Skip to main content Accessibility help


  • Access
  • Cited by 28


      • Send article to Kindle

        To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Staphylococcal cassette chromosome mec (SCCmec) in methicillin-resistant coagulase-negative staphylococci. A review and the experience in a tertiary-care setting
        Available formats

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Staphylococcal cassette chromosome mec (SCCmec) in methicillin-resistant coagulase-negative staphylococci. A review and the experience in a tertiary-care setting
        Available formats

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Staphylococcal cassette chromosome mec (SCCmec) in methicillin-resistant coagulase-negative staphylococci. A review and the experience in a tertiary-care setting
        Available formats
Export citation


Coagulase-negative staphylococci (CNS) are increasingly recognized to cause clinically significant infections, with S. epidermidis often cited as the third most common cause of nosocomial sepsis. Among CNS, there is a high prevalence of methicillin resistance associated with staphylococcal cassette chromosome (SCCmec) elements. Although identical SCCmec types can exist in S. aureus and CNS, some novel classes of SCCmec may be unique to CNS. Differences in the accuracy of identification of CNS species and use of non-standardized methods for the detection of methicillin resistance have led to confusing data in the literature. In addition to the review of SCCmec in CNS, in this paper we report a 2-year surveillance of methicillin-resistant CNS in a tertiary-care hospital in Guadalajara, Mexico.

Clinical importance of coagulase-negative staphylococci (CNS)

CNS are differentiated from the closely related but more virulent Staphylococcus aureus by their inability to produce free coagulase enzyme [1]. There are currently more than 40 recognized species in the group [2], many of which form part of the normal flora of healthy human skin and mucus membranes; those most frequently associated with infections in humans are S. epidermidis, S. haemolyticus and S. saprophyticus. Other species occasionally isolated from clinical specimens include S. hominis, S. warneri, S. capitis, S. simulans, S. cohnii, S. xylosus, S. saccharolyticus and S. lugdunensis [35].

Within the last few years, CNS have been increasingly recognized to cause clinically significant infections and are particularly associated with the use of medical devices such as intravascular and peritoneal dialysis catheters, cerebrospinal fluid shunts, prosthetic heart valves, and other plastic indwelling devices. Most infections result from the inoculation of organisms on the skin at the time of device implantation in the hospital [35]. The ability to infect patients carrying medical devices is primarily related to the capacity of some CNS to form biofilms where the bacteria adhere to the inert surface of the plastic devices, triggering a change in microbial behaviour such as by quorum sensing, in which the outer layer of cells protect the interior community [6] and confer increased resistance to antimicrobial agents [7].

S. epidermidis is the most commonly isolated CNS and was first identified in microbiological cultures in 1880. In contrast to S. aureus, which is often a cause of serious and fatal infections, S. epidermidis has a predisposition to cause chronic and recurring infections [3, 4, 8, 9]. The identification of this species as an aetiological agent of infection is sometimes difficult as most infections associated with it are characterized by non-specific clinical manifestations and as part of the normal skin flora it is frequently found as a contaminant in cultures. Nevertheless, S. epidermidis is today recognized as an important cause of nosocomial infections and has been ranked the third most common cause of nosocomial sepsis in some studies [10, 11].

The second most commonly isolated species of CNS, S. haemolyticus is part of the resident flora in the axilla, perineum, and inguinal areas of humans. It is sometimes a cause of sepsis and has been repeatedly implicated in bloodstream infections, peritonitis, and infections of the urinary tract, wounds, bone, and joints [10, 11]. Most strains of S. haemolyticus exhibit a highly antibiotic-resistant phenotype [12].

Methicillin resistance and SCCmec

Methicillin-resistant S. aureus (MRSA) isolates were first reported in 1961 [13], and by the mid-1980s it was recognized as a significant problem in the USA, with several outbreaks documented in tertiary-care teaching hospitals [14, 15]. Today, MRSA strains are widespread in all parts of the world and represent a serious burden of infection in many countries, not only in hospitals but also in the wider community. Intrinsic methicillin resistance in staphylococci is due to the expression of a modified penicillin-binding protein PBP2a (PBP2′) encoded by the mecA gene and located on the mobile element staphylococcal cassette chromosome (SCCmec), a genomic island of variable size (range 21–67 kb) [16] integrated at the 3′ end of the orfX [17] gene located near the chromosomal origin of replication. For S. aureus, the element includes the repressor genes mec1 and mecR1 [1821].

Eight different SCCmec types (I–VIII) have been identified and are classified according to different sets of ccr (chromosome cassette recombinase) (ccrAB1, ccrAB2, ccrAB3, ccrAB4, ccrC), which are genes that are responsible for both its chromosomal integration and excision [16, 22]. Several SCCmec subtypes IIA–E [23], IVa–g [2426], and SCC non-mec types have been reported [2731]. In addition, differences in the mec gene complex (classes A–E) [27, 3235] have been described. It should be noted that the majority of the work on the characterization of mecA and its vector, SCC, has centred on MRSA, but this element is not exclusive to S. aureus as it has been found in other species of the genus.

The prevalence of methicillin resistance has been reported to be higher in CNS than in S. aureus, with rates ranging globally from 75% to 90% during the 1990s [12]. S. epidermidis is the most frequently isolated of the methicillin-resistant (MR)-CNS [3640], which mirrors the frequency of both methicillin susceptible and resistant isolates in CNS species. Among human isolates, SCCmec has been described in S. epidermidis, S. haemolyticus, S. hominis, S. capitis, S. sciuri, S. warneri, and S. saprophyticus [3645] (Table 1).

Table 1. Distribution of SCCmec types found in coagulase-negative staphylococci, both in animals and in humans

NT, Non-typable; SCCmec types in parentheses amplified for both elements.

It soon became evident that novel classes of the SCCmec element may exist in CNS as many reports described strains lacking the elements present in S. aureus or reported strains that amplified two elements, suggesting the presence of different elements of SCCmec [36, 37, 39, 40]. As reported for MRSA, high levels of resistance to oxacillin or cefoxitin were linked to the presence of SCCmec type III in CNS [36, 37]. Nevertheless, additionally to SCCmec type III, other types and subtypes have been described for CNS. For example, for S. epidermidis, types I, II (subtypes a, b), III, IV, (subtypes a, b, c, d) and V have been described as well as other putative different SCCmec elements characterized by amplification for two elements: for I and III, for III and IV, for II and V, and for III and V (Table 1).

For S. haemolyticus SCCmec types I, II, III, IV, V and, as described for S. epidermidis, new proposed elements (III variant, amplification for II and V). Additionally to S. epidermidis and S. haemolyticus, SCCmec types have been described for S. warneri, S. lentus, S. sciuri, S. xylosus, S. saprophyticus, S. hominis and S. capitis (Table 1).

MR-CNS in animals

MR-CNS has been reported in several species of animals, such as cattle, sheep, goat, pigs, chickens, dogs, cats, horses and Cope's grey treefrogs where a prevalence as high as 59% has been found [4650]. In several of these studies, some SCCmec elements have been reported (Table 1). It has been suggested that the diversity of CNS species and the SCCmec elements found in isolates from several species of animals, some of them domestic or so-called food animals, and the demonstrated capacity of these bacterial species to cause suppurative disease in these animals (which undoubtedly increases the shed of microorganisms) render them a potential threat to humans and constitutes a potential risk from the consumption of foods of animal origin [51, 52].

Clonal diversity of MR-CNS

The classification of CNS in relation to the SCCmec elements has been achieved primarily by the use of the same strategies used for MRSA. However, as CNS can harbour SCCmec elements different from those in MRSA, the high diversity of these mobile elements poses a significant challenge for researchers. CNS are highly clonally diverse, the most noteworthy example being S. epidermidis, in which a high degree of genetic diversity has been described for the SCCmec element IVa [38]. Moreover, epidemiological studies using multilocus sequence typing (MLST) suggest that S. epidermidis isolates prevalent in the hospital environment differ from those causing community-acquired disease [53]. Lancastre et al. proposed that S. epidermidis clones could be defined by the combination of a carefully standardized pulsed-field gel electrophoresis (PFGE) protocol and identification of the SCCmec type [54].

Another study analysed representative isolates of S. epidermidis from diverse geographic and clinical origins, characterized by SCCmec and MLST, and reported the finding that nine epidemic clonal lineages are disseminated worldwide with one single clonal lineage comprising 74% of the isolates. They concluded that S. epidermidis has a population with an epidemic structure, in which clones have emerged as a result of high levels of recombination and evolved through the transfer of genetic mobile elements, including SCCmec [55].

Origin of methicillin resistance

Evidence suggests that acquisition of SCCmec elements in S. aureus by susceptible ancestors has taken place at different times and at different locations. The first MRSA strain emerged when a SCCmec element was integrated into the chromosome of a susceptible S. aureus strain, but the donor remains unidentified. The mechanisms may involve the action of recombinases, which are capable of striking and incorporating the element into the bacterial chromosome [16]. Although the mec origin remains unknown, it has been suggested that SCCmec can shift between both coagulase-positive and coagulase-negative staphylococci and mecA-positive CNS may act as potential SCCmec donors accounting for the rise in new MRSA clones [56, 57].

In general, CNS are thought to comprise a reservoir of resistance genes for S. aureus and some features that support this hypothesis are:

  1. (i) the higher frequency of SCCmec elements in CNS than in S. aureus;

  2. (ii) the evidenced horizontal transfer of resistance genes from CNS to S. aureus [5864];

  3. (iii) genome flexibility in S. epidermidis which may lead to the acquisition of some transferable resistance elements [65];

  4. (iv) the species-independent conservation of some ccr elements [66];

  5. (v) CNS are more likely to contain different ccr complexes [66];

  6. (vi) the great diversity of SCC elements found in CNS (Table 1),

  7. (vii) the high variation in the prevalence of MRSA according to geographic region and the high prevalence of MR-CNS regardless of the geographic area [12].

New SCCmec types or elements are being continuously discovered around the world in different species and it will be necessary to determine if these diverse elements have been present for a long time or if new clones continue to arise in a microevolutionary process.

Detection of methicillin resistance

Detection of methicillin resistance in CNS is problematic, as expression of the mec gene is heterotypic, being constitutive in many strains, whereas in others it is inducible. Phenotypic methods have been used to detect MR-CNS because they can be readily performed in most laboratories. According to the Clinical and Laboratory Standards Institute (CLSI), the cefoxitin diffusion disk is the preferred method for detection of mecA-mediated resistance in CNS (except for S. lugdunensis); cefoxitin is used as a surrogate for detection of oxacillin resistance [67]. When compared to the molecular detection of methicillin resistance, the sensitivity and specificity of the phenotypic tests for cefoxitin disk diffusion is 94·9% and 97%, respectively, with detection of resistance dependent on species [68].

The performance of the automated Vitek 2 system for identifying mecA-positive staphylococci was comparable to PCR and the CLSI disk diffusion method (sensitivity and specificity of 94·6% and 93·5%, respectively). However, its performance was species dependent as results were poor in tests with S. cohnii, S. hominis and S. saprophyticus [68].

Identification of CNS

Several commercial kits have been used in diagnostic laboratories with varying success for the identification of CNS species including API Staph ID 32 and Vitek 2 (bioMérieux, France); Staph-Zym test (Rosco, Denmark); Staphylo LA test (Wako, Japan); Sensititre (TEK Diagnostic Systems Inc., USA); MicroScan (Dade Behring, USA); Phoenix and Crystal GP systems (Becton Dickinson, USA). The sensitivity of these systems is often not better than fair, particularly for species other than S. epidermidis and S. haemolyticus. For example, MicroScan, Vitek 2, and Crystal GP correctly identified 82·5%, 87·5% and 67·5% of CNS, respectively in human clinical isolates in which S. epidermidis and S. haemolyticus predominated [69]. Furthermore, the new low-inoculum mode of the Phoenix system correctly identified 90·5% of isolates and accuracy was satisfactory for S. epidermidis, S. saprophyticus and S. haemolyticus, but was notably lower for other species such as S. hominis (69·6%) [70]. In general, for most kit systems a lower sensitivity has been reported for the identification of CNS species when S. epidermidis and S. haemolyticus are infrequent in the sample. For example, API Staph ID 32 correctly identified 41% of the CNS isolates from veterinary sources and showed complete (100%) sensitivity for S. epidermidis, but lower values were observed for S. xylosus (87%), S. chromogenes (37%) and S. warneri (15%) [71]. It should be noted that the prevalence and diversity of the SCCmec in CNS has been studied mainly by the use of phenotypic systems, mainly by API ID 32 Staph (Table 2). The results obtained using such systems should be interpreted with caution in the light of the sometimes low specificity for species other than S. epidermidis and S. haemolyticus. As a result many laboratories are increasingly relying on DNA sequencing for species identification [72], while for identification of CNS species, sequence data of housekeeping genes such as rpoB [73, 74], hsp60 [75], dnaJ [76], tuf [77], sodA [78] and 16S RNAr [79] is recommended.

Table 2. Distribution of identification of coagulase-negative staphylococci species and the method used for identification

NT, Non-typable.

Two-year surveillance of MR-CNS in a tertiary-care hospital in Guadalajara, Mexico

To determine the distribution of the SCCmec in MR-CNS and its relation to antimicrobial resistance in a tertiary-care hospital in Guadalajara, Mexico, we studied all the MR-CNS collected from blood samples in 2007 and 2008 (n=45). CNS isolates were identified by conventional biochemical tests [1] and via the use of API strips. Resistance to methicillin was determined for all isolates by the cefoxitin disk test [67] and by PCR [80]. MR-CNS with uncertain biochemical patterns, including species other than S. epidermidis and S. haemolyticus were further examined by amplification and sequencing of the 16S rRNA gene using primers F-5′-GGIACTGAGACACIGICCIIACTCCT-3′ and R-5′-TTCCIITACIGITACCTTGTTACGACTT-3′ [81].

All sequencing was performed at the Instituto de Biotecnología de la Universidad Nacional Autónoma de México.

Preparation of template DNA and SCCmec, ccr and mec class typing were performed as previously described [80] and susceptibility testing was performed by broth microdilution using panels from Sensititre (TEK Diagnostic Systems Inc.) according to the manufacturer's instructions. For all assays, the control organism (S. aureus ATCC 29213) was used and susceptibility breakpoints were as recommended by CLSI [67].

As expected, the most frequently identified MR-CNS species was S. epidermidis (n=34) followed by S. haemolyticus (n=7) and S. hominis (n=4) (Table 3).

Table 3. Distribution of SSCmec cassettes among methicillin-resistant isolates from bloodstream infections within a 2-year period and minimal inhibitory concentrations (MIC) of antimicrobials (μg/ml)

AMC, Amoxicillin-clavulanic acid; Cfp, cefepime; Cxm, cefuroxime; Mer, meropenem; Imp, imipenem; Clin, clindamycin; Cip, ciprofloxacin; Nor, norfloxacin; Nit, nitrofurantoin; Sxt, trimethoprim–sulfamexazole; Clo, chloramphenicol; Rif, rifampicin; Tet, tetracycline; NT, non-typable.

All isolates had a MIC of ⩽4 for teicoplanin, ⩽2 for vancomycin, >32 for cefotaxime, >4 for erythromycin and >16 for cephalothin.

Of the methicillin-resistant S. epidermidis isolates examined, 11-harboured SCCmec type III, 12 SCCmec type IVa, three showed amplification products for II and V elements and one strain was positive for both V and III SCCmec elements. Seven strains were non-typable (Table 3).

Among the S. haemolyticus isolates, type III element was detected in two isolates and two others amplified both types II and V. For S. hominis, one strain typed for the III SCCmec element and three others were non-typable. Multiple ccr elements were found in all three species. MRSA clinical isolates that had been previously characterized in this hospital were SCCmec type II [82]. Interestingly, the SCCmec type II alone was not detected among MR-CNS strains. It should be noted that the MRSA study represented clinical isolates collected from 1999 to 2003.

An extremely high level of drug resistance was found for all isolates (Table 3). Lower resistance rates were observed for cefuroxime, gentamicin, nitrofurantoin and rifampicin; regardless of the SCCmec detected (the difference was not statistically significant).


The mechanisms contributing to clonal diversification of MR-CNS remain unidentified. Most available information at the present time has been obtained using the tools designed mainly for MRSA and therefore, new CNS specific strategies are needed for the study of clonal diversity of MR-CNS, the SCCmec structure and its potential transmission to S. aureus. Although scientific evidence supports horizontal transfer of mecA, the shift mechanism has yet to be discovered. Finally, because of the increasing variety of CNS species associated with disease in humans, misidentification can lead to false conclusions in epidemiological studies, particularly in species other than S. epidermidis and S. haemolyticus.


We thank Maria de la Luz Acevedo and Carlos Paz for their technical assistance and Dr Sergio Lozano for reviewing the manuscript.




1.Bannerman, TL, Peacock, SJ. Staphylococcus, Micrococcus and other catalase positive cocci. In: Murray, PR, Baron, EJ, Jorgensen, JH, Pfaller, MA, Landry, ML, eds. Manual of Clinical Microbiology, 9th edn. Washington, DC: ASM Press, 2007, pp. 390404.
2.Euzeby, JP. List of Bacterial Names with Standing in Nomenclature: a folder available on the Internet. International Journal of Systematic Bacteriology 1997; 47: 590592.
3.Rogers, KL, Fey, PD, Rupp, ME. Coagulase-negative staphylococcal infections. Infection Disease Clinics of North America 2009; 23: 7398.
4.Huebner, J, Goldmann, DA. Coagulase-negative staphylococci: role as pathogens. Annual Review of Medicine 1999; 50: 223236.
5.McCann, MT, Gilmore, BF, Gorman, SP. Staphylococcus epidermidis device-related infections: pathogenesis and clinical management. Journal of Pharmacy and Pharmacology 2008; 60: 15511571.
6.Davey, ME, O'Toole, GA. Microbial biofilms: from ecology to molecular genetics. Microbiology and Molecular Biology Reviews 2000; 64: 847867.
7.Stewart, P, Costerton, J. Antibiotic resistance of bacteria in biofilms. Lancet 2001; 58: 135138.
8.Gill, SR, et al. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. Journal of Bacteriology 2005; 187: 24262438.
9.von Eiff, C, Peters, G, Heilmann, C. Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infectious Diseases 2002; 2: 677685.
10.Pfaller, MA, et al. 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. Diagnostic Microbiology and Infectious Disease 1999; 33: 283297.
11.Emory, TG, Gaynes, RP. An overview of nosocomial infections, including the role of the microbiology laboratory. Clinical Microbiology Reviews 1993; 6: 428442.
12.Diekema, DJ, 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. Clinical Infectious Diseases 2001; 32 (Suppl. 2): S11432.
13.Barber, M. Methicillin-resistant staphylococci. Journal of Clinical Pathology 1961; 14: 385393.
14.Archer, GL, Mayhall, CG. Comparison of epidemiological markers used in the investigation of an outbreak of methicillin-resistant Staphylococcus aureus infections. Journal of Clinical Microbiology 1983; 18: 395399.
15.Rhinehart, E, et al. G. Nosocomial clonal dissemination of methicillin-resistant Staphylococcus aureus. Elucidation by plasmid analysis. Archives of Internal Medicine 1987; 147: 521524.
16.Katayama, Y, Ito, T, Hiramatsu, K. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2000; 44: 15491555.
17.Ito, T, Katayama, Y, Hiramatsu, K. Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrobial Agents and Chemotherapy 1999; 43: 14491458.
18.Katayama, Y, Ito, T, Hiramatsu, K. Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains: role of IS431-mediated mecI deletion in expression of resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus. Antimicrobial Agents and Chemotherapy 2001; 45: 19551963.
19.Kobayashi, N, Alam, MM, Urasawa, S. Genomic rearrangement of the mec regulator region mediated by insertion of IS431 in methicillin-resistant staphylococci. Antimicrobial Agents and Chemotherapy 2001; 45: 335338.
20.Kobayashi, N, et al. Distribution of insertion sequence-like element IS1272 and its position relative to methicillin resistance genes in clinically important staphylococci. Antimicrobial Agents and Chemotherapy 1999; 43: 27802782.
21.Suzuki, E, et al. Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains. Antimicrobial Agents and Chemotherapy 1993; 37: 12191226.
22.Zhang, K, et al. Novel staphylococcal cassette chromosome mec type, tentatively designated type VIII, harboring class A mec and type 4 ccr gene complexes in a Canadian epidemic strain of methicillin-resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2009; 53: 531540.
23.Shore, A, et al. Seven novel variants of the staphylococcal chromosomal cassette mec in methicillin-resistant Staphylococcus aureus isolates from Ireland. Antimicrobial Agents and Chemotherapy 2005; 49: 20702083.
24.Ito, T, et al. Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug Resistance Updates 2003; 6: 4152.
25.Kwon, N, et al. Staphylococcal cassette chromosome mec (SCCmec) characterization and molecular analysis for methicillin-resistant Staphylococcus aureus and novel SCCmec subtype IVg isolated from bovine milk in Korea. Journal of Antimicrobial Chemotherapy 2005; 56: 624632.
26.Ma, XX, et al. Novel type of staphylococcal cassette chromosome mec identified in community-acquired methicillin-resistant Staphylococcus aureus strains. Antimicrobial Agents and Chemotherapy 2002; 46: 11471152.
27.Ito, T, et al. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2001; 45: 13231336.
28.Katayama, Y, et al. Identification in methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec of methicillin-resistant Staphylococcus aureus. Journal of Bacteriology 2003; 185: 27112722.
29.Katayama, Y, et al. Jumping the barrier to beta-lactam resistance in Staphylococcus aureus. Journal of Bacteriology 2003; 185: 54655472.
30.Luong, TT, et al. Type 1 capsule genes of Staphylococcus aureus are carried in a staphylococcal cassette chromosome genetic element. Journal of Bacteriology 2002; 184: 36233629.
31.Mongkolrattanothai, K, et al. Novel non-mecA-containing staphylococcal chromosomal cassette composite island containing pbp4 and tagF genes in a commensal staphylococcal species: a possible reservoir for antibiotic resistance islands in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2004; 48: 18231836.
32.Chongtrakool, P, et al. Staphylococcal cassette chromosome mec (SCCmec) typing of methicillin-resistant Staphylococcus aureus strains isolated in 11 Asian countries: a proposal for a new nomenclature for SCCmec elements. Antimicrobial Agents and Chemotherapy 2006; 50: 10011012.
33.Hiramatsu, K, et al. The emergence and evolution of methicillin-resistant Staphylococcus aureus. Trends in Microbiology 2001; 9: 486493.
34.Ito, T, et al. Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC. Antimicrobial Agents and Chemotherapy 2004; 48: 26372651.
35.Okuma, K, et al. Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. Journal of Clinical Microbiology 2002; 40: 42894294.
36.Machado, AB, et al. Distribution of staphylococcal cassette chromosome mec (SCCmec) types I, II, III and IV in coagulase-negative staphylococci from patients attending a tertiary hospital in southern Brazil. Journal of Medical Microbiology 2007; 56: 13281333.
37.Ruppé, E, et al. Diversity of staphylococcal cassette chromosome mec structures in methicillin-resistant Staphylococcus epidermidis and Staphylococcus haemolyticus strains among outpatients from four countries. Antimicrobial Agents and Chemotherapy 2009; 53: 442449.
38.Jamaluddin, TZ, et al. Extreme genetic diversity of methicillin-resistant Staphylococcus epidermidis strains disseminated among healthy Japanese children. Journal of Clinical Microbiology 2008; 46: 37783783.
39.Ibrahem, S, et al. Carriage of methicillin-resistant staphylococci and their SCCmec types in a long-term-care facility. Journal of Clinical Microbiology 2009; 47: 3237.
40.Hanssen, AM, Kjeldsen, G, Sollid, JU. Local variants of staphylococcal cassette chromosome mec in sporadic methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci: evidence of horizontal gene transfer? Antimicrobial Agents and Chemotherapy 2004; 48: 285296.
41.Wisplinghoff, H, et al. Related clones containing SCCmec type IV predominate among clinically significant Staphylococcus epidermidis isolates. Antimicrobial agents and Chemotherapy 2003; 47: 35743579.
42.Pi, B, et al. Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates. Journal of Medical Microbiology 2009; 58(Pt 6): 731736.
43.Li, M, et al. Molecular characterization of Staphylococcus epidermidis strains isolated from a teaching hospital in Shanghai, China. Journal of Medical Microbiology 2009; 58: 456461.
44.Söderquist, B, Berglund, C. Methicillin-resistant Staphylococcus saprophyticus in Sweden carries various types of staphylococcal cassette chromosome mec (SCCmec). Clinical Microbiology Infection (in press).
45.Higashide, M, et al. Methicillin-resistant Staphylococcus saprophyticus isolates carrying staphylococcal cassette chromosome mec have emerged in urogenital tract infections. Antimicrobial Agents and Chemotherapy 2008; 52: 20612068.
46.Yasuda, R, et al. Methicillin-resistant coagulase-negative staphylococci isolated from healthy horses in Japan. American Journal of Veterinary Research 2000; 61: 14511455.
47.Malik, S, et al. Molecular typing of methicillin-resistant staphylococci isolated from cats and dogs. Journal of Antimicrobial Chemotherapy 2006; 58: 428431.
48.Zhang, Y, Agidi, S, Lejeune, JT. Diversity of staphylococcal cassette chromosome in coagulase-negative staphylococci from animal sources. Journal of Applied Microbiology 2009; 107: 1375–83.
49.van Duijkeren, E, et al. Methicillin-resistant staphylococci isolated from animals. Veterinary Microbiology 2004; 103: 9197.
50.Slaughter, DM, et al. Antibiotic resistance in coagulase-negative staphylococci isolated from Cope's gray treefrogs (Hyla chrysoscelis). FEMS Microbiology Letters 2001; 205: 265270.
51.Lee, JH. Methicillin (Oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans. Applied and Environmental Microbiology 2003; 69: 64896494.
52.Burriel, AR. Resistance of coagulase-negative staphylococci isolated from sheep to various antimicrobial agents. Research in Veterinary Science 1997; 63: 189190.
53.Ziebuhr, W, et al. Nosocomial infections by Staphylococcus epidermidis: how a commensal bacterium turns into a pathogen. International Journal of Antimicrobial Agents 2006; 28 (Suppl. 1): S14S20.
54.Miragaia, M, et al. Comparison of molecular typing methods for characterization of Staphylococcus epidermidis: proposal for clone definition. Journal of Clinical Microbiology 2008; 46: 118129.
55.Miragaia, M, et al. Inferring a population structure for Staphylococcus epidermidis from multilocus sequence typing data. Journal of Bacteriology 2007; 189: 25402552.
56.Musser, JM, Kapur, V. Clonal analysis of methicillin-resistant Staphylococcus aureus strains from intercontinental sources: association of the mec gene with divergent phylogenetic lineages implies dissemination by horizontal transfer and recombination. Journal of Clinical Microbiology 1992; 30: 20582063.
57.Hanssen, AM, Ericson Sollid, JU. SCCmec in staphylococci: genes on the move. FEMS Immunology and Medical Microbiology 2006; 46: 820.
58.Archer, GL, Scott, J. Conjugative transfer genes in staphylococcal isolates from the United States. Antimicrobial Agents and Chemotherapy 1991; 35: 25002504.
59.Forbes, BA, Schaberg, DR. Transfer of resistance plasmids from Staphylococcus epidermidis to Staphylococcus aureus: evidence for conjugative exchange of resistance. Journal of Bacteriology 1983; 153: 627634.
60.Hurdle, JG, et al. In vivo transfer of high-level mupirocin resistance from Staphylococcus epidermidis to methicillin-resistant Staphylococcus aureus associated with failure of mupirocin prophylaxis. Journal of Antimicrobial Chemotherapy 2005; 56: 11661168.
61.Townsend, DE, et al. Conjugative, staphylococcal plasmids carrying hitch-hiking transposons similar to Tn554: intra- and interspecies dissemination of erythromycin resistance. Australian Journal of Experimental Biology and Medical Science 1986; 64: 367379.
62.Udo, EE, Jacob, LE, Mokadas, EM. Conjugative transfer of high-level mupirocin resistance from Staphylococcus haemolyticus to other staphylococci. Antimicrobial Agents and Chemotherapy 1997; 41: 693695.
63.Wielders, CL, et al. In-vivo transfer of mecA DNA to Staphylococcus aureus. Lancet 2001; 357: 16741675.
64.Berglund, C, Söderquist, B. The origin of a methicillin-resistant Staphylococcus aureus isolate at a neonatal ward in Sweden-possible horizontal transfer of a staphylococcal cassette chromosome mec between methicillin-resistant Staphylococcus haemolyticus and Staphylococcus aureus. Clinical Microbiology and Infection 2008; 14: 10481056.
65.Kozitskaya, S, et al. The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides. Infection and Immunity 2004; 72: 12101215.
66.Hanssen, AM, Sollid, JU. Multiple staphylococcal cassette chromosomes and allelic variants of cassette chromosome recombinases in Staphylococcus aureus and coagulase-negative staphylococci from Norway. Antimicrobial Agents and Chemotherapy 2007; 51: 16711677.
67.Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Eighth Informational Supplement, CLSI document M100-S19. Wayne, PA: Clinical and Laboratory Standards Institute, 2009.
68.John, MA, et al. Comparison of three phenotypic techniques for detection of methicillin resistance in Staphylococcus spp. reveals a species-dependent performance. Journal of Antimicrobial Chemotherapy 2009; 63: 493496.
69.Kim, M, et al. Comparison of the MicroScan, VITEK 2, and Crystal GP with 16S rRNA sequencing and MicroSeq 500 v2.0 analysis for coagulase-negative staphylococci. BMC Microbiology 2008; 8: 233.
70.Brigante, G, et al. Identification of coagulase-negative staphylococci by using the BD phoenix system in the low-inoculum mode. Journal of Clinical Microbiology 2008; 46: 38263828.
71.Sampimon, OC, et al. Performance of API Staph ID 32 and Staph-Zym for identification of coagulase-negative staphylococci isolated from bovine milk samples. Veterinary Microbiology 2009; 136: 300305.
72.Clinical Laboratory Standards Institute. Interpretive criteria for microorganism identification by DNA target sequencing; proposed guideline. In: CLSI document MM18-P, Wayne, PA, 2007.
73.Drancourt, M, Raoult, D. rpoB-gene sequence-based identification of Staphylococcus species. Journal of Clinical Microbiology 2002; 40: 13331338.
74.Mellmann, A, et al. Sequencing and staphylococci identification. Emerging Infectious Diseases 2006; 12: 333336.
75.Kwok, AY, et al. Species identification and phylogenetic relationships based on partial HSP60 gene sequences within the genus Staphylococcus. International Journal of Systematic Bacteriology 1999; 49: 11811192.
76.Shah, MM, et al. dnaJ gene sequence-based assay for species identification and phylogenetic grouping in the genus Staphylococcus. International Journal of Systematic and Evolutionary Microbiology 2007; 57: 2530.
77.Capurro, A, et al. Comparison of commercialized phenotyping system, antimicrobial susceptibility testing, and tuf gene sequencebased genotyping for species-level identification of coagulase-negative staphylococci isolated from cases of bovine mastitis. Veterinary Microbiology 2009; 134: 327333.
78.Poyart, C, et al. Rapid and accurate species-level identification of coagulase-negative staphylococci by using the sodA gene as a target. Journal of Clinical Microbiology 2001; 39: 42964301.
79.Becker, K, et al. Development and evaluation of a quality-controlled ribosomal sequence database for 16S ribosomal DNA-based identification of Staphylococcus species. Journal of Clinical Microbiology 2004; 42: 49884995.
80.Zhang, K, et al. Novel multiplex PCR assay for characterization and concomitant subtyping of staphylococcal cassette chromosome mec types I to V in methicillin-resistant Staphylococcus aureus. Journal of Clinical Microbiology 2005; 43: 50265033.
81.Pei, Z, et al. Bacterial biota in the human distal esophagus. Proceedings of the National Academy of Sciences USA 2004; 101: 42504255.
82.Echániz-Aviles, G, et al. Molecular characterisation of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone in a Mexican hospital (1999–2003). Clinical Microbiology and Infection 2006; 12: 2228.