Treatment of infections due to coagulase-negative staphylococci
- 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
- 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 part of the normal flora of human skin . These organisms have relatively low virulence but are increasingly recognized as agents of clinically significant infection of the bloodstream and other sites.
Risk factors for CoNS infection include the presence of foreign devices (such as intravascular catheters) and immune compromise. Treatment of CoNS infections can be challenging given limitations of antimicrobial resistance and the frequent presence of foreign material.
Issues related to antimicrobial resistance and treatment of CoNS infections will be reviewed here. The epidemiology, microbiology, pathogenesis, and clinical manifestations of CoNS are discussed separately. (See "Epidemiology, microbiology, and pathogenesis of coagulase-negative staphylococci" and "Clinical manifestations of infection due to coagulase-negative staphylococci".)
Microbiology — Resistance to methicillin and semisynthetic penicillins has been observed in more than 80 percent of coagulase-negative staphylococcal (CoNS) isolates . Such isolates are often resistant to multiple classes of antibiotics in addition to beta-lactams. The genes responsible for resistance are often found on plasmids, facilitating horizontal exchange of resistance genes among strains.
The mecA gene encoding a low-affinity penicillin-binding protein (PBP 2a) is responsible for mediating methicillin or oxacillin resistance in CoNS, as in Staphylococcus aureus . This resistance is heterotypic, since only a minority of the bacterial population (as few as one in 103 or 106 organisms) expresses the resistant phenotype; this makes detection of resistance especially challenging . (See "Microbiology of methicillin-resistant Staphylococcus aureus".)
- Roth RR, James WD. Microbial ecology of the skin. Annu Rev Microbiol 1988; 42:441.
- Diekema DJ, Pfaller MA, Schmitz FJ, et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 2001; 32 Suppl 2:S114.
- Ryffel C, Tesch W, Birch-Machin I, et al. Sequence comparison of mecA genes isolated from methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Gene 1990; 94:137.
- Archer GL, Climo MW. Antimicrobial susceptibility of coagulase-negative staphylococci. Antimicrob Agents Chemother 1994; 38:2231.
- Archer GL, Armstrong BC. Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis. J Infect Dis 1983; 147:642.
- Kernodle DS, Barg NL, Kaiser AB. Low-level colonization of hospitalized patients with methicillin-resistant coagulase-negative staphylococci and emergence of the organisms during surgical antimicrobial prophylaxis. Antimicrob Agents Chemother 1988; 32:202.
- Archer GL, Dietrick DR, Johnston JL. Molecular epidemiology of transmissible gentamicin resistance among coagulase-negative staphylococci in a cardiac surgery unit. J Infect Dis 1985; 151:243.
- Archer GL. Alteration of cutaneous staphylococcal flora as a consequence of antimicrobial prophylaxis. Rev Infect Dis 1991; 13 Suppl 10:S805.
- Levy MF, Schmitt DD, Edmiston CE, et al. Sequential analysis of staphylococcal colonization of body surfaces of patients undergoing vascular surgery. J Clin Microbiol 1990; 28:664.
- Tenover FC, Jones RN, Swenson JM, et al. Methods for improved detection of oxacillin resistance in coagulase-negative staphylococci: results of a multicenter study. J Clin Microbiol 1999; 37:4051.
- National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. Tenth Informational Supplement. NCCLS document M100-S17 vol. 27. No. 1, 2007. National Committee for Clinical Laboratory Standards, Wayne, PA.
- Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Nineteenth Informational Supplement. CLSI document M100-S19; 29, Clinical and Laboratory Standards Institute, Wayne, PA 2009.
- Maranan MC, Moreira B, Boyle-Vavra S, Daum RS. Antimicrobial resistance in staphylococci. Epidemiology, molecular mechanisms, and clinical relevance. Infect Dis Clin North Am 1997; 11:813.
- Archer GL, Pennell E. Detection of methicillin resistance in staphylococci by using a DNA probe. Antimicrob Agents Chemother 1990; 34:1720.
- Ubukata K, Nakagami S, Nitta A, et al. Rapid detection of the mecA gene in methicillin-resistant staphylococci by enzymatic detection of polymerase chain reaction products. J Clin Microbiol 1992; 30:1728.
- Unal S, Hoskins J, Flokowitsch JE, et al. Detection of methicillin-resistant staphylococci by using the polymerase chain reaction. J Clin Microbiol 1992; 30:1685.
- Horstkotte MA, Knobloch JK, Rohde H, Mack D. Rapid detection of methicillin resistance in coagulase-negative staphylococci by a penicillin-binding protein 2a-specific latex agglutination test. J Clin Microbiol 2001; 39:3700.
- Zbinden R, Ritzler M, Ritzler E, Berger-Bächi B. Detection of penicillin-binding protein 2a by rapid slide latex agglutination test in coagulase-negative staphylococci. J Clin Microbiol 2001; 39:412.
- Hussain Z, Stoakes L, Garrow S, et al. Rapid detection of mecA-positive and mecA-negative coagulase-negative staphylococci by an anti-penicillin binding protein 2a slide latex agglutination test. J Clin Microbiol 2000; 38:2051.
- Udo EE, Mokadas EM, Al-Haddad A, et al. Rapid detection of methicillin resistance in staphylococci using a slide latex agglutination kit. Int J Antimicrob Agents 2000; 15:19.
- Chambers HF. Methicillin-resistant staphylococci. Clin Microbiol Rev 1988; 1:173.
- Schwalbe RS, Stapleton JT, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 1987; 316:927.
- Sanyal D, Johnson AP, George RC, et al. Peritonitis due to vancomycin-resistant Staphylococcus epidermidis. Lancet 1991; 337:54.
- Veach LA, Pfaller MA, Barrett M, et al. Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990; 28:2064.
- Hanaki H, Kuwahara-Arai K, Boyle-Vavra S, et al. Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50. J Antimicrob Chemother 1998; 42:199.
- Cui L, Ma X, Sato K, et al. Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. J Clin Microbiol 2003; 41:5.
- Sieradzki K, Tomasz A. Gradual alterations in cell wall structure and metabolism in vancomycin-resistant mutants of Staphylococcus aureus. J Bacteriol 1999; 181:7566.
- Sieradzki K, Pinho MG, Tomasz A. Inactivated pbp4 in highly glycopeptide-resistant laboratory mutants of Staphylococcus aureus. J Biol Chem 1999; 274:18942.
- Nunes AP, Teixeira LM, Iorio NL, et al. Heterogeneous resistance to vancomycin in Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains: characterisation of glycopeptide susceptibility profiles and cell wall thickening. Int J Antimicrob Agents 2006; 27:307.
- Dunne WM Jr, Qureshi H, Pervez H, Nafziger DA. Staphylococcus epidermidis with intermediate resistance to vancomycin: elusive phenotype or laboratory artifact? Clin Infect Dis 2001; 33:135.
- Wong SS, Ho PL, Woo PC, Yuen KY. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance. Clin Infect Dis 1999; 29:760.
- Kelly S, Collins J, Maguire M, et al. An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit. J Antimicrob Chemother 2008; 61:901.
- Rybak MJ, Cappelletty DM, Moldovan T, et al. Comparative in vitro activities and postantibiotic effects of the oxazolidinone compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin against Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother 1998; 42:721.
- Chien JW, Kucia ML, Salata RA. Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin Infect Dis 2000; 30:146.
- Antony SJ, Diaz-Vasquez E, Stratton C. Clinical experience with linezolid in the treatment of resistant gram-positive infections. J Natl Med Assoc 2001; 93:386.
- Saravolatz LD, Stein GE, Johnson LB. Telavancin: a novel lipoglycopeptide. Clin Infect Dis 2009; 49:1908.
- Kratzer C, Rabitsch W, Hirschl AM, et al. In vitro activity of daptomycin and tigecycline against coagulase-negative staphylococcus blood isolates from bone marrow transplant recipients. Eur J Haematol 2007; 79:405.
- Sader HS, Streit JM, Fritsche TR, Jones RN. Antimicrobial susceptibility of gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002-2004). Clin Microbiol Infect 2006; 12:844.
- Flamm RK, Sader HS, Farrell DJ, Jones RN. Summary of ceftaroline activity against pathogens in the United States, 2010: report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program. Antimicrob Agents Chemother 2012; 56:2933.
- Flamm RK, Sader HS, Farrell DJ, Jones RN. Ceftaroline potency among 9 US Census regions: report from the 2010 AWARE Program. Clin Infect Dis 2012; 55 Suppl 3:S194.
- Ho TT, Cadena J, Childs LM, et al. Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy. J Antimicrob Chemother 2012; 67:1267.
- Rose WE, Schulz LT, Andes D, et al. Addition of ceftaroline to daptomycin after emergence of daptomycin-nonsusceptible Staphylococcus aureus during therapy improves antibacterial activity. Antimicrob Agents Chemother 2012; 56:5296.
- Sakoulas G, Moise PA, Casapao AM, et al. Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline. Clin Ther 2014; 36:1317.
- Aldridge KE, Schiro DD, Varner LM. In vitro antistaphylococcal activity and testing of RP 59500, a new streptogramin, by two methods. Antimicrob Agents Chemother 1992; 36:854.
- Eliopoulos GM. Antimicrobial agents for treatment of serious infections caused by resistant Staphylococcus aureus and enterococci. Eur J Clin Microbiol Infect Dis 2005; 24:826.
- Rubinstein E, Bompart F. Activity of quinupristin/dalfopristin against gram-positive bacteria: clinical applications and therapeutic potential. J Antimicrob Chemother 1997; 39 Suppl A:139.
- Stein A, Bataille JF, Drancourt M, et al. Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole). Antimicrob Agents Chemother 1998; 42:3086.
- Levitz RE, Quintiliani R. Trimethoprim-sulfamethoxazole for bacterial meningitis. Ann Intern Med 1984; 100:881.
- Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med 1992; 117:390.
- Frame PT, McLaurin RL. Treatment of CSF shunt infections with intrashunt plus oral antibiotic therapy. J Neurosurg 1984; 60:354.
- Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005; 111:e394.
- Archer GL, Johnston JL. Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides. Antimicrob Agents Chemother 1983; 24:70.
- Archer GL, Scott J. Conjugative transfer genes in staphylococcal isolates from the United States. Antimicrob Agents Chemother 1991; 35:2500.
- Mandell GL, Moorman DR. Treatment of experimental staphylococcal infections: effect of rifampin alone and in combination on development of rifampin resistance. Antimicrob Agents Chemother 1980; 17:658.
- Høiby N, Jarløv JO, Kemp M, et al. Excretion of ciprofloxacin in sweat and multiresistant Staphylococcus epidermidis. Lancet 1997; 349:167.
- Thomson KS, Sanders CC, Hayden ME. In vitro studies with five quinolones: evidence for changes in relative potency as quinolone resistance rises. Antimicrob Agents Chemother 1991; 35:2329.