Infection due to coagulase-negative staphylococci: Epidemiology, microbiology, and pathogenesis
- JoAnn M Tufariello, MD, PhD
JoAnn M Tufariello, MD, PhD
- Albert Einstein College of Medicine
- Franklin D Lowy, MD
Franklin D Lowy, MD
- Professor of Medicine and Pathology & Cell Biology (in Epidemiology)
- Columbia University, College of Physicians and Surgeons
- Section Editors
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Coagulase-negative staphylococci (CoNS) are among the most frequent constituents of normal skin flora [1,2]. These organisms are common contaminants in clinical specimens as well as increasingly recognized as agents of clinically significant infection, including bacteremia and endocarditis . Patients at particular risk for CoNS infection include those with prosthetic devices (eg, pacemakers, intravascular catheters) and immunocompromised hosts.
The epidemiology, microbiology, and pathogenesis of coagulase-negative staphylococci will be reviewed here. Issues related to clinical manifestations and treatment of CoNS infections are discussed separately. (See "Infection due to coagulase-negative staphylococci: Clinical manifestations" and "Infection due to coagulase-negative staphylococci: Treatment".)
Use of intravascular devices is a major contributor to bloodstream infections caused by coagulase-negative staphylococci (CoNS).
Data from the National Nosocomial Infections Surveillance (NNIS) system collected between 1992 and 1997 revealed that CoNS accounted for 36 percent of all bloodstream isolates in intensive care units, making these organisms the most common cause of nosocomial bloodstream infections . A survey from the Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE) database of nosocomial bloodstream infections in United States hospitals between 1995 and 2002 also identified CoNS as the most common cause of hospital-acquired bloodstream infections, accounting for 31 percent of cases .
Among patients with blood cultures positive for CoNS, the fraction with a significant bloodstream infection ranges from 12 to 25 percent of cases [6-9]. Such distinction is important for clinical management. (See 'Infection versus contamination' below.)
- Roth RR, James WD. Microbial ecology of the skin. Annu Rev Microbiol 1988; 42:441.
- Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin Microbiol Rev 2014; 27:870.
- Chu VH, Woods CW, Miro JM, et al. Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis. Clin Infect Dis 2008; 46:232.
- Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27:887.
- Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39:309.
- Souvenir D, Anderson DE Jr, Palpant S, et al. Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J Clin Microbiol 1998; 36:1923.
- Kirchhoff LV, Sheagren JN. Epidemiology and clinical significance of blood cultures positive for coagulase-negative staphylococcus. Infect Control 1985; 6:479.
- Weinstein MP, Towns ML, Quartey SM, et al. 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 1997; 24:584.
- Herwaldt LA, Geiss M, Kao C, Pfaller MA. The positive predictive value of isolating coagulase-negative staphylococci from blood cultures. Clin Infect Dis 1996; 22:14.
- Hamory BH, Parisi JT, Hutton JP. Staphylococcus epidermidis: a significant nosocomial pathogen. Am J Infect Control 1987; 15:59.
- Leeming JP, Holland KT, Cunliffe WJ. The microbial ecology of pilosebaceous units isolated from human skin. J Gen Microbiol 1984; 130:803.
- Pfaller MA, Herwaldt LA. Laboratory, clinical, and epidemiological aspects of coagulase-negative staphylococci. Clin Microbiol Rev 1988; 1:281.
- Gemmell CG. Virulence characteristics of Staphylococcus epidermidis. J Med Microbiol 1986; 22:287.
- Males BM, Rogers WA Jr, Parisi JT. Virulence factors of biotypes of Staphylococcus epidermidis from clinical sources. J Clin Microbiol 1975; 1:256.
- Wallmark G, Arremark I, Telander B. Staphylococcus saprophyticus: a frequent cause of acute urinary tract infection among female outpatients. J Infect Dis 1978; 138:791.
- Ebright JR, Penugonda N, Brown W. Clinical experience with Staphylococcus lugdunensis bacteremia: a retrospective analysis. Diagn Microbiol Infect Dis 2004; 48:17.
- Trülzsch K, Rinder H, Trcek J, et al. "Staphylococcus pettenkoferi," a novel staphylococcal species isolated from clinical specimens. Diagn Microbiol Infect Dis 2002; 43:175.
- Loïez C, Wallet F, Pischedda P, et al. First case of osteomyelitis caused by "Staphylococcus pettenkoferi". J Clin Microbiol 2007; 45:1069.
- Mammina C, Bonura C, Verde MS, et al. A Fatal Bloodstream Infection by Staphylococcus pettenkoferi in an Intensive Care Unit Patient. Case Rep Crit Care 2011; 2011:612732.
- Khatib R, Riederer KM, Clark JA, et al. Coagulase-negative staphylococci in multiple blood cultures: strain relatedness and determinants of same-strain bacteremia. J Clin Microbiol 1995; 33:816.
- Christensen GD, Bisno AL, Parisi JT, et al. Nosocomial septicemia due to multiply antibiotic-resistant Staphylococcus epidermidis. Ann Intern Med 1982; 96:1.
- Rogers KL, Fey PD, Rupp ME. Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 2009; 23:73.
- Baird-Parker AC. Staphylococci and their classification. Ann N Y Acad Sci 1965; 128:4.
- Kloos WE, Schleifer KH. Simplified scheme for routine identification of human Staphylococcus species. J Clin Microbiol 1975; 1:82.
- Gemmell CG, Dawson JE. Identification of coagulase-negative staphylococci with the API staph system. J Clin Microbiol 1982; 16:874.
- Kloos WE, Wolfshohl JF. Identification of Staphylococcus species with the API STAPH-IDENT system. J Clin Microbiol 1982; 16:509.
- Hussain Z, Stoakes L, Stevens DL, et al. Comparison of the MicroScan system with the API Staph-Ident system for species identification of coagulase-negative staphylococci. J Clin Microbiol 1986; 23:126.
- Bannerman TL, Kleeman KT, Kloos WE. Evaluation of the Vitek Systems Gram-Positive Identification card for species identification of coagulase-negative staphylococci. J Clin Microbiol 1993; 31:1322.
- Carretto E, Barbarini D, Couto I, et al. Identification of coagulase-negative staphylococci other than Staphylococcus epidermidis by automated ribotyping. Clin Microbiol Infect 2005; 11:177.
- Gribaldo S, Cookson B, Saunders N, et al. Rapid identification by specific PCR of coagulase-negative staphylococcal species important in hospital infection. J Med Microbiol 1997; 46:45.
- Martineau F, Picard FJ, Roy PH, et al. Species-specific and ubiquitous DNA-based assays for rapid identification of Staphylococcus epidermidis. J Clin Microbiol 1996; 34:2888.
- Mendoza M, Meugnier H, Bes M, et al. Identification of Staphylococcus species by 16S-23S rDNA intergenic spacer PCR analysis. Int J Syst Bacteriol 1998; 48 Pt 3:1049.
- Mellmann A, Becker K, von Eiff C, et al. Sequencing and staphylococci identification. Emerg Infect Dis 2006; 12:333.
- Poyart C, Quesne G, Boumaila C, Trieu-Cuot P. Rapid and accurate species-level identification of coagulase-negative staphylococci by using the sodA gene as a target. J Clin Microbiol 2001; 39:4296.
- Becker K, Harmsen D, Mellmann A, et al. Development and evaluation of a quality-controlled ribosomal sequence database for 16S ribosomal DNA-based identification of Staphylococcus species. J Clin Microbiol 2004; 42:4988.
- Kloos WE, Bannerman TL. Update on clinical significance of coagulase-negative staphylococci. Clin Microbiol Rev 1994; 7:117.
- Tagini F, Greub G. Bacterial genome sequencing in clinical microbiology: a pathogen-oriented review. Eur J Clin Microbiol Infect Dis 2017.
- Tewhey R, Gu B, Kelesidis T, et al. Mechanisms of linezolid resistance among coagulase-negative staphylococci determined by whole-genome sequencing. MBio 2014; 5:e00894.
- Roach DJ, Burton JN, Lee C, et al. A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota. PLoS Genet 2015; 11:e1005413.
- Argemi X, Martin V, Loux V, et al. Whole-Genome Sequencing of Seven Strains of Staphylococcus lugdunensis Allows Identification of Mobile Genetic Elements. Genome Biol Evol 2017; 9.
- Conlan S, Mijares LA, NISC Comparative Sequencing Program, et al. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biol 2012; 13:R64.
- Deurenberg RH, Bathoorn E, Chlebowicz MA, et al. Application of next generation sequencing in clinical microbiology and infection prevention. J Biotechnol 2017; 243:16.
- Bertelli C, Greub G. Rapid bacterial genome sequencing: methods and applications in clinical microbiology. Clin Microbiol Infect 2013; 19:803.
- Wyres KL, Conway TC, Garg S, et al. WGS Analysis and Interpretation in Clinical and Public Health Microbiology Laboratories: What Are the Requirements and How Do Existing Tools Compare? Pathogens 2014; 3:437.
- Tang P, Croxen MA, Hasan MR, et al. Infection control in the new age of genomic epidemiology. Am J Infect Control 2017; 45:170.
- Didelot X, Bowden R, Wilson DJ, et al. Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 2012; 13:601.
- Claydon MA, Davey SN, Edwards-Jones V, Gordon DB. The rapid identification of intact microorganisms using mass spectrometry. Nat Biotechnol 1996; 14:1584.
- Clark AE, Kaleta EJ, Arora A, Wolk DM. Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin Microbiol Rev 2013; 26:547.
- Dupont C, Sivadon-Tardy V, Bille E, et al. Identification of clinical coagulase-negative staphylococci, isolated in microbiology laboratories, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and two automated systems. Clin Microbiol Infect 2010; 16:998.
- Carpaij N, Willems RJ, Bonten MJ, Fluit AC. Comparison of the identification of coagulase-negative staphylococci by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and tuf sequencing. Eur J Clin Microbiol Infect Dis 2011; 30:1169.
- Loonen AJ, Jansz AR, Bergland JN, et al. Comparative study using phenotypic, genotypic, and proteomics methods for identification of coagulase-negative staphylococci. J Clin Microbiol 2012; 50:1437.
- Kassim A, Pflüger V, Premji Z, et al. Comparison of biomarker based Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and conventional methods in the identification of clinically relevant bacteria and yeast. BMC Microbiol 2017; 17:128.
- Elamin WF, Ball D, Millar M. Unbiased species-level identification of clinical isolates of coagulase-negative Staphylococci: does it change the perspective on Staphylococcus lugdunensis? J Clin Microbiol 2015; 53:292.
- Camerer A, Kohlenberg A, Stefanik D, Seifert H. Evaluation of quantitative antibiotic susceptibility testing by Vitek 2 as a routine method to predict strain relatedness of coagulase-negative staphylococci isolated from blood cultures. J Clin Microbiol 2011; 49:3355.
- Seo SK, Venkataraman L, DeGirolami PC, Samore MH. Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia. Am J Med 2000; 109:697.
- Seybold U, Reichardt C, Halvosa JS, Blumberg HM. Clonal diversity in episodes with multiple coagulase-negative Staphylococcus bloodstream isolates suggesting frequent contamination. Infection 2009; 37:256.
- Al Wohoush I, Rivera J, Cairo J, et al. Comparing clinical and microbiological methods for the diagnosis of true bacteraemia among patients with multiple blood cultures positive for coagulase-negative staphylococci. Clin Microbiol Infect 2011; 17:569.
- Tolo I, Thomas JC, Fischer RS, et al. Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources? J Clin Microbiol 2016; 54:1711.
- Otto M. Staphylococcus epidermidis--the 'accidental' pathogen. Nat Rev Microbiol 2009; 7:555.
- Kocianova S, Vuong C, Yao Y, et al. Key role of poly-gamma-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis. J Clin Invest 2005; 115:688.
- von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect Dis 2002; 2:677.
- Worms R, Roujeau J, Du Buit H. The effect of a foreign body on the histological response to staphylococcal infection. In: Contributions to Microbiology and Immunology, Staphylococci and Staphylococcal Infections, Jelijaszewicz J (Ed), Karger, Basel 1973. Vol 1, p.258.
- McDERMOTT W. Microbial persistence. Yale J Biol Med 1958; 30:257.
- Zimmerli W, Waldvogel FA, Vaudaux P, Nydegger UE. Pathogenesis of foreign body infection: description and characteristics of an animal model. J Infect Dis 1982; 146:487.
- Bowden MG, Chen W, Singvall J, et al. Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis. Microbiology 2005; 151:1453.
- Herrmann M, Vaudaux PE, Pittet D, et al. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 1988; 158:693.
- Christensen GD, Simpson WA, Bisno AL, Beachey EH. Experimental foreign body infections in mice challenged with slime-producing Staphylococcus epidermidis. Infect Immun 1983; 40:407.
- Ishak MA, Gröschel DH, Mandell GL, Wenzel RP. Association of slime with pathogenicity of coagulase-negative staphylococci causing nosocomial septicemia. J Clin Microbiol 1985; 22:1025.
- Davenport DS, Massanari RM, Pfaller MA, et al. Usefulness of a test for slime production as a marker for clinically significant infections with coagulase-negative staphylococci. J Infect Dis 1986; 153:332.
- Lyte M, Freestone PP, Neal CP, et al. Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 2003; 361:130.
- Mack D, Fischer W, Krokotsch A, 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; 178:175.
- Götz F. Staphylococcus and biofilms. Mol Microbiol 2002; 43:1367.
- Heilmann C, Schweitzer O, Gerke C, et al. Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis. Mol Microbiol 1996; 20:1083.
- Wang R, Khan BA, Cheung GY, et al. Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J Clin Invest 2011; 121:238.
- Cheung GY, Joo HS, Chatterjee SS, Otto M. Phenol-soluble modulins--critical determinants of staphylococcal virulence. FEMS Microbiol Rev 2014; 38:698.
- Qin L, Da F, Fisher EL, et al. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis. PLoS Pathog 2017; 13:e1006153.
- Nguyen TH, Park MD, Otto M. Host Response to Staphylococcus epidermidis Colonization and Infections. Front Cell Infect Microbiol 2017; 7:90.
- Diep BA, Gill SR, Chang RF, et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 2006; 367:731.
- Otto M. Staphylococcus epidermidis pathogenesis. Methods Mol Biol 2014; 1106:17.
- Iwase T, Uehara Y, Shinji H, et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010; 465:346.