Coagulase-Negative Staphylococcal Infections in the Neonate and Child: An Update

https://doi.org/10.1053/j.spid.2006.06.005Get rights and content

Coagulase-negative staphylococcus (CONS) infection is the most common bloodstream infection treated in neonatal and pediatric intensive care units and significantly impacts patient mortality and morbidity. Staphylococcus epidermidis is the most common CONS species isolated clinically and investigated for its pathogenicity and virulence. Difficulties exist in the differentiation of CONS infection from culture contamination in clinical specimens, as CONS is a common skin commensal. Most CONS isolates have the mecA gene and exhibit beta-lactam resistance. The glycopeptide antibiotics, such as vancomycin, are the mainstay in therapy, although resistance has been reported. Arbekacin, linezolid, and streptogramins are newer antibiotics being evaluated as alternatives to glycopeptides. Monoclonal and polyclonal antibodies have been developed against the cell-wall components of staphylococcus and may hold promise for immune prophylaxis and treatment of CONS infection.

Section snippets

CONS Species

Thirty-eight species of CONS have been recognized, and 13 of them are known to colonize humans (see ftp://ftp.cict.fr/pub/bacterio/). Novobiocin susceptibility is useful in differentiating CONS species into two groups. The novobiocin-resistant strains include Staphyloccocus saprophyticus and Staphyloccocus xylosus, with the former being well known to cause urinary tract infections in immune-competent women.7 Novobiocin-susceptible strains include Staphyloccocus epidermidis, Staphyloccocus

Pathogenicity and Virulence

Most research into virulence factors, specifically those involved in adhesion, aggregation, and biofilm (slime) formation, has been conducted with S. epidermidis.

Diagnosis

Establishing the diagnosis of CONS sepsis or infection can be complex, and difficulty exists in differentiating infection from contamination. CONS is a commensal and can contaminate cultures. This contamination may occur either at the time of blood sampling or during the blood culture process. Different definitions exist for the diagnosis of a true CONS sepsis. The most commonly used neonatal definitions for CONS infection involve one positive culture with clinical signs or symptoms of

Antibiotics

Antibiotics are the mainstay in the treatment of CONS infections. Penicillinase-resistant penicillins (eg, nafcillin or oxacillin) are not the drugs of choice in view of the high rates of methicillin resistance, ranging from 70 to 92 percent.45 Therefore, glycopeptides such as vancomycin are the first choice for treatment of CONS infections.46 Teicoplanin is another glycopeptide (not available in the United States) that has several advantages (it can be given intravenously or intramuscularly,

Catheter Dressing

Avoiding the use of CVCs, use of closed medication systems, and limiting access to central lines reduces the incidence of sepsis significantly.71 The value of using a disinfectant impregnated dressing of the CVC has been evaluated in a large randomized controlled trial, in which 705 neonates were randomized to (1) Povidone-iodine (10%) scrub before line insertion or (2) alcohol (70%) scrub followed by a chlorhexidine impregnated disk over the catheter insertion site. Antimicrobial dressing

Adjuvant Treatments

Several adjuvant treatments have been evaluated in neonatal sepsis in general but not specifically in CONS sepsis. Granulocyte transfusions used for treatment in neonates with sepsis and neutropenia77and granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor used to treat or prevent sepsis in neonates did not reduce the rate of mortality.78 Pentoxifylline, a xanthine derivative that inhibits the release of tumor necrosis factor-α, has been shown to reduce

Infection Control

Epidemiological investigations during outbreaks are important in delineating the source of infection and in interrupting transmission. Conventional techniques (biotyping, antibiograms, serotyping etc.) have been supplanted by molecular techniques (PCR, gel electrophoresis). Molecular epidemiological tools may be useful for recognizing patterns of transmission, identifying sources of infection, and assessing the effect of interventions.92 Using molecular techniques (pulsed-field gel

References (98)

  • A. Savey et al.

    An analysis of the microbial flora of premature neonates

    J Hosp Infect

    (1992)
  • W. Kohnen et al.

    Development of a long-lasting ventricular catheter impregnated with a combination of antibiotics

    Biomaterials

    (2003)
  • O. Raimundo et al.

    Molecular epidemiology of coagulase-negative staphylococcal bacteraemia in a newborn intensive care unit

    J Hosp Infect

    (2002)
  • C. van Pelt et al.

    Strict infection control measures do not prevent clonal spread of coagulase negative staphylococci colonizing central venous catheters in neutropenic hemato-oncologic patients

    FEMS Immunol Med Microbiol

    (2003)
  • National Nosocomial Infections Surveillance (NNIS) System Report, Data Summary from January 1992-June 2001

    Am J Infect Control

    (2001)
  • T.G. Krediet et al.

    Prevalence of molecular types and mecA gene carriage of coagulase-negative Staphylococci in a neonatal intensive care unitrelation to nosocomial septicemia

    J Clin Microbiol

    (2001)
  • B.J. Stoll et al.

    Late-onset sepsis in very low birth weight neonatesthe experience of the NICHD Neonatal Research Network

    Pediatrics

    (2002)
  • M.G. Karlowicz et al.

    Fulminant late-onset sepsis in a neonatal intensive care unit, 1988-1997, and the impact of avoiding empiric vancomycin therapy

    Pediatrics

    (2000)
  • D. Pittet et al.

    Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality

    JAMA

    (1994)
  • J.E. Gray et al.

    Coagulase-negative staphylococcal bacteremia among very low birth weight infantsrelation to admission illness severity, resource use, and outcome

    Pediatrics

    (1995)
  • F.A. Orrett et al.

    Significance of coagulase-negative staphylococci in urinary tract infections in a developing country

    Conn Med

    (1998)
  • J. Ruhe et al.

    Non- epidermidis coagulase-negative staphylococcal bacteremiaclinical predictors of true bacteremia

    Eur J Clin Microbiol Infect Dis

    (2004)
  • U. Kamath et al.

    Clinical significance of Staphylococcus warneri bacteremia

    J Clin Microbiol

    (1992)
  • R. Patel et al.

    Frequency of isolation of Staphylococcus lugdunensis among staphylococcal isolates causing endocarditisa 20-year experience

    J Clin Microbiol

    (2000)
  • J.M. Patti et al.

    MSCRAMM-mediated adherence of microorganisms to host tissues

    Annu Rev Microbiol

    (1994)
  • D. McKenney et al.

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

    Infect Immun

    (1998)
  • C. Vuong et al.

    Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system

    Cell Microbiol

    (2004)
  • H. Rohde et al.

    Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases

    Mol Microbiol

    (2005)
  • L. Xu et al.

    Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis

    Infect Immun

    (2006)
  • G.D. de Silva et al.

    The ica operon and biofilm production in coagulase-negative Staphylococci associated with carriage and disease in a neonatal intensive care unit

    J Clin Microbiol

    (2001)
  • R.D. Stout et al.

    Staphylococcal exopolysaccharides inhibit lymphocyte proliferative responses by activation of monocyte prostaglandin production

    Infect Immun

    (1992)
  • C. Klingenberg et al.

    Coagulase-negative staphylococcal sepsis in neonates. Association between antibiotic resistance, biofilm formation and the host inflammatory response

    Pediatr Infect Dis J

    (2005)
  • D.W. Scheifele et al.

    Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis

    Infect Immun

    (1987)
  • T.G. Krediet et al.

    Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma

    Pediatr Res

    (1998)
  • H.A. Lassiter et al.

    Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates

    Pediatr Infect Dis J

    (1991)
  • K. Buzas et al.

    Different staphylococcal strains elicit different levels of production of T-helper 1-inducing cytokines

    Acta Microbiol Immunol Hung

    (2004)
  • D. Isaacs

    A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units

    Arch Dis Child Fetal Neonatal Ed

    (2003)
  • S. Struthers et al.

    A comparison of two versus one blood culture in the diagnosis and treatment of coagulase-negative staphylococcus in the neonatal intensive care unit

    J Perinatol

    (2002)
  • I.R. Makhoul et al.

    PCR-based diagnosis of neonatal staphylococcal bacteremias

    J Clin Microbiol

    (2005)
  • A. Craft et al.

    Nosocomial coagulase negative staphylococcal catheter-related sepsis in preterm infantsdefinition, diagnosis, prophylaxis, and prevention

    J Perinatol

    (2001)
  • J. Langley et al.

    Sepsis in febrile neutropenic children with cancer

    Pediatr Infect Dis J

    (1988)
  • T. Celkan et al.

    Bacteremia in childhood cancer

    J Trop Pediatr

    (2002)
  • T.S. Carothers et al.

    Quantification of incidental needle and suture contamination during strabismus surgery

    Binocul Vis Strabismus Q

    (2003)
  • R.H. Latham et al.

    Urinary tract infections in young adult women caused by Staphylococcus saprophyticus

    JAMA

    (1983)
  • A. Maayan-Metzger et al.

    Clinical and laboratory impact of coagulase-negative staphylococci bacteremia in preterm infants

    Acta Paediatr

    (2000)
  • M.G. Karlowicz et al.

    Central venous catheter removal versus in situ treatment in neonates with coagulase-negative staphylococcal bacteremia

    Pediatr Infect Dis J

    (2002)
  • J. Freeman et al.

    Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units

    N Engl J Med

    (1990)
  • J. Gruskay et al.

    Neonatal Staphylococcus epidermidis meningitis with unremarkable CSF examination results

    Am J Dis Child

    (1989)
  • B.H. Eggink et al.

    Primary osteomyelitis and suppurative arthritis caused by coagulase-negative staphylococci in a preterm neonate

    Pediatr Infect Dis J

    (2003)
  • Cited by (80)

    • Antibiotic Stewardship

      2018, Infectious Disease and Pharmacology: Neonatology Questions and Controversies
    • Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m<sup>2</sup>/day for neonates?

      2016, Brazilian Journal of Infectious Diseases
      Citation Excerpt :

      However, empirical dose of vancomycin is not ideal according to inappropriate serum levels of the drug that have been reported in neonates in several studies.5,9,10,12,13 Although there have been previous descriptions of dose calculations based on nomograms and adjustments according to drug clearance and the patient's renal function,5,14–17 no study has analyzed doses that were prescribed according to body surface (m2/day) and the resulting serum vancomycin levels. We hypothesized that higher serum levels could be achieved based on doses calculated according to body surface.

    • Analysis of nosocomial Staphylococcus haemolyticus by MLST and MALDI-TOF mass spectrometry

      2016, Infection, Genetics and Evolution
      Citation Excerpt :

      The problem of hospital CoNS infections in NICUs is a very serious one and is related to immature immune responses of preterm infants and to frequent invasive procedures (Craft and Finer, 2001; Mohan et al., 2006). The main CoNS infections in NICUs include lung disease and sepsis, often associated with the use of catheters (Craft and Finer, 2001; Mohan et al., 2006). According to the microbiological monitoring carried out in NICUs of the Research Centre for Obstetrics, Gynecology and Perinatology in Moscow (RCOGP), CoNS are the most common group of microorganisms that cause infection, and Staphylococcus haemolyticus is the second most common species among CoNS after Staphylococcus epidermidis (Lubasovskaia et al., 2013).

    View all citing articles on Scopus
    View full text