Coagulase-Negative Staphylococcal Infections

doi:10.1016/j.idc.2008.10.001

Infectious Disease Clinics of North America

Volume 23, Issue 1, March 2009, Pages 73-98

https://doi.org/10.1016/j.idc.2008.10.001 Get rights and content

Coagulase-negative staphylococci (CNS) are differentiated from the closely related but more virulent Staphylococcus aureus by their inability to produce free coagulase. Currently, there are over 40 recognized species of CNS. These organisms typically reside on healthy human skin and mucus membranes, rarely cause disease, and are most frequently encountered by clinicians as contaminants of microbiological cultures. However, CNS have been increasingly recognized to cause clinically significant infections. The conversion of the CNS from symbiont to human pathogen has been a direct reflection of the use of indwelling medical devices. This article deals with the clinical syndromes, epidemiology, prevention, and management of infections caused by this unique group of organisms.

Section snippets

Clinical syndromes and epidemiology

The CNS, especially S epidermidis, are rarely implicated as the cause of infections of natural tissue.⁹ They are found ubiquitously residing on human skin with healthy adults harboring 10 to 24 different strains of S epidermidis.¹⁰ The number of CNS on human skin varies from 10 to 10⁵ colony-forming units (CFU)/cm² on healthy adults in the community.¹¹ Their pathogenic potential lies in their ability to colonize and proliferate on biomaterials.¹² Every type of implanted biomaterial approved for

Intravascular catheter infections

CNS are the most common cause of nosocomial bloodstream infection, responsible for 30% to 40% of these infections.¹⁷ Most CNS bloodstream infections are the result of infections of intravascular catheters. Approximately 180 million peripheral intravascular catheters and 7 million central venous catheters (CVC) are used in the United States yearly.¹⁸ Because of their transient nature (<72 hours usage) and placement sites (generally forearm or hand veins), peripheral intravascular catheters are

Vascular graft infection

Prosthetic vascular graft infection incidence ranges from 1% to 6%, dependent on the graft location.⁴¹ Infrainguinal grafts deriving from the groin have the highest rates of infection.² The CNS are the most common cause of these infections, which may occur within the first 30 days of surgery, but are more common months or years after implantation.³ The type of material used in the graft does not appear to affect infection rates. Mortality rates of 17% and morbidity rates of 41% (usually

Endocarditis

Prosthetic valve endocarditis (PVE), although uncommon, is frequently caused by CNS. Those diagnosed with PVE caused by CNS (usually S epidermidis) comprise 15% to 40% of PVE cases.3, 42, 43 Diagnosis is usually made by repeated positive blood cultures and echocardiograpy.2, 3 The infection is usually health care related (because of inoculation at the time of surgery) and manifests within 12 months of valve placement. These isolates are likely to be methicillin resistant because of their health

Cardiac devices

Cardiac pacemaker infection occurs with an incidence of 0.13% to 19.9% and a mortality of 27% to 66%.⁵¹ CNS (predominantly S epidermidis) account for at least 25% of these infections and may occur via inoculation at the time of device placement or by hematogenous seeding from another site.2, 3 One quarter of these infections occur within 1 to 2 months of insertion of the device. Clinically, patients present with inflammation at the pacer pocket site, bacteremia, or evidence of right-sided

Prosthetic joint infections

CNS are one of the most common causes of infection of prosthetic orthopedic devices.54, 55 These organisms are generally inoculated at the time of the arthroplasty and, owing to their relatively avirulent nature, may be quite indolent in their clinical presentation.⁵⁶ CNS prosthetic joint infections are usually caused by S epidermidis with a few cases caused by S lugdunensis or other CNS species.3, 57 Risk factors include previous joint surgery, duration of surgery, another infection at the

Central nervous system shunt infections

Although previously published infection rates were much higher, more recently examined series of patients indicate rates of infection of cerebrospinal fluid shunts of approximately 5%.⁶⁰ CNS are the predominant pathogen causing more than one half of these infections.61, 62 The risk of infection increases with the presence of abnormalities of the scalp at the time of shunt placement, a patient's age of younger than 6 months, reinsertion of shunt following previous infection, lack of experience

Surgical site infections

Further information regarding staphylococcal surgical site infections can be found in the section of this issue authored by Jhung and Jernigan. Surgical site infections caused by CNS occur frequently and are second only to S aureus as an etiologic agent.³ The CNS are more often cultured from superficial incisional wounds than from deeper incisional wounds and they are more likely to cause infections in “clean” procedures rather than those performed in contaminated sites (bowel, genitourinary,

Infections involving other prosthetic devices

Other implanted materials and devices that may become infected by the CNS include intraocular lenses, breast implants, and genitourinary prostheses, as well as virtually any other surgically inserted appliance.5, 66 As the list of such items in use in today's health care environment grows, it can be expected that infections caused by the CNS will also continue to increase in number.

Coagulase-negative staphylococcal infections in neonates

Neonates are a particularly high-risk population for infections caused by CNS, as CNS are currently responsible for 31% of all nosocomial infections in neonatal intensive care units in the United States and 73% of all bacteremias in this setting.⁶⁷ In addition, the number of reported cases of infection caused by CNS in neonatal ICUs continues to increase each year.⁶⁸ This is in part because of the increase in the number of preterm infants requiring the use of umbilical and central venous

Staphylococcus Saprophyticus

Besides S epidermidis, there are several other species of CNS that should be specifically discussed because of their documented pathogenic potential. The first of these, S saprophyticus, is a frequent cause of urinary tract infection (UTI) in young (18 to 35 years), sexually active women.73, 74, 75 It is a member of the normal rectal or urogenital flora of 10% of females and is the second leading cause (behind Escherichia coli) of acute UTI in this population.75, 76, 77S saprophyticus possesses

Pathogenesis and virulence traits

The virulence factors associated with the CNS are listed in Table 1. The single most important of these is the ability to produce a highly structured, tenacious biofilm on the surface of indwelling medical devices.¹⁵ Biofilm formation is thought to occur in three distinct steps. First, the cells bind to the surface of the device in a reversible manner as a result of nonspecific forces such as polarity and hydrophobicity. Next, more specific adherence occurs as a result of the production of

Clinical microbiology and molecular typing

The CNS were originally divided on the basis of colony morphology and biochemical tests by Baird-Parker in the 1960s.¹⁰² In the 1970s, Kloos and Schleifer,¹⁰³ developed a method for identifying CNS to the species level involving an array of morphologic descriptions, biochemical testing, physiologic testing, susceptibility testing results, and cell wall characterization. These have been adapted and modified to produce rapid identification kits and automated systems that differentiate the over 40

Prevention of coagulase-negative staphylococcal infection

Because the infections presented by the CNS tend to be difficult to eradicate, an emphasis is placed on preventing both the exposure of the device to the pathogen as well as hindering colonization if exposure does occur. The first and foremost means for accomplishing these goals is strict adherence to good infection control practices. It has been estimated that 6% to 32% of all nosocomial infections could be prevented through improved application of infection control procedures.²⁴ More

Prevention of intravascular catheter coagulase-negative staphylococcal infections

The singular most critical factor in prevention of infections related to indwelling vascular devices is standardization of aseptic care. The first step involves careful site selection. The density of the skin flora at the insertion site plays a significant role in the risk of the catheter becoming infected¹¹³ and it is recommended that the femoral site be avoided if possible.¹¹⁴ Hand disinfection should be performed before placement or manipulation of vascular catheters.¹¹⁵ Maximal sterile

Prevention of other device-associated coagulase-negative staphylococcal infections

Many surgically implanted prosthetic device infections can be prevented by strict adherence to recommendations for the prevention of surgical site infections. A complete description of these guidelines is beyond the scope of this monograph. Further information is available in the section of this issue on staphylococcal surgical site infections by Jhung and Jernigan and in the CDC Hospital Infection Control Practices Advisory Committee (HICPAC) guideline on prevention of surgical site infections.

Management of infections caused by coagulase-negative staphylococci

If prevention of these infections has been unsuccessful then it becomes imperative for the clinician to offer optimum therapy. A number of factors influence clinical decisions regarding the management of CNS device-associated infections including the need for the device, the clinical condition of the patient and anticipated course of any underlying disease, morbidity associated with device removal, antimicrobial susceptibility, and antimicrobial pharmacokinetic/dynamic considerations. Luckily,

Antimicrobial resistance in coagulase-negative staphylococci

Antistaphylococcal antibiotics are covered more fully in another article in this issue. Table 2 summarizes information regarding antistaphylococcal antibiotics, resistance rates, and mechanisms of resistance. Briefly, when dealing with antimicrobial resistance in CNS, it is useful to distinguish hospital-acquired strains from community strains. Typically, those isolates causing disease in the community have lower rates of resistance than isolates acquired in the hospital environment.159, 160

Summary

The CNS, in particular S epidermidis, are uniquely qualified pathogens of modern medical care. They typically reside harmlessly on human skin and mucus membranes as a prominent part of the normal flora. However, this environmental niche gives them ready access to prosthetic devices that traverse the dermal tissues or are surgically implanted. Once these organisms gain access to the device, they are able to adhere and proliferate. S epidermidis is able to elaborate a thick, tenacious biofilm and

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Coagulase-Negative Staphylococcal Infections

Section snippets

Clinical syndromes and epidemiology

Intravascular catheter infections

Vascular graft infection

Endocarditis

Cardiac devices

Prosthetic joint infections

Central nervous system shunt infections

Surgical site infections

Infections involving other prosthetic devices

Coagulase-negative staphylococcal infections in neonates

Staphylococcus Saprophyticus

Pathogenesis and virulence traits

Clinical microbiology and molecular typing

Prevention of coagulase-negative staphylococcal infection

Prevention of intravascular catheter coagulase-negative staphylococcal infections

Prevention of other device-associated coagulase-negative staphylococcal infections

Management of infections caused by coagulase-negative staphylococci

Antimicrobial resistance in coagulase-negative staphylococci

Summary

J Hosp Infect

Lancet Infect Dis

Microbes Infect

Lancet Infect Dis

J Hosp Infect

Clin Microbiol Infect

Lancet

Infect Dis Clin North Am

Am J Med

Chest

Int J Infect Dis

Clin Microbiol Infect

Semin Pediatr Infect Dis

FEMS Microbiol Lett

Int J Antimicrob Agents

Microbes Infect

Report upon micro-organisms in surgical diseases

Br Med J

Staphylococcus epidermidis and other coagulase- negative staphylococci

Coagulase-negative staphylococci

The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults

Clin Infect Dis

Coagulase-negative staphylococci: pathogens associated with medical progress

Clin Infect Dis

Infections of intravascular catheters and vascular devices

Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989. National Nosocomial Infections Surveillance System

Am J Med

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

Distribution and persistence of Staphylococcus and Micrococcus species and other aerobic bacteria on human skin

Appl Microbiol

Natural populations of the genus Staphylococcus

Annu Rev Microbiol

Staphylococcus and biofilms

Mol Microbiol

New aspects of staphylococcal infections: emergence of coagulase-negative staphylococci as pathogens

Antonie Van Leeuwenhoek

Coagulase-negative staphylococci: role as pathogens

Annu Rev Med

Biofilm formation in medical device-related infection

Int J Artif Organs

Nosocomial bloodstream infections

Diagnosis of catheter-related bloodstream infection

Curr Infect Dis Rep

Guidelines for the prevention of intravascular catheter-related infections. Centers for disease control and prevention

MMWR Recomm Rep

Infections associated with intravascular catheters

Economic evaluation and catheter-related bloodstream infections

Emerg Infect Dis

Coagulase-negative staphylococcal infections; an update regarding recognition and management

The positive predictive value of isolating coagulase-negative staphylococci from blood cultures

Clin Infect Dis

Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm

J Clin Microbiol

Differences in time to positivity can affect the negative predictive value of blood cultures drawn through a central venous catheter

Intensive Care Med

Difference in time to detection: a simple method to differentiate catheter-related from non-catheter-related bloodstream infection in immunocompromised pediatric patients

Clin Infect Dis

Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections

Ann Intern Med