Implications of identifying the recently defined members of the Staphylococcus aureus complex S. argenteus and S. schweitzeri: a position paper of members of the ESCMID Study Group for Staphylococci and Staphylococcal Diseases (ESGS).

BACKGROUND: Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of 'classical' S. aureus, while as yet no S. schweitzeri infections have been reported. AIM: To provide decision support on whether and how to distinguish and report both species. SOURCES: PubMed, searched for S. argenteus and S. schweitzeri. CONTENT: This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. IMPLICATIONS: We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. 'member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates.

Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin-resistant Staphylococcus aureus: Blurring of the traditional definitions.

The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification.

Systematic literature analysis and review of targeted preventive measures to limit healthcare-associated infections by meticillin-resistant Staphylococcus aureus.

Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections in Europe. Many examples have demonstrated that the spread of MRSA within healthcare settings can be reduced by targeted infection control measures. The aim of this systematic literature analysis and review was to summarise the evidence for the use of bacterial cultures for active surveillance the benefit of rapid screening tests, as well as the use of decolonisation therapies and different types of isolation measures. We included 83 studies published between 2000 and 2012. Although the studies reported good evidence supporting the role of active surveillance followed by decolonisation therapy, the effectiveness of single-room isolation was mostly shown in non-controlled studies, which should inspire further research regarding this issue. Overall, this review highlighted that when planning the implementation of preventive interventions, there is a need to consider the prevalence of MRSA, the incidence of infections, the competing effect of standard control measures (e.g. hand hygiene) and the likelihood of transmission in the respective settings of implementation.

Risk factors for Staphylococcus aureus nasal colonization in Danish middle-aged and elderly twins.

Staphylococcus aureus is a human commensal bacterium found in the nasal cavity and other body sites. Identifying risk factors for S. aureus nasal carriage is of interest, as nasal carriage is a risk factor for subsequent invasive infection. We recently investigated the influence of host genetics on S. aureus carriage in Danish middle-aged and elderly twins, which indicated no significant heritability that could account for the observed S. aureus carriage. In the present study, we performed a questionnaire-based study of S. aureus colonization on the same cohort of 2,196 Danish middle-aged and elderly twins to identify specific risk factors for S. aureus nasal colonization, including analyzing the paired twins (n = 478) that were discordant for S. aureus colonization. We found associations between risk factors and S. aureus nasal colonization among middle-aged and elderly twins, including age, male gender, psoriasis, and atopic diseases. Also, present living on a farm is clearly associated with S. aureus colonization, while smoking had a borderline statistically significant protective effect.

Comparison of Rosco Neo-Sensitabs with Oxoid paper disks in EUCAST disk diffusion antimicrobial susceptibility testing on Mueller-Hinton agar.

This study compared Neo-Sensitabs with Oxoid paper disks using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) disk diffusion antimicrobial susceptibility test on Mueller-Hinton agar. The EUCAST-recommended quality control strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) (Part I) and clinical isolates (Part II) were investigated. In Part I of the study, 27 combinations of antimicrobial agents were tested on four quality control strains repeatedly up to 60 times and zone diameters of tablets and disks were compared. In Part II of the study, 351 clinical isolates were included to cover a broad range of species, as well as resistance mechanisms. In Part I, four major deviations (>1 mm outside quality control ranges) were observed with Neo-Sensitabs. In one case with P. aeruginosa ATCC 27853 (meropenem), there was a corresponding major deviation (2 mm) with the Oxoid disk. The three remaining major deviations with Neo-Sensitabs were observed with meropenem (2 mm) in E. coli ATCC 25922 and with ciprofloxacin (2 mm) and gentamicin (3 mm) in P. aeruginosa ATCC 27853. For Oxoid disks, there were only minor deviations (=1 mm outside quality control ranges) in these three cases. In Part II, there were six discrepancies, susceptible versus resistant, in 3,533 comparisons between the two methods with the clinical isolates. The Rosco Neo-Sensitabs appear to be a possible alternative to Oxoid paper disks for EUCAST disk diffusion antimicrobial susceptibility testing on Mueller-Hinton agar.

Public health impact and antimicrobial selection of meticillin-resistant staphylococci in animals.

Whilst meticillin-resistant Staphylococcus aureus (MRSA) infections reported sporadically in companion animals and cattle in the 1970s were probably of human origin, the recently emerged livestock-associated MRSA (LA-MRSA) and meticillin-resistant Staphylococcus pseudintermedius (MRSP) strains clearly have animal origins and their isolation from humans is usually associated with exposure to livestock and companion animals, respectively. LA-MRSA is primarily an occupational health risk to farm workers and veterinarians. The risk that this zoonotic agent may spread in the community is particularly acute in countries with high livestock production and low MRSA prevalence in the human population. MRSP is primarily a threat to animal health, and cases of human infection are rare but may be overlooked in diagnostic laboratories. There is no conclusive evidence of antimicrobial selection associated with the sudden emergence of LA-MRSA and MRSP. However, the rapid global spread of these bacteria has presumably been favoured by antimicrobial selective pressure. Tetracyclines, zinc and extended-spectrum cephalosporins (including extra-label use) are the most likely selective drivers implicated in the spread of LA-MRSA, whilst increased use of broad-spectrum ß-lactams and fluoroquinolones, partly enhanced by extra-label use and the introduction of cheap generics, may have played an important role in the rapid dissemination of MRSP. Control of LA-MRSA and MRSP requires a dual approach aimed at reducing antimicrobial consumption and preventing transmission between animals and from animals to humans or vice versa. Restricted use of fluoroquinolones and cephalosporins in livestock, and national practice guidelines for rational antimicrobial use both in food and companion animals are warranted.

Farm-specific lineages of methicillin-resistant Staphylococcus aureus clonal complex 398 in Danish pig farms.

The objective of this study was to investigate the genetic diversity of methicillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 using pulsed-field gel electrophoresis (PFGE). Dust and pigs at five age groups were sampled in six Danish MRSA-positive pig farms. MRSA CC398 was isolated from 284 of the 391 samples tested, including 230 (74%) animal and 54 (68%) environmental samples. PFGE analysis of a subset of 48 isolates, including the six strains previously isolated from farm workers, revealed the existence of farm-specific pulsotypes. With a single exception, human, environmental and porcine isolates originating from the same farm clustered together in the PFGE cluster analysis, indicating that spread of MRSA CC398 in Danish pig farms is mainly due to clonal dissemination of farm-specific lineages that can be discriminated by PFGE. This finding has important implications for planning future epidemiological studies investigating the spread of CC398 in pig farming.

Distribution of fusidic acid resistance determinants in methicillin-resistant Staphylococcus aureus.

The prevalence of resistance to fusidic acid in clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), has increased in the past 2 decades. However, there are limited data regarding the relative importance in this process of the different staphylococcal determinants that mediate resistance to fusidic acid. Furthermore, the roles played by clonal dissemination of fusidic acid-resistant strains versus horizontal transmission of fusidic acid resistance determinants have not been investigated in detail. To gain insight into both issues, we examined fusidic acid resistance in 1,639 MRSA isolates collected in Denmark between 2003 and 2005. Resistance to fusidic acid (MIC, >1 µg/ml) was exhibited by 291 (17.6%) isolates. For the majority of these isolates (∼87%), resistance was attributed to carriage of fusB or fusC, while the remainder harbored mutations in the gene (fusA) encoding the drug target (EF-G). The CC80-MRSA-IV clone carrying fusB accounted for ∼61% of the resistant isolates in this collection, while a single CC5 clone harboring fusC represented ∼12% of the resistant strains. These findings emphasize the importance of clonal dissemination of fusidic acid resistance within European MRSA strains. Nonetheless, the distribution of fusB and fusC across several genetic lineages, and their presence on multiple genetic elements, indicates that horizontal transmission of fusidic acid resistance genes has also played an important role in the increasing prevalence of fusidic acid resistance in MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe.

Methicillin-resistant Staphylococcus aureus (MRSA) isa major cause of healthcare- and community-associated infections worldwide. Within the healthcare setting alone, MRSA infections are estimated to affect more than 150,000 patients annually in the European Union (EU), resulting in attributable extra in-hospital costs of EUR 380 million for EU healthcare systems. Pan-European surveillance data on bloodstream infections show marked variability among EU Member States in the proportion of S. aureus that are methicillin-resistant, ranging from less than 1% to more than 50%. In the past five years, the MRSA bacteraemia rates have decreased significantly in 10 EU countries with higher endemic rates of MRSA infections. In addition to healthcare-associated infections, new MRSA strains have recently emerged as community and livestock-associated human pathogens in most EU Member States. The prevention and control of MRSA have therefore been identified as public health priorities in the EU. In this review, we describe the current burden of MRSA infections in healthcare and community settings across Europe and outline the main threats caused by recent changes in the epidemiology of MRSA. Thereby, we aim at identifying unmet needs of surveillance, prevention and control of MRSA in Europe.

The search and destroy strategy prevents spread and long-term carriage of methicillin-resistant Staphylococcus aureus: results from the follow-up screening of a large ST22 (E-MRSA 15) outbreak in Denmark.

In the aftermath of a methicillin-resistant Staphylococcus aureus (MRSA) ST22 hospital outbreak, we investigated the prevalence of long-term carriage, the efficacy of MRSA decolonization treatment (DT) and the spread of MRSA to households of patients and healthcare workers (HCWs). Furthermore, we evaluated the efficacy of repeated DT in long-term MRSA carriers. Of 250 index persons (58 HCWs and 192 patients), 102 persons (19 HCWs and 83 patients) and 67 household members agreed to participate. Samples from all 169 persons were taken from the nose, throat, wounds and devices/catheters, and urine samples were additionally taken from index persons. Samples from companion animals (n = 35) were taken from the nostrils and anus. Environmental sites (n = 490) screened were telephone, television remote control, toilet flush handle, favourite chair and skirting board beside the bed. Sixteen (19%) patients and two household members, but no HCWs, were ST22-positive. The throat was the most frequent site of colonization. In a multivariate analysis, chronic disease (p <0.001) and pharyngeal carriage (p <0.001) were associated with long-term MRSA carriage. MRSA was found in the environments of four long-term carriers. All animals tested were negative. MRSA-positive households were decolonized using nasal mupirocin TID and daily chlorhexidine body and hair wash for 5 days. Pharyngeal MRSA carriers also received fucidic acid (500 mg TID) combined with rifampicin (600 mg BID) or clindamycin (600 mg BID) for 7 days. The home environment was cleaned on days 2 and 5. At the end of follow-up, ten of 16 long-term carriers and the two household contacts were MRSA-negative. In conclusion, decolonization of MRSA carriers is possible, but should include treatment of household members and the environment.

Spa type distribution in Staphylococcus aureus originating from pigs, cattle and poultry.

Methicillin-resistant S. aureus (MRSA) of clonal complex 398 (CC398) is emerging globally among production animals such as cattle, pigs and poultry as well as among humans. However, little is known about the prevalence of CC398 among methicillin sensitive S. aureus (MSSA) or the relative clonal distribution of S. aureus isolated from these three animal reservoirs. To study this, we have analyzed a random sample of S. aureus consisting of 296 epidemiologically unrelated isolates from infections and colonisation of pigs, cattle and poultry. These were examined and compared by spa and multi-locus sequence typing (MLST) and the result was compared to the most common spa types found among human blood isolates. Little overlap in spa types was seen between isolates from the three animal reservoirs or between animals and humans. Most of the porcine isolates had the spa types t034 (CC398), t1333 (CC30) and t337 (CC9), while the bovine isolates mainly had spa types t518 (CC50), t524 (CC97) and t529 (CC151). None of these spa types are common among human blood isolates in Denmark. Surprisingly, almost all of the poultry isolates (96%) belonged to CC5 (spa types t002 and t306), which is also known to be commonly found among human blood isolates and subsequent pulsed-field gel electrophoresis (PFGE) analysis identified indistinguishable PFGE patterns among a poultry isolate and selected human isolates. In conclusion, strains of MSSA CC398 were commonly present in pigs but not present at all in the other reservoirs tested.

Community-associated meticillin-resistant Staphylococcus aureus as a cause of hospital-acquired infections.

The worldwide emergence of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) during the last decade represents a significant change in the biology of MRSA strains and is changing the epidemiology of MRSA infections. CA-MRSA infections are caused by strains belonging to lineages distinct from HA-MRSA. In the community, CA-MRSA strains typically cause skin and soft tissue infections in children and younger adults. However, CA-MRSA strains increasingly cause healthcare-acquired infections including surgical site infections, ventilator-associated pneumonia and bacteraemia. A mathematical model showing the influence of MRSA transmission in the community on the prevalence of MRSA in hospitals is presented. The increasing prevalence of MRSA in the community also results in an increase in community-onset MRSA (CO-MRSA) among S. aureus bacteraemia and other invasive infections. These patients do not have typical risk factors for MRSA. Such changes may have profound implications for the choice of empirical therapy for serious infections where S. aureus is a possible cause. The new and potentially very large reservoir of MRSA in production animals with subsequent transmission to humans represents an additional serious threat to the control of MRSA both in general and as a cause of healthcare-acquired infections. CA-MRSA is thus a matter of serious concern and should be suppressed.

Emergence and characterization of community-associated methicillin-resistant Staphyloccocus aureus infections in Denmark, 1999 to 2006.

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) infections has changed worldwide. From being strictly nosocomial, MRSA is now frequently found as a community-associated (CA) pathogen. Denmark has been a low-prevalence country for MRSA since the mid-1970s but has in recent years experienced an increasing number of CA-MRSA cases. The aim of this study was to describe the emergence of CA-MRSA infections in Denmark. All Danish MRSA specimens and corresponding clinical data from 1999 to 2006 were investigated. Isolates were analyzed by antibiotic resistance and molecular typing and were assigned to clonal complexes (CC). Clinical data were extracted from discharge summaries and general practitioners' notes, from which assessments of community association were made for all infected cases. CA-MRSA cases constituted 29.4% of all MRSA infections (n = 1,790) and an increasing proportion of the annual numbers of MRSA infections during the study period. CA-MRSA was associated with a young age, skin and soft tissue infections, and non-Danish origin. Transmission between household members was frequently reported. Molecular typing showed >60 circulating clones, where 89.4% of the isolates belonged to five CC (CC80, CC8, CC30, CC5, and CC22), 81.2% carried staphylococcal cassette chromosome mec IV, and 163/244 (69.4%) were positive for Panton-Valentine leukocidin. Clinical and microbiological characteristics indicated that import of MRSA occurs frequently. Resistance to > or =3 antibiotic classes was observed for 48.8% of the isolates. The emergence of CA-MRSA in Denmark was caused by diverse strains, both well-known and new CA-MRSA strains. The results suggest multiple introductions of MRSA as an important source for CA-MRSA infections in Denmark.

Methicillin-resistant Staphylococcus aureus: risk factors associated with community-onset infections in Denmark.

The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Denmark has been below 1% for more than 30 years. However, a marked increase in community-onset MRSA (CO-MRSA) started in 2002. To identify possible risk factors for CO-MRSA infections, a nationwide case-control study was conducted in 2004. Cases (34) were patients with CO-MRSA infections; controls (87) were patients with community-onset methicillin-sensitive S. aureus infections (CO-MSSA). Demographic and clinical data and exposures to possible risk factors during the last 24 months were collected with a structured telephone-administered questionnaire. Skin and soft tissue were the predominant sites of infection, both for cases (68%) and for controls (60%). A large proportion of cases (26%) and controls (38%) had an underlying skin disease. The majority of cases (76%) and controls (61%) had received antibiotics within the last 6 months, and 51% and 31%, respectively, had been hospitalized within the previous year. In a multivariate analysis, non-Danish origin, defined as being from or having parents from outside Denmark, was the only independent risk factor for CO-MRSA infection (OR 30.5, 95% CI 3.6-257.3). Prior hospitalization for >7 days within the previous 6 months tended to be associated with CO-MRSA infection (OR 5.7, 95% CI 0.9-36.4). The predominant MRSA clones found in this study were CC80 (26%), CC8 (24%) and CC5 (18%). Resistance to three or more antimicrobial drug classes was seen in 47% of CO-MRSA isolates. Panton-Valentine leukocidin was found in 47% of CO-MRSA isolates. Apart from a non-Danish origin, CO-MRSA shared the same risk factors as CO-MSSA, which makes control a challenge.

Epidemiological differences between the UK and Ireland versus France in Staphylococcus aureus isolates resistant to fusidic acid from community-acquired skin and soft tissue infections.

OBJECTIVES: To characterize the epidemiology of Staphylococcus aureus isolates resistant to fusidic acid isolated from patients with skin and soft tissue infections (SSTIs) in France, the UK and Ireland. METHODS: One hundred and thirty-six S. aureus isolates with an MIC of fusidic acid above 1 mg/L were isolated during the EPISA study from patients more than 2 years old attending their general practitioners for SSTIs. All isolates were related to clonal complex by a combination of PFGE, spa typing and multilocus sequence typing. The presence of toxin genes and of the fusB determinant was monitored to characterize each represented clonal complex. RESULTS: Eight different clonal complexes were identified. CC121 constituted the majority of the isolates from Ireland and the UK but was not represented in France. Among the other clonal complexes, CC8 and CC5 were the most common in the three countries, although the number of French isolates was limited. CC121 was the only clonal complex significantly associated with a skin infection, namely impetigo (P < 0.05). Toxin genes were present in CC121 and CC80. The fusB determinant was also detected in the same clonal complexes. Enterotoxins were found in four clonal complexes (CC1, CC5, CC8 and CC22). CONCLUSIONS: The impetigo clone (CC121: ST123) was present in the majority of S. aureus isolates from the UK and Ireland but was not detected in France. This strain was associated with impetigo, exfoliative toxins and the fusB determinant. No other clonal complex appeared to be dominant in other types of skin infections.

Evaluation of a new 3-h hybridization method for detecting the mecA gene in Staphylococcus aureus and comparison with existing genotypic and phenotypic susceptibility testing methods.

A new 3-h hybridization assay for detection of the staphylococcal mecA gene and the Staphylococcus aureus nuclease gene was evaluated by comparing the assay with existing genotypic and phenotypic methods. A total of 275 S. aureus strains were tested, including 257 epidemiologically unrelated strains (135 mecA-positive and 122 mecA-negative; collection I), and 18 strains with known borderline resistance to methicillin (collection II). Complete agreement was obtained for both collections when comparing the new assay with genotypic methods. We further evaluated a range of phenotypic susceptibility methods recommended in Europe and/or USA using the presence of the mecA gene as the defining standard. For collection I a high degree of agreement was found for both Etests (256 strains) and the oxacillin screen plate test (255 strains); the degree of agreement was lower for agar dilution methicillin (250 strains) and oxacillin 1 microg discs (239 strains). For the borderline strains a high degree of agreement was only obtained by the oxacillin screen plate test (17 of 18 strains). The other tests were less accurate, in the following order: agar dilution methicillin, Etest methicillin, Etest oxacillin and oxacillin discs with disagreement for four, five, nine and 13 strains, respectively. In conclusion, the new hybridization assay is a rapid and exact method for detecting the mecA gene and the S. aureus nuclease gene. This study confirms that phenotypic tests for methicillin resistance in S. aureus strains creates both false-susceptible and false-resistant results, especially for borderline resistant strains.

Systemic and deep-seated infections caused by Arcanobacterium haemolyticum.

Arcanobacterium haemolyticum has been implicated mainly in non-streptococcal pharyngitis and wound infections. Rarely, it has been reported to cause systemic infection, often in combination with other pathogens. Two cases of systemic and deep-seated infections caused by Arcanobacterium haemolyticum are reported, and the literature is reviewed. Sixteen cases of bacteremia and seven cases of non-bacteremic deep-seated have been published previously. Eight of the bacteremic and two of the non-bacteremic cases occurred in younger, apparently healthy immunocompetent patients. Six patients had infections of the central nervous system. The optimal treatment of infections caused by Arcanobacterium haemolyticum is not known. Although in vitro susceptibility tests have demonstrated tolerance of Arcanobacterium haemolyticum to penicillin, penicillins with or without aminoglycosides have been the most widely used antibiotics, in most cases with success.

Primary gastrointestinal non-Hodgkin's lymphoma in adults: a population-based clinical and histopathologic study.

OBJECTIVES: To analyse the clinical course and the histopathology of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) in adult patients and to investigate a possible impact of Helicobacter pylori. DESIGN/SETTING: Retrospective study of all adult patients in Copenhagen county diagnosed during a 6-year period with NHL. SUBJECTS: A total of 55 patients with GI-NHL diagnosed during the period from 1985 to the end of 1990. RESULTS: Twenty-eight patients had primary lymphoma in the stomach, 14 in the small intestine, 11 in the large intestine and two patients had multifocal involvement. The dominant presenting symptoms were abdominal pain, weight loss, diarrhoea, constipation and fatigue. Acute emergency problems such as severe haemorrhage or perforation at initial presentation were unusual. According to the revised European-American lymphoma (REAL) classification, diffuse large B-cell lymphoma was the most frequent histologic subtype comprising 53% of the cases. Helicobacter pylori infection was documented in 15 of 25 evaluable patients (60%) with gastric lymphomas and was not associated with any specific histological subtype. Endoscopic procedures and barium X-rays were the diagnostic approaches with highest sensitivity. In total, 30 patients (58%) achieved complete remission, 10 (19%) achieved partial remission, and 12 (23%) did not respond to treatment. The overall 5 year survival rate was 0.36 without statistically significant difference between the histological subtypes. Likewise the presence of Helicobacter pylori did not affect survival. CONCLUSION: Primary GI-NHL is a heterogeneous disease entity with considerable therapeutic controversies. No specific clinical or histological phenotype was associated with the presence of Helicobacter pylori.

[Outbreak of methicillin resistant Staphylococcus aureus in a central hospital]. / Udbrud af methicillinresistent Staphylococcus aureus på et centralsygehus.

Until 1994, methicillin resistant Staphylococcus aureus (MRSA) were isolated from less than 60 patients annually in Denmark. We describe an outbreak of MRSA involving eight patients within a timespan of six weeks. Bacteriophage-typing and DNA typing using pulsed field gel electrophoresis revealed that three different strains of MRSA were involved in the outbreak. This emphasizes the importance of typing MRSA in order to clear up the spread in an outbreak. Of the eight patients four died, and in one case MRSA was thought to be the major cause of death. The expenses of the extra hygienic measures i.e. isolation of patients, medication and bacteriological surveillance were estimated to approximately DKK 80.000 pr. patient. Patients, who have been admitted to or worked at a hospital outside Scandinavia within the last six months, are potentially colonized with MRSA. Specific guidelines for hospital hygiene are necessary to prevent the spread of such strains.