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Staphylococcus Lugdunensis: The Coagulase-negative Staphylococcus You Don't Want to Ignore


Elizabeth Babu, John Oropello Expert Rev Anti Infect Ther. 2011;9(10):901-907.

Abstract and Introduction


Abstract

Staphylococcus lugdunensis is a virulent coagulase-negative staphylococcus (CoNS) that behaves like Staphylococcus aureus. Toxic shock syndrome, osteomyelitis, septic arthritis and postoperative endopthalmitis have been observed. Endocarditis complicated by heart failure, periannular abscess formation and embolic phenomenon have brought particular attention to this CoNS. Mortality rates for endocarditis appear higher when compared with other CoNS. Owing to the laboratory methods used, identifi cation may be misleading. lactam antimicrobials are recommended pending sensitivities. Evaluation for endocarditis should be pursued in bacteremic patients due to its pathogenic potential.

Epidemiology
According to the most recent SENTRY Antimicrobial Surveillance Program,[1] which monitors predominant pathogens and antimicrobial resistance in the USA, Canada, Latin America and Europe, Staphylococcus lugdunensis was the seventh most common coagulase-negative staphylococcus (CoNS) species isolated in bloodstream infections during the 12-month study period in 1997. To date, the frequency of isolation of S. lugdunensis among CoNS from clinical specimens has been reported in a few isolated studies. Rates range from less than 1% in Denmark[2] and Korea,[3,4] approximately 3% in Japan,[5] 6% in Argentina[6] and from 3 to as high as 7% in the USA.[7,8] S. lugdunensis is normally found as part of human skin flora and has been identified in cultures from the entire body.[9] Studies carried out to look into specific areas of colonization have not been very thorough. The most comprehensive study obtained 525 cultures from eight sites in 75 healthy subjects.[10] Swabs from the groin, toes and axilla yielded S. lugdunensis most frequently. Further studies need to be performed to clarify if the organism has a preferred site of colonization, if the site is different in hospitalized patients and if these sites are a permanent or transient habitat.

History
In 1988, the first description of two new species of Staphylococcus, S. lugdunensis and Staphlococcus schleiferi, was published by Freney et al..[11] These two species were obtained from a collection of unidentified

Staphylococcal strains at The French National Reference Center for Staphylococci. In total, 11 strains were identified as the new genomic species described formally as Staphylococcus lugdunensis. It assumed the Latin name of Lyon, the French city where the organism was first identified. Of the 11 strains, five were obtained from blood, and one each from an intrauterine device, thoracic drain, umbilicus, axillary lymph node, abscess drain and an unknown site. The 11 strains studied were variable depending on the culture medium and the time of incubation. All strains were Gram-positive cocci, 0.81.0 m in diameter, occurring singly, in pairs, small clusters or chains. All strains produced catalase and did not produce coagulase or oxidase. Enterotoxins A, B and C, toxic shock syndrome toxin (TSST) and exfoliative toxin production were not described with this pathogen. All strains were susceptible to oxacillin and penicillin.

Clinical Features
S. lugdunensis has been associated with a wide variety of infections, including cardiovascular infections, osteomyelitis and prosthetic joint infections, bloodstream infections, skin and soft-tissue infections, central nervous infections, peritonitis, endopthalmitis and urinary tract infections. S. lugdunensis has been described as the etiology of cardiovascular infections including severe native and prosthetic valve endocarditis, device-related endocarditis, myocarditis[12] and infected cardiac myxoma.[13] In general, CoNS are unusual causes of native valve endocarditis but are one of the leading causes of prosthetic material-associated endocarditis. The clinical course is subtle, subacute or even chronic without fulminant signs of infection.[14] Infections with CoNS are typically not associated with abscess formation, heart failure or embolic phenomenon. Furthermore, compared with Staphylococcus aureus, CoNS are more amendable to medical and/or surgical therapy and typically have shorter courses with better clinical outcomes.[15] The reports of S. lugdunensis are quite different. S. lugdunensis has been reported as the cause of endocarditis in 67 cases since 1988.[16] Reported cases have been mostly community acquired but not associated with injection drug use. This reporting may represent a significant bias since cases with complicated courses and poor outcomes tend to be published. However, the cases provide a spectrum of complications including acute onset, heart failure,[17] periannular abscess formation,[18] peripheral embolism[19] and shock, which typically is not described in CoNS. In addition, clinical outcomes mimic cases involving S. aureus native and prosthetic valve endocarditis. A prospective cohort study of two centers described their experience with ten cases of S. lugdunensis endocarditis and, in addition, performed a combined analysis of 59 cases in a literature review. [20] Their findings noted that in native valve endocarditis the mitral valve is involved the majority of the time, surgery was required in 51% of the cases and the mortality rate reached as high as 42%. In prosthetic valve endocarditis the aortic valve was most frequently affected, also required surgical intervention, and the mortality rate was 78%. Pacemaker/defibrillator lead endocarditis caused by S. lugdunensis was associated with better prognosis when antibiotic treatment was combined with a surgical removal of the device. Therefore, lead extraction should be performed without delay as recommended by the American Heart Association scientific statement on nonvalvular cardiovascular device-related infections.[21]

Native valve endocarditis has been a consequence of infection originating at other sites, including skin and soft-tissue infections,[9] hemodialysis,[22] vascular catheters,[23,24] coronary angioplasty, vasectomy,[25] kidney transplantation[26] and prosthetic joint infections.[27] Transesophageal echocardiogram (TEE) is the gold standard for identification of intracardiac vegetations with a sensitivity of 96% compared with transthoracic echocardiogram (TTE) of only 30%.[28] TTE can lead to falsenegative results and a delay in appropriate therapy. TEE should be considered as the initial imaging modality in endocarditis.[21] Although uncommon, S. lugdunensis is very destructive and plays a major role in infective endocarditis. Echocardiographic evaluation can change medical and surgical management and may improve clinical outcome in individuals with S. lugdunensis endocarditis. Therefore, evaluation with echocardiography should be pursued. The next most common serious infections are bone and joint infections, both native and prosthetic. Reports have included vertebral osteomyelitis,[29] disk space infection,[30] spondylodiscitis[31] and septic arthritis.[32] Following surgical procedures, both temporal bone osteomyelitis[33] and septic arthritis[34] have been described. Prosthetic joint infections[35,36] have been reported to manifest as early as 6 weeks to as late as 4 years after implantation. In a study looking at S. lugdunensis bacteremia in 63 patients, 15 (23.8%) had clinically significant bacteremia defined as positive blood cultures and systemic inflammatory response syndrome without an alternative explanation.[4] Of those with clinically significant bacteremia, the source was unknown in eight (53%) and associated with central venous catheters in five (33%) patients. In additiona, in this subset of patients, endocarditis was seen in four (26%) patients, two of whom had underlying valvular heart disease. Among the reports of S. lugdunensis, sepsis,[37] septic shock[38] and toxic shock syndrome have been described. A report described septic shock in a 71-year-old man after receiving platelet[39] and red cell transfusions for pancytopenia secondary to myelodysplasia. Blood cultures and cultures of the platelets yielded S. lugdunensis. The transfused blood was sterile and there was no evidence of allergic reaction to the blood products or any other source of infection. Toxic shock syndrome was described in a 33-year-old healthy woman 48 h after a tooth extraction with Gelfoam packing.[40] Blood and purulent maxillary sinus cultures were identified as S. lugdunensis. Tests for coagulase, TSST-1, staphylococcal enterotoxins AE and exfoliatin toxin A were negative. Neither S. aureus nor S. pyogenes were isolated from any samples of blood, urine, sputum, sinus or vaginal specimens from this patient. Fadel et al. examined the outcomes of 29 patients with a single S. lugdunensis positive blood culture.[41] From the chart review, the primary treating physician considered nine (31%) cases clinically significant, did not acknowledge the culture in 14 (48%), and disregarded the culture as a contaminant in six (21%) cases. Fadel et al. reclassified the cases based on defined criteria and found that 13 (45%) patients with a single positive blood culture had clinically significant bacteremia. Therefore, they concluded that all blood cultures for CoNS

should be screened for S. lugdunensis and isolation of this organism from one blood culture should not be assumed to be contamination. Skin and soft-tissue infection account for the majority of infections caused by S. lugdunensis. When isolated from a superficial infection it is more likely to be significant compared with S. epidermidis.[42] S. lugdunensis is well known to cause suppurative skin and soft-tissue infections including furuncles, cellulitis and abscesses.[43] Abscesses have mostly been reported to affect the perineal and inguinal area[44,45] and have usually been associated with surgical procedures. However, abscesses have also been described in nonlactating women.[46,47] One case of a severe acute necrotizing sinusitis complicated by periorbital cellulitis and ulceration through the maxillary sinus through the hard palate has been reported.[48] Pyomyoma after a cesarean section[49] and endometritis[50] has also been described. Infections of the CNS have included abscesses from dental infections, septic emboli from native valve endocarditis, multiple mycotic cerebral aneurysms[51] and meningitis from ventriculostomy and ventriculoperitoneal shunt infections.[52] The ventriculoperitoneal shunt infections occur both with an early and late onset.[53,54] Peritonitis has been described in a patient after cesarean section[55] and in a patient undergoing continuous peritoneal dialysis.[56] In a 4-year multicenter study looking at the species distribution of CoNS in patients with endopthalmitis, S. lugdunensis was the second most common CoNS after S. epidermidis.[57] In a series of postoperative endopthalmitis caused by S. lugdunensis, endopthalmitis was characterized by severe visual loss (hand motion or less) that occurred a mean 7.6 days after cataract surgery and necessitated pars plana viterectomy in three of the five cases.[58] The authors stated that compared with other CoNS, patients infected with S. lugdunensis were characterized by a worse final functional prognosis at 6 months and a higher frequency of viterectomy retinal detachment (60 vs 3%).

Pathogenesis
The toxins produced by S. aureus such as enterotoxins, exfoliatin and TSST have not been identified in any S. lugdunensis isolates despite the syndrome of toxic shock that has been reported. However, various virulence factors have been identified that may explain the similar pathogenic potential to S. aureus. Regions of homology to the S. aureus accessory gene regulator (agr) locus, the regulator of virulence factors, have been identified. This includes heat-stable -like hemolysin, which is similar to toxin in S. aureus. toxin enables the staphylococci to escape killing and digestion by the phagosomes. [59] Another similarity to S. aureus is S. lugdunensis' resistance to lysozyme. Lysozymes, abundant in the cytoplasmic granules of polymorphonuclear neutrophils, are enzymes created by the immune system that damage cell walls. S. lugdunensis possesses in its genome a homologous region to S. aureus that functions in lysozyme resistance. Known as OatA (Oacetyltransferase), this membrane-bound peptidoglycan prevents the binding of lysozyme to the cell wall, thereby averting the immune system.[60]

In addition to averting the immune system, S. lugdunensis has been found to have properties that promote tissue interaction. These properties include adhesins that promote binding to proteins found in host tissue. An investigation to identify these cell surface factors revealed that S. lugdunensis binds to collagen type I found primarily in scar tissue and collagen type IV found on the basal lamina the extracellular matrix on which the epithelial cell sits.[61] Binding to fibronectin, fibrinogen, laminin, vitronectin and plasminogen, key factors in cell adhesion and wound healing, has also been described. The production of von Willebrand factor-binding protein by this organism has been thought to be a contributing factor in the pathogenesis of endocarditis. This protein primarily functions to bind other proteins particularly involved in platelet adhesion following vascular injury. [62] These various adherence factors enable attachment to, and infection of, host tissue as well as synthetic surfaces. S. lugdunensis is also able to protect itself from the immune system via the production of biofilm. [63] Even though organisms may demonstrate susceptibility to an array of antimicrobials, infections can be very difficult to treat if organisms form and proliferate within biofilms. A biofilm is a polymeric matrix of cells, adherence proteins and polysaccharides in which microorganisms can replicate and thrive. This extracellular slime embeds onto host tissues or indwelling medical devices and is difficult to eradicate due to the high level of resistance to antimicrobial therapies as well as the production of factors that interfere with innate immune defenses. One mechanism of this glycocalyx is the ability to stimulate monocyte prostaglandin E2. Prostaglandin E2 modulates the immune system by inhibiting T-cell proliferation.[64]

Diagnosis
In contrast to S. aureus, S. lugdunensis is coagulase negative. Caution should be taken with the latex agglutination test since around 58% of strains of S. lugdunensis produce a bound coagulase.[11,61] Also known as clumping factor, on slide it can suggest that the organism produces coagulase and the technician can falsely identify the organism as S. aureus. S. lugdunensis does not produce coagulase and therefore in the test tube will always be coagulase negative. In addition, some automated identification systems fail to identify S. lugdunensis if the database lacks insufficient discriminatory biochemical reactions, such as ornithine decarboxylase.[65,66] Mateo et al. studied 17 isolates and S. lugdunensis was misidentified most frequently as S. haemolyticus.[67] Species misidentification rates were 5.9, 23.5 and 29.4% with the Crystal (Becton Dickinson, MD, USA), Vitek 2 (bioMrieux, Marcy l'Etoile, France) and Wider (Soria Melguizo SA, Madrid, Spain) systems, respectively. The ATB32-Staph system (bioMrieux) correctly identified all isolates. The Manual of Clinical Microbiology provides the list of systems that have S. lugdunensis in their database.[68] Molecular identification with ribotyping[69] and PCR amplification[70,71] is a rapid and effective alternative to conventional identification strategies. Morphologically, S. aureus and S. lugdunensis have a slight yellow pigmentation and on blood agar plates demonstrate hemolysis. Manual identification demonstrates positive catalase, pyrrolidonyl arylamidases and ornithine decarboxylase tests. Another feature of this organism is that it demonstrates colony variation. [72] Colony variation essentially means that isolates demonstrate mixed morphotypes. Strains can appear both smooth and glossy or rough and dull. In the laboratory this feature may suggest that there exists a mixed population of organisms such as you find in a contamination.

Coagulase-negative staphylococci are among the most frequently isolated bacteria in the clinical microbiology laboratory. These bacteria are normal inhabitants of human skin and mucous membranes and therefore one of the major challenges of daily diagnostic work is to distinguish clinically significant CoNS from contaminant strains. One should have a high degree of suspicion if the clinical course does not correlate with a CoNS organism on culture, especially from a sterile site. Fadel et al. found that 45% of cases with a single positive blood culture for S. lugdunensis were clinically significant.[41] This was defined as having prolonged fever, hypotension, leukocytosis, neutropenia or disseminated intravascular coagulopathy.[2] Many laboratories do not routinely identify CoNS to the species level and presume contamination unless requested. Being aware of these characteristics, including the increased probability of laboratory misidentification, is helpful in earlier recognition and appropriate management of S. lugdunensis infection.

Treatment
Most isolates of S. lugdunensis described have been sensitive to an array of antimicrobial therapy. However, there have been isolated case reports of resistance to erythromycin,[73] streptomycin,[73] tetracycline,[4] penicillin,[74,75] gentamicin,[55] ceftazidime,[55] aminoglycosides[20] and macrolides.[27] Development of resistance to ciprofloxacin[67] and rifampin in a patient on chronic treatment for septic arthritis, vertebral osteomyelitis and aortic and mitral valve endocarditis has been described.[76] -lactamase, the enzyme that confers resistance to -lactam antimicrobials such as penicillin, has been reported in the USA as well as in Europe. [55,77] The frequency of -lactamase in S. lugdunensis is between 7 and 24% in France,[78] 12% in Spain,[9] 15% in Sweden[79] and 2440% in the USA.[80,81] The mecA gene is part of the staphylococcal cassette chromosome that confers resistance to oxacillin and generally all -lactams. The mecA gene has been reported in several reports to date;[8284] the first in a neonate[80] with S. lugdunensis bacteremia associated with an intravascular catheter and the second isolate from a nasal swab.[81] Currently, the Clinical Laboratory and Standards Institute has recommended that S. lugdunensis isolates should be screened for the mecA gene by PCR or penicillinbinding protein 2A (PBP2a) by latex agglutination. Recently, a mecA-negative S. lugdunensis isolate resistant to all -lactams has been described.[85] In 2005, the breakpoints for oxacillin sensitivity were revised to follow the breakpoints for S. aureus: MICs of 2 g/ml are considered susceptible and MICs 4 g/ml are classified resistant.[86] Reports of vancomycin (a glycopeptide antimicrobial agent) resistance have not been documented to date. In a recent in vitro study based on MIC50/90 values, the newest glycopeptide telavancin demonstrated potent activity against S. lugdunensis.[87] The successful eradication of S. lugdunensis prosthetic joint infection with linezolid after failure of ciprofloxacin and rifampin has been reported.[88] In their prospective study of ten patients with S. lugdunensis endocarditis, Anguera et al. observed no difference in mortality between monotherapy (-lactam or vancomycin) and combination therapy (-lactam with an aminoglycoside or rifampin or cephalosporin and vancomycin with an aminoglycoside or rifampin or cephalosporin or carbapenem).[20] There is a lack of randomized controlled data on the efficacy of antimicrobial agents for S. lugdunensis infections. The Infectious Diseases Society of America guidelines for endocarditis recommends treatment based on in vitro susceptibility profiles and follow-up monitoring of the development of periannular extension or extracardiac spread of infection.[89] Empiric treatment with a -lactam agent should be appropriate. For patients

with penicillin allergies, vancomycin is an alternative. Source control with drainage of abscesses, early surgical intervention for valvular compromise and removal of intravascular catheters and pacemaker leads should be pursued. In addition, transesophageal echocardiograms to assess valvular involvement and CT scans to evaluate for embolic phenomena should be strongly considered.

Prognosis
S. lugdunensis, unlike other CoNS, is associated with a high rate of complications.

Expert Commentary & Five-year View


S. lugdunensis is a Gram-positive CoNS species normally found as part of human skin flora. Owing to an increased effort to identify all staphylococcus isolates, the number of S. lugdunensis isolates has increased. Depending on methods used, the laboratory can incorrectly identify S. lugdunensis as S. aureus or more problematic, simply not further speciate a CoNS isolate, assuming contamination. Unlike other CoNS species, S. lugdunensis is unusually virulent and capable of the spectrum of infection as that of S. aureus. This includes skin and soft tissue, bone, joint, cardiovascular and CNS infections. The toxins typically associated with S. aureus have not been identified; however, various virulence factors are shared that may explain the similar pathogenic potential to S. aureus. S. lugdunensis is more aggressive than other CoNS and despite being sensitive to many antibiotics, carries a high mortality rate in patients with endocarditis compared with other CoNS.[16,20,25] If the clinical situation does not correlate with CoNS, prompt identification to the species level should be performed for identification of S. lugdunensis. Treatment with a -lactam and removal of any infected foreign material should be pursued. For penicillin-allergic patients, vancomycin is an alternative. Based on the virulence of this organism, if S. lugdunensis is isolated, a TEE to evaluate for infective endocarditis should be pursued.

Sidebar
Key Issues

Staphylococcus lugdunensisbehaves likes Staphylococcus aureusand should not be considered a typical coagulase-negative staphylococcus.

Infections may be underdiagnosed owing to identification methods. Cardiovascular infections including native and prosthetic valve endocarditis, pacemaker-related endocarditis and myocarditis have been described.

Endocarditis, secondary to other coagulase-negative staphylococci, tends to be indolent. However, the spectrum of infective endocarditis including valve dehiscence, abscess formation and vegetation with embolic phenomenon is seen with S. lugdunensis.

In the CNS, brain abscess, meningitis and ventriculoperitoneal shunt infections have been observed. Skin and soft-tissue infection, bacteremia, septic shock, toxic shock syndrome, peritonitis, osteomyelitis, prosthetic joint infections and ocular infections have been reported.

Infective endocarditis should be ruled out in patients with S. lugdunensisbacteremia. Obtaining a S. lugdunensisisolate from clinical specimens should prompt an approach similar to the approach considered for etiology, management and treatment of S. aureus.

References

1.

Pfaller MA, Jones RN, Doern GV, Sader HS, Kugler KC, Beach ML. Survey of blood stream infections attributable to Gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group. Diagn. Microbiol. Infect. Dis. 33(4), 283297 (1999).

2.

Jarlov JO, Hojbjerg T, Busch-Sorensen C et al. Coagulase-negative staphylococci in Danish blood cultures: species distribution and antibiotic susceptibility. J. Hosp. Infect. 32(3), 217227 (1996).

3.

Shin JH, Jung HJ, Lee HR, Kim JH, Kim HR, Lee JN. Prevalence, identification, and antimicrobial susceptibility of Staphylococcus lugdunensis from various clinical specimens in Korea. Jpn J. Infect. Dis. 60(5), 312313 (2007).

4.

Choi SH, Chung JW, Lee EJ et al. Incidence, characteristics, and outcomes of Staphylococcus lugdunensis bacteremia. J. Clin. Microbiol. 48(9), 33463349 (2010).

5.

Kawamura Y, Hou XG, Sultana F et al. Distribution of Staphylococcus species among human clinical specimens and emended description of Staphylococcus caprae. J. Clin. Microbiol. 36(7), 20382042 (1998).

6.

De Paulis AN, Predari SC, Chazarreta CD, Santoianni JE. Five-test simple scheme for species-level identification of clinically significant coagulase-negative staphylococci. J. Clin. Microbiol. 41(3), 1219 1224 (2003).

7.

Kleeman KT, Bannerman TL, Kloos WE. Species distribution of coagulase-negative staphylococcal isolates at a community hospital and implications for selection of staphylococcal identification procedures. J. Clin. Microbiol. 31(5), 13181321 (1993).

8.

Kleiner E, Monk AB, Archer GL, Forbes BA. Clinical significance of Staphylococcus lugdunensis isolated from routine cultures. Clin. Infect. Dis. 51(7), 801803 (2010).

9.

Herchline TE, Ayers LW. Occurrence of Staphylococcus lugdunensis in consecutive clinical cultures and relationship of isolation to infection. J. Clin. Microbiol. 29(3), 419421 (1991).

10. Bieber L, Kahlmeter G. Staphylococcus lugdunensis in several niches of the normal skin flora. Clin. Microbiol. Infect. 16(4), 385388 (2010). 11. Freney J. Staphylococcus lugdunensis sp. nov. and Staphylococcus schleiferi sp. nov., two species from human clinical specimens. Int. J. Syst. Bacteriol. 38(2), 168172 (1988). 12. Pirila L, Soderstrom KO, Hietarinta M, Jalava J, Kyto V, Toivanen A. Fatal myocardial necrosis caused by Staphylococcus lugdunensis and cytomegalovirus in a patient with scleroderma. J. Clin. Microbiol. 44(6), 22952297 (2006). 13. Bhanot N, Sahud AG, Bhat S, Lane S, Manyam H, Chan-Tompkins NH. Fever of unknown origin: a case of cardiac myxoma infected with Staphylococcus lugdunensis. South. Med. J. 103(7), 697700 (2010). 14. Patil R, Patil T, Hussain KM. Staphylococcus lugdunensis native tricuspid valve endocarditis: a case report and review of literature. J. Gen. Intern. Med. DOI: 10.1007/s11606-011-1718-5 (2011) (Epub ahead of print). 15. Longauerova A. Coagulase negative staphylococci and their participation in pathogenesis of human infections. Bratisl. Lek. Listy 107(1112), 448452 (2006). 16. Liu PY, Huang YF, Tang CW et al. Staphylococcus lugdunensis infective endocarditis: a literature review and analysis of risk factors. J. Microbiol. Immunol. Infect. 43(6), 478484 (2010). 17. Van Hoovels L, De Munter P, Colaert J et al. Three cases of destructive native valve endocarditis caused by Staphylococcus lugdunensis. Eur. J. Clin. Microbiol. Infect. Dis. 24(2), 149152 (2005). 18. De Hondt G, Ieven M, Vandermersch C, Colaert J. Destructive endocarditis caused by Staphylococcus lugdunensis. Case report and review of the literature. Acta. Clin. Belg. 52(1), 2730 (1997). 19. Koh TW, Brecker SJ, Layton CA. Successful treatment of Staphylococcus lugdunensis endocarditis complicated by multiple emboli: a case report and review of the literature. Int. J. Cardiol. 55(2), 193 197 (1996). 20. Anguera I, Del Rio A, Miro JM et al. Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles. Heart 91(2), e10 (2005). 21. Baddour LM, Bettmann MA, Bolger AF et al. Nonvalvular cardiovascular device-related infections. Clin. Infect. Dis. 38(8), 11281130 (2004).

22. Kamaraju S, Nelson K, Williams DN, Ayenew W, Modi KS. Staphylococcus lugdunensis pulmonary valve endocarditis in a patient on chronic hemodialysis. Am. J. Nephrol. 19(5), 605608 (1999). 23. Matthews PC, Missouris CG, Jordaan J, Lessing MP. Staphylococcus lugdunensis endocarditis following cardiac catheterisation. Int. J. Cardiol. 130(1), 8788 (2008). 24. Polenakovik H, Herchline T, Bacheller C, Bernstein J. Staphylococcus lugdunensis endocarditis after angiography. Mayo Clin. Proc. 75(6), 656657 (2000). 25. Fervenza FC, Contreras GE, Garratt KN, Steckelberg JM. Staphylococcus lugdunensis endocarditis: a complication of vasectomy? Mayo Clin. Proc. 74(12), 12271230 (1999). 26. Patel R, Piper KE, Rouse MS, Uhl JR, Cockerill FR 3rd, Steckelberg JM. Frequency of isolation of Staphylococcus lugdunensis among staphylococcal isolates causing endocarditis: a 20-year experience. J. Clin. Microbiol. 38(11), 42624263 (2000). 27. Kragsbjerg P, Bomfim-Loogna J, Tornqvist E, Soderquist B. Development of antimicrobial resistance in Staphylococcus lugdunensis during treatment-report of a case of bacterial arthritis, vertebral osteomyelitis and infective endocarditis. Clin. Microbiol. Infect. 6(9), 496499 (2000). 28. Karchmer AW, Longworth DL. Infections of intracardiac devices. Cardiol. Clin. 21(2), 253271, vii (2003). 29. Greig JM, Wood MJ. Staphylococcus lugdunensis vertebral osteomyelitis. Clin. Microbiol. Infect. 9(11), 11391141 (2003). 30. Cooke RP, James SE, Sallomi DF. Infective discitis due to Staphylococcus lugdunensis a case of missed opportunity. Br. J. Biomed. Sci. 60(3), 162164 (2003). 31. Guttmann G, Garazi S, Van Linthoudt D. Spondylodiscitis due to Staphylococcus lugdunensis. Clin. Exp. Rheumatol. 18(2), 271272 (2000). 32. Murdoch DR, Everts RJ, Chambers ST, Cowan IA. Vertebral osteomyelitis due to Staphylococcus lugdunensis. J. Clin. Microbiol. 34(4), 993994 (1996). 33. Thomas S, Hoy C, Capper R. Osteomyelitis of the ear canal caused by Staphylococcus lugdunensis. J. Infect. 53(5), e227e229 (2006). 34. Mei-Dan O, Mann G, Steinbacher G, Ballester SJ, Cugat RB, Alvarez PD. Septic arthritis with Staphylococcus lugdunensis following arthroscopic ACL revision with BPTB allograft. Knee Surg. Sports Traumatol. Arthrosc. 16(1), 1518 (2008).

35. Sampathkumar P, Osmon DR, Cockerill FR 3rd. Prosthetic joint infection due to Staphylococcus lugdunensis. Mayo. Clin. Proc. 75(5), 511512 (2000). 36. Weightman NC, Allerton KE, France J. Bone and prosthetic joint infection with Staphylococcus lugdunensis. J. Infect. 40(1), 9899 (2000). 37. Zinkernagel AS, Zinkernagel MS, Elzi MV et al. Significance of Staphylococcus lugdunensis bacteremia: report of 28 cases and review of the literature. Infection 36(4), 314321 (2008). 38. Woznowski M, Quack I, Bolke E et al. Fulminant Staphylococcus lugdunensis septicaemia following a pelvic varicella-zoster virus infection in an immune-deficient patient: a case report. Eur. J. Med. Res. 15(9), 410414 (2010). 39. Castro JG, Dowdy L. Septic shock caused by Staphylococcus lugdunensis. Clin. Infect. Dis. 28(3), 681682 (1999). 40. Pareja J, Gupta K, Koziel H. The toxic shock syndrome and Staphylococcus lugdunensis bacteremia. Ann. Intern. Med. 128(7), 603604 (1998). 41. Fadel HJ, Patel R, Vetter EA, Baddour LM. Clinical significance of a single Staphylococcus lugdunensis-positive blood culture. J. Clin. Microbiol. 49(4), 16971699 (2011). 42. Tan TY, Ng SY, Ng WX. Clinical significance of coagulase-negative staphylococci recovered from nonsterile sites. J. Clin. Microbiol. 44(9), 34133414 (2006). 43. Arias M, Tena D, Apellaniz M et al. Skin and soft tissue infections caused by Staphylococcus lugdunensis: report of 20 cases. Scand. J. Infect. Dis 42(1112), 879884 (2010). 44. Bellamy R, Barkham T. Staphylococcus lugdunensis infection sites: predominance of abscesses in the pelvic girdle region. Clin. Infect. Dis. 35(3), E32E34 (2002). 45. Bocher S, Tonning B, Skov RL, Prag J. Staphylococcus lugdunensis, a common cause of skin and soft tissue infections in the community. J. Clin. Microbiol. 47(4), 946950 (2009). 46. Asnis DS, St John S, Tickoo R, Arora A. Staphylococcus lugdunensis breast abscess: is it real? Clin. Infect. Dis. 36(10), 1348 (2003). 47. Lina B, Vandenesch F, Reverdy ME, Greenland T, Fleurette J, Etienne J. Non-puerperal breast infections due to Staphylococcus lugdunensis. Eur. J. Clin. Microbiol. Infect. Dis. 13(8), 686687 (1994). 48. Matthews PC, Lazarus R, Protheroe A, Milford C, Bowler IC. Acute necrotizing sinusitis caused by Staphylococcus lugdunensis. J. Clin. Microbiol. 49(7), 27402742 (2011).

49. Shaaban HS, Choo HF, Sensakovic JW. A case of Staphylococcus lugdunensis related pyomyoma occurring after cesarean section. J. Glob. Infect. Dis. 3(1), 101102 (2011). 50. Bello C, Eskandar M, El GR, Sobande A, Nour H, Shafiq H. Staphylococcus lugdunensis endometritis: a case report. West Afr. J. Med. 26(3), 243245 (2007). 51. Tamdy A, El Louali F, Ounzar M et al. Multiple mycotic aneurysms reveal Staphylococcus lugdunensis endocarditis in a young patient. Heart Lung 40(4), 352357 (2011). 52. Spanu T, Rigante D, Tamburrini G et al. Ventriculitis due to Staphylococcus lugdunensis: two case reports. J. Med. Case Reports 2, 267 (2008). 53. Elliott SP, Yogev R, Shulman ST. Staphylococcus lugdunensis: an emerging cause of ventriculoperitoneal shunt infections. Pediatr. Neurosurg. 35(3), 128130 (2001). 54. Sandoe JA, Longshaw CM. Ventriculoperitoneal shunt infection caused by Staphylococcus lugdunensis. Clin. Microbiol. Infect. 7(7), 385387 (2001). 55. Fleurette J, Bes M, Brun Y et al. Clinical isolates of Staphylococcus lugdunensis and S. schleiferi: bacteriological characteristics and susceptibility to antimicrobial agents. Res. Microbiol. 140(2), 107 118 (1989). 56. Ludlam H, Phillips I. Staphylococcus lugdunensis peritonitis. Lancet 2(8676), 1394 (1989). 57. Bannerman TL, Rhoden DL, Mcallister SK, Miller JM, Wilson LA. The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis. Arch. Ophthalmol. 115(3), 357361 (1997). 58. Chiquet C, Pechinot A, Creuzot-Garcher C et al. Acute postoperative endophthalmitis caused by Staphylococcus lugdunensis. J. Clin. Microbiol. 45(6), 16731678 (2007). 59. Giese B, Glowinski F, Paprotka K et al. Expression of -toxin by Staphylococcus aureus mediates escape from phago-endosomes of human epithelial and endothelial cells in the presence of -toxin. Cell Microbiol. 13(2), 316329 (2011). 60. Bera A, Biswas R, Herbert S, Gotz F. The presence of peptidoglycan O-acetyltransferase in various staphylococcal species correlates with lysozyme resistance and pathogenicity. Infect. Immun. 74(8), 45984604 (2006). 61. Paulsson M, Petersson AC, Ljungh A. Serum and tissue protein binding and cell surface properties of Staphylococcus lugdunensis. J. Med. Microbiol. 38(2), 96102 (1993).

62. Zhang YQ, Ren SX, Li HL et al. Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228). Mol. Microbiol. 49(6), 15771593 (2003). 63. Von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect. Dis. 2(11), 677685 (2002). 64. Stout RD, Ferguson KP, Li YN, Lambe DW Jr. Staphylococcal exopolysaccharides inhibit lymphocyte proliferative responses by activation of monocyte prostaglandin production. Infect. Immun. 60(3), 922 927 (1992). 65. Grant CE, Sewell DL, Pfaller M, Bumgardner RV, Williams JA. Evaluation of two commercial systems for identification of coagulase-negative staphylococci to species level. Diagn. Microbiol. Infect. Dis 18(1), 15 (1994). 66. Kloos WE, George CG. Identification of Staphylococcus species and subspecies with the MicroScan Pos ID and Rapid Pos ID panel systems. J. Clin. Microbiol. 29(4), 738744 (1991). 67. Mateo M, Maestre JR, Aguilar L et al. Genotypic versus phenotypic characterization, with respect to susceptibility and identification, of 17 clinical isolates of Staphylococcus lugdunensis. J. Antimicrob. Chemother. 56(2), 287291 (2005). 68. Carroll KC, Weinstein MP. Manual of Clinical Microbiology. ASM Press, Washington DC, USA (2007). 69. Leung MJ, Nuttall N, Pryce TM, Coombs GW, Pearman JW. Colony variation in Staphylococcus lugdunensis. J. Clin. Microbiol. 36(10), 30963098 (1998). 70. Fadel HJ, Patel R, Vetter EA, Baddour LM. The clinical significance of a single positive blood culture for Staphylococcus lugdunensis. J. Clin. Microbiol. 49(4), 16971699 (2011). 71. Pinsky BA, Samson D, Ghafghaichi L, Baron EJ, Banaei N. Comparison of real-time PCR and conventional biochemical methods for identification of Staphylococcus lugdunensis. J. Clin. Microbiol. 47(11), 34723477 (2009). 72. Arciola CR, Campoccia D, An YH et al. Prevalence and antibiotic resistance of 15 minor staphylococcal species colonizing orthopedic implants. Int. J. Artif. Organs 29(4), 395401 (2006). 73. Vandenesch F, Etienne J, Reverdy ME, Eykyn SJ. Endocarditis due to Staphylococcus lugdunensis: report of 11 cases and review. Clin. Infect. Dis. 17(5), 871876 (1993). 74. Higaki S, Kitagawa T, Morohashi M, Yamagishi T. Distribution and antimicrobial susceptibility of coagulase-negative staphylococci from skin lesions. J. Int. Med. Res. 27(4), 191195 (1999).

75. Goldstein EJ, Citron DM, Merriam CV, Warren YA, Tyrrell KL, Fernandez HT. In vitro activity of ceftobiprole against aerobic and anaerobic strains isolated from diabetic foot infections. Antimicrob. Agents Chemother. 50(11), 39593962 (2006). 76. Woods W, Ramotar K, Lem P, Toye B. Oxacillin susceptibility testing of coagulase-negative staphylococci using the disk diffusion method and the Vitek GPS-105 card( small star, filled). Diagn. Microbiol. Infect. Dis 42(4), 291294 (2002). 77. Van Der Mee-Marquet N, Achard A, Mereghetti L, Danton A, Minier M, Quentin R. Staphylococcus lugdunensis infections: high frequency of inguinal area carriage. J. Clin. Microbiol. 41(4), 14041409 (2003). 78. Hellbacher C, Tornqvist E, Soderquist B. Staphylococcus lugdunensis: clinical spectrum, antibiotic susceptibility, and phenotypic and genotypic patterns of 39 isolates. Clin. Microbiol. Infect. 12(1), 43 49 (2006). 79. Frank KL, Reichert EJ, Piper KE, Patel R. In vitro effects of antimicrobial agents on planktonic and biofilm forms of Staphylococcus lugdunensis clinical isolates. Antimicrob. Agents Chemother. 51(3), 888895 (2007). 80. Tee W. Staphylococcus lugdunensis carrying the mecA gene causes catheter-associated bloodstream infection in premature neonate. J. Clin. Microbiol. 41(1), 519520 (2003). 81. Becker K, Pagnier I, Schuhen B et al. Does nasal cocolonization by methicillin-resistant coagulasenegative staphylococci and methicillin-susceptible Staphylococcus aureus strains occur frequently enough to represent a risk of false-positive methicillin-resistant S. aureus determinations by molecular methods? J. Clin. Microbiol. 44(1), 229231 (2006). 82. Pereira EM, Schuenck RP, Nouer SA, Santos KR. Methicillin-resistant Staphylococcus lugdunensis carrying SCCmec type V misidentified as MRSA. Braz. J. Infect. Dis. 15(3), 293295 (2011). 83. Kawaguchi E, Minamide W, Mori H, Igimi H. [The taxonomic distribution, characteristic and susceptibility against antimicrobial agents of methicillin-resistant staphylococci isolated from blood]. Kansenshogaku Zasshi 70(11), 11471153 (1996). 84. Wu AB, Wang MC, Tseng CC et al. Clinical and microbiological characteristics of community-acquired Staphylococcus lugdunensis infections in Southern Taiwan. J. Clin. Microbiol. 49(8), 30153018 (2011). 85. Kotsakis SD, Tzouvelekis LS, Zerva L, Liakopoulos A, Petinaki E. Staphylococcus lugdunensis strain with a modified PBP1A/1B expressing resistance to -lactams. Eur. J. Clin. Microbiol. Infect. Dis. DOI: 10.1007/s10096-011-1289-8 (2011) (Epub ahead of print).

86. Wilson W, Taubert KA, Gewitz M et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 116(15), 1736 1754 (2007). 87. Mendes RE, Sader HS, Jones RN. Activity of telavancin and comparator antimicrobial agents tested against Staphylococcus spp. isolated from hospitalised patients in Europe (20072008). Int. J. Antimicrob. Agents 36(4), 374379 (2010). 88. Merino P, Arribi A, Gestoso I, Picazo J, Gimeno L, Del Potro E. Linezolid treatment of a prosthetic joint infection with Staphylococcus lugdunensis in a patient with multiple myeloma. Int. J. Antimicrob. Agents 35(2), 203204 (2010). 89. 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 111(23), e394e434 (2005). Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. Expert Rev Anti Infect Ther. 2011;9(10):901-907. 2011 Expert Reviews Ltd.