Coagulase-Negative Staphylococcus

Coagulase-negative staphylococci (CoNS) species are skin commensal bacteria typically encountered in hospital settings.¹ In the United States, they are the most common cause of health care-related infections.² There are more than 30 species of CoNS, and approximately 50% are known to colonize in humans.² Coagulase-negative staphylococci typically causes infection when there is a foreign body such as a medical device or prosthetic in place.² It is frequently resistant to methicillin and other antibiotics, which can make it challenging to manage.^1-3

Staphylococcus epidermidis is the most common CoNS.³ Although it is not harmful on the surface of skin, when S. epidermidis is inadvertently introduced into the body via a medical device, prosthetic, or procedure, it can cause serious infection, particularly in patients who are immunocompromised, immunosuppressed, critically ill, or hospitalized long-term.³ Staphylococcus saprophyticus is also a common CoNS. It is responsible for 10% to 15% of uncomplicated, community-acquired urinary tract infections.⁴

Coagulase-negative staphylococci infection may not produce a fever or other signs of systemic infection.² The signs and symptoms of CoNS infection vary based on the affected body part or system, as well as the surgical procedure, device, and technologies implicated in the infection (Table).⁵

Table. Signs and symptoms of coagulase-negative staphylococci infections⁵

Diagnostic Workup

Because they are normal skin flora, CoNS are the most common blood culture contaminant.² This makes it challenging to determine whether a positive CoNS culture indicates a true infection or merely contamination. Positive blood cultures that detect multiple CoNS strains are likely to be a result of contamination.² In addition to assessing for the signs and symptoms of a CoNS infection, the diagnosis may be established by documenting more than 100 white blood cells/mL in dialysate fluid and recovering CoNS in fluid cultures.⁵ The time to blood culture positivity, quantitative blood cultures, and the presence of multiple positive cultures also can be used to help determine if a positive culture represents a true infection.²

Differential Diagnosis of Coagulase-Negative Staphylococcus

Coagulase-negative staphylococci needs to be differentiated from positive staphylococci pathogens, primarily Staphylococcus aureus. S. aureus is the cause of 30% of surgical site infections in the United States and accounts for approximately 50% of infections that result from orthopedic and neurosurgical interventions.²

Perhaps the greatest challenge in the differential diagnosis is to rule out contamination of blood cultures, particularly in patients with severe immunosuppression or who have prosthetic joints or indwelling medical devices.⁶ Organisms that in the past have almost always been interpreted as “contaminants” could cause bacteremia in such patients.⁶ Proper blood collection procedures and rapid pathogen identification are crucial when evaluating a patient with suspected CoNS infection.⁶

According to the American Society of Microbiology, the coagulase test can be used to differentiates strains of S. aureus from S. epidermidis and other coagulase-negative species.⁷ The 2 types of coagulase tests are the slide test and the tube test; on each test, clumping or clots of any size indicate a positive response.⁷ While the slide test is simple and provides results within a few seconds, it is prone to false positives. The tube test is more definitive but can take up to 24 hours to provide results.⁷ Both tests require fresh bacterial cultures (24 hours or younger) grown in noninhibitory media such as chocolate agar, blood agar, or trypticase soy agar.⁷

Risks & Complications

Patients who undergo solid-organ or hematopoietic stem cell transplant are at risk for developing CoNS infections due to immunosuppression, mucosal or skin breakdown, or intravascular catheterization.⁵ Premature infants are particularly vulnerable to CoNS-induced infections, including pneumonia, omphalitis, and abscesses.⁸ In older children, CoNS may cause endophthalmitis and keratitis, often after eye trauma.⁸ Coagulase-negative staphylococci may also contribute to the development of sepsis, and preterm neonates are especially vulnerable to these types of infections.⁹ Compared with the general population, older adults with significant comorbidities are also at higher risk for CoNS infections.¹⁰

Complications of CoNS infections related to an implant or invasive procedures are typically site-specific. However, bloodstream infections related to a foreign body are common.⁹ Patients with CoNS bloodstream infections have significantly longer intensive care unit and/or hospital stays and higher mortality rates and hospital costs compared with uninfected patients.⁹

Antibiotic resistance is a serious treatment-related complication of CoNS. Coagulase-negative staphylococci often are resistant to oxacillin/methicillin, penicillin, ciprofloxacin, gentamicin, erythromycin, and clindamycin, which requires the use of second-line antibiotics such as linezolid, vancomycin, or daptomycin.¹⁰ While the optimal duration of antibiotic treatment for a CoNS infection has not been determined, some evidence suggests that for uncomplicated intravascular catheter infections, including those caused by CoNS, there are no significant differences between shorter vs longer treatment.¹¹

References

1. Argemi X, Hansmann Y, Prola K, Prévost G. Coagulase-negative staphylococci pathogenomics. Int J Mol Sci. 2019;20(5):1215. doi:10.3390/ijms20051215
2. Chambers HF, Sakoulas G. Staphylococcal infections. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 26th ed. Elsevier; 2020:1862-1868.e2.
3. Soumya KR, Philip S, Sugathan S, Mathew J, Radhakrishnan EK. Virulence factors associated with coagulase negative staphylococci isolated from human infections. 3 Biotech. 2017;7(2):140. doi:10.1007/s13205-017-0753-2
4. Dubbs SB, Sommerkamp SK. Evaluation and management of urinary tract infection in the emergency department. Emerg Med Clin North Am. 2019;37(4):707-723. doi:10.1016/j.emc.2019.07.007
5. Rupp ME, Fey PD. Staphylococcus epidermidis and other coagulase-negative staphylococci. In: Bennett, JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:2432-2443.e7.
6. Pence MA, McElvania TeKippe E, Burnham CA. Diagnostic assays for identification of microorganisms and antimicrobial resistance determinants directly from positive blood culture broth. Clin Lab Med. 2013;33(3):651-84. doi:10.1016/j.cll.2013.03.010
7. Coagulase test protocol. Katz DS. American Society for Microbiology. Published November 11, 2010. Accessed April 24, 2023. https://asm.org/ASM/media/Protocol-Images/Coagulase-Test-Protocol.pdf?ext=.pdf
8. Toltzis P. Coagulase-negative staphylococci and micrococcaceae. In: Long S, Prober CG, Fischer M, Kimberlin DW, eds. Principles and Practice of Pediatric Infectious Diseases. 6th ed. 2023; 724-729.e5.
9. Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin Microbiol Rev. 2014;27(4):870-926. doi:10.1128/CMR.00109-13
10. Michels R, Last K, Becker SL, Papan C. Update on coagulase-negative staphylococci: What the clinician should know. Microorganisms. 2021;9(4):830. doi:10.3390/microorganisms9040830
11. Muff S, Tabah A, Que YA, et al. Short-course versus long-course systemic antibiotic treatment for uncomplicated intravascular catheter-related bloodstream infections due to gram-negative bacteria, enterococci or coagulase-negative staphylococci: A systematic review. Infect Dis Ther. 2021;10(3):1591-1605. doi:10.1007/s40121-021-00464-0