection in a mouse foreign body infection model

    Infect Immun

    (1999)
  • ME Rupp et al.

    Characterization of Staphylococcus epidermidis polysaccharide intercellular adhesion/hemagglutinin in the pathogenesis of intravascular catheter-associated infection in a rat model

    Infect Immun

    (1999)
  • PD Fey et al.

    Characterization of the relationship between polysaccharide intercellular adhesin and hemagglutination in Staphylococcus aureus

    J Infect Dis

    (1999)
  • W Ziebuhr et al.

    Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates

    Infect Immun

    (1997)
  • D McKenney et al.

    The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin

    Infect Immun

    (1998)
  • SE Cramton et al.

    The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation

    Infect Immun

    (1999)
  • Cited by (684)

    • Staphylococcus lugdunensis bacteremia: clinical implications of single set positive blood cultures

      2023, Diagnostic Microbiology and Infectious Disease
      Citation Excerpt :

      Management of staphylococcal bacteremia differs significantly based on the species involved. S. aureus bacteremia is closely associated with invasive, disseminated infection and nearly always requires prolonged targeted antimicrobial therapy even if it only grows in a single blood culture [2], whereas a single positive CoNS blood culture usually represents contamination and does not require antimicrobial therapy [1,15]. However, there remain uncertainties over the management of bacteremia due to S. lugdunensis, a species which is more virulent than the other common CoNS species such as Staphylococcus epidermidis [2,6].

    View all citing articles on Scopus
    View full text