What is coagulase-negative staphylococcus (CoNS) species?

What is Coagulase-Negative Staphylococcus (CoNS) Species?

Coagulase-negative staphylococci (CoNS) are a group of over 40 bacterial species that lack the ability to produce free coagulase enzyme, distinguishing them from the more virulent Staphylococcus aureus, and they normally colonize human skin and mucous membranes but have emerged as important pathogens primarily in device-related and healthcare-associated infections. 1, 2

Microbiological Definition and Species

• CoNS are differentiated from S. aureus by their inability to produce coagulase, a key laboratory test used for identification 1
• Currently over 40 recognized species exist within the CoNS group 1
• The most clinically significant species include:
  • Staphylococcus epidermidis - the most common CoNS species isolated from clinical specimens, representing 54.7% of all CoNS isolates 3
  • S. haemolyticus - the second most common, accounting for 23.4% of CoNS isolates 3
  • S. lugdunensis - a notably more virulent CoNS species that causes aggressive infections with high rates of perivalvular extension and metastatic spread 4
  • S. saprophyticus - primarily causes urinary tract infections in immunocompetent hosts 5

Normal Flora vs. Pathogen

• CoNS are normal inhabitants of healthy human skin and mucous membranes, functioning as commensals in most circumstances 1, 2
• They are most frequently encountered as contaminants of microbiological cultures, creating a major diagnostic challenge in distinguishing true infection from contamination 4
• Repeated isolation of the same CoNS species with identical antibiotic susceptibility patterns is necessary to support its role as a true pathogen rather than contamination 4
• At least two positive blood cultures, including one from a peripheral vein, are required to diagnose bacteremia 4

Clinical Significance and Infections

Device-Related Infections

• CoNS have become major pathogens primarily due to the increasing use of indwelling medical devices - their conversion from symbiont to pathogen directly reflects this medical advancement 1, 6
• They account for 60-80% of cardiovascular implantable electronic device (CIED) infections 4
• CoNS are the most common cause of prosthetic valve endocarditis, particularly early prosthetic valve endocarditis occurring within 60 days of surgery 4, 7
• They represent approximately 30% of all nosocomial bloodstream infections, with the majority being catheter-related sepsis 5
• Other important device-related infections include central nervous system shunt infections, peritoneal dialysis catheter infections, and surgical site infections 5

Native Valve Endocarditis

• While less common than prosthetic valve involvement, CoNS can cause native valve endocarditis, typically in patients with underlying valvular abnormalities such as mitral valve prolapse 4
• The clinical course is usually indolent with satisfactory response to medical or surgical therapy 4
• The exception is S. lugdunensis, which causes substantially more virulent native valve endocarditis resembling S. aureus infections 4

Other Clinical Syndromes

• Urinary tract infections (particularly S. saprophyticus in immunocompetent hosts) 5
• Endophthalmitis 5
• Surgical site infections 5
• Rarely, CoNS can cause infections in immunocompetent patients without foreign bodies 5

Pathogenic Mechanisms

Biofilm Formation

• The primary virulence mechanism of CoNS is their ability to form biofilms on foreign materials, which is the key factor in device-related infections 4, 2
• Biofilm formation occurs in two phases:
  • Phase 1: Initial attachment to polymer surfaces through physicochemical forces and specific bacterial surface adhesins (fimbria-like structures or capsular polysaccharides) 4
  • Phase 2: Bacterial accumulation into multilayered clusters embedded in extracellular slime (polysaccharide intercellular adhesin) 4, 2
• Bacteria within biofilms are significantly more resistant to antibiotics and host immune defenses 4

Adherence Properties

• CoNS adhere to plastic polymers more readily than other pathogens like E. coli or S. aureus 4
• They can bind to host extracellular matrix proteins (fibrinogen, fibronectin, collagen) that coat implanted devices through surface adhesins called MSCRAMMs (microbial surface components reacting with adherence matrix molecules) 4
• Some strains produce extracellular polysaccharide "slime" that enhances pathogenicity by protecting against phagocytosis and antimicrobial penetration 4

Virulence Factors

• CoNS lack the major virulence factors and toxins of S. aureus, making them generally less virulent 4
• Their pathogenicity relies primarily on adherence mechanisms rather than toxin production 4
• S. lugdunensis is the notable exception, expressing several virulence factors that make it more pathogenic than other CoNS species 5, 2

Antimicrobial Resistance

• Oxacillin (methicillin) resistance is prevalent among CoNS, with 55-75% of nosocomial isolates being methicillin-resistant 4, 5
• CoNS were the first organisms in which glycopeptide resistance was recognized 5
• High resistance rates exist to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid, and erythromycin 3
• Most isolates remain susceptible to vancomycin, linezolid, rifampin, and nitrofurantoin 3
• The disproportionate frequency of multidrug-resistant CoNS in CIED infections suggests healthcare environments as the primary acquisition site 4

Epidemiology and Acquisition

• CoNS infections may be acquired endogenously from the patient's own skin flora or exogenously from the hospital environment or healthcare workers' hands 4
• Clonal intra- and inter-hospital spread of S. epidermidis strains has been documented, suggesting potential need for infection control measures similar to those for MRSA 5
• The incidence of CoNS infections is increasing due to expanding use of invasive devices, rising numbers of immunocompromised patients, and changing demographics 6

Clinical Pitfalls

• The major clinical challenge is distinguishing true infection from contamination, as CoNS are common skin commensals 4, 1
• Many laboratories lack capability to identify CoNS to the species level, which is problematic since S. lugdunensis requires different clinical management than other CoNS 4
• Blood cultures may be negative in significant proportions of CoNS infections, particularly in early prosthetic valve endocarditis 7
• Biofilm-associated infections typically fail antibiotic therapy alone and require device removal for cure 6