Increased risk of incident primary cancer after Staphylococcus aureus bacteremia: A matched cohort study.

Susceptibility to infectious disease may be a marker of immunodeficiency caused by unrecognized cancer. To test the hypothesis, the risk of incident primary cancer was estimated among survivors of Staphylococcus aureus bacteremia (SAB) and compared to a random population cohort.Nation-wide population-based matched cohort study. Cases of SAB were identified from a national database and incident primary cancers were ascertained by record linkage. Incidence rate (IR) and ratio (IRR) with 95% confidence interval (CI) of 27 cancers was calculated by Poisson regression.During the first year of follow-up, 165 and 943 incident cases of cancer occurred in the case cohort (n = 12,918 (1.3%)) and the population cohort (n = 117,465 (0.8%)) for an IR of 3.78 (3.22-4.40) and 2.28 (2.14-2.43) per 100,000 person-years. The IRR was 1.65 (1.40-1.95). Of 27 cancers, 7 cancers occurred more frequently amongst cases than controls: cervical cancer (IRR 37.83 (4.23-338.47)), multiple myeloma (IRR 6.31 (2.58-15.44)), leukemia (IRR 4.73 (2.21-10.10)), sarcoma (IRR 4.73 (1.18-18.91)), liver cancer (IRR 3.64 (1.30-10.21)), pancreatic cancer (IRR 2.8 (1.27-6.16)), and urinary tract cancer (IRR 2.58 (1.23-5.39)). Compared to the control population, the risk of cancer was higher for those without comorbidity and with younger age. The overall risk of cancer during 2 to 5 years of follow-up was not increased (IRR 0.99 (95% CI: 0.89-1.11). However, the risk of pharyngeal cancer was increased (IRR 1.88 (1.04-3.39)) and the risk of liver cancer remained increased (IRR 3.93 (2.36-6.55)).The risk of primary incident cancer was 65% higher in the SAB cohort compared to the population cohort during the first year of follow-up and included 7 specific cancers. The risk was higher for those without comorbidity and with younger age. Screening for these specific cancers in selected populations may allow for earlier detection.

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.

Identification of a PVL-negative SCCmec-IVa sublineage of the methicillin-resistant Staphylococcus aureus CC80 lineage: understanding the clonal origin of CA-MRSA.

OBJECTIVES: Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to clonal complex 80 (CC80) are recognized as the European CA-MRSA. The prevailing European CA-MRSA clone carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses Panton-Valentine leukocidin (PVL). Recently, a significant increase of PVL-negative CC80 MRSA has been observed in Denmark. The aim of this study was to examine their genetics and epidemiology, and to compare them to the European CA-MRSA clone in order to understand the emergence of PVL-negative CC80 MRSA. METHODS: Phylogenetic analysis of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 methicillin-susceptible S. aureus and 194 MRSA) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiologic data were obtained for selected isolates. RESULTS: Phylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: (a) an methicillin-susceptible S. aureus clade encompassing Sub-Saharan African isolates (n = 13); (b) a derived clade encompassing the European CA-MRSA SCCmec-IVc clone (n = 185); and (c) a novel and genetically distinct clade encompassing MRSA SCCmec-IVa isolates (n = 19). All isolates in the novel clade were PVL negative, but carried remnant parts (8-12 kb) of the PVL-encoding prophage ΦSa2 and were susceptible to fusidic acid and kanamycin/amikacin. Geospatial mapping could link these isolates to regions in the Middle East, Asia and South Pacific. CONCLUSIONS: This study reports the emergence of a novel CC80 CA-MRSA sublineage, showing that the CC80 lineage is more diverse than previously assumed.

Report of mecC-carrying MRSA in domestic swine.

OBJECTIVES: We unexpectedly identified MRSA isolates carrying mecC (mecC-MRSA) from a Danish swine farm located in eastern Zealand. The objective of the present study was to investigate the origin of these isolates and their genetic relatedness to other mecC-MRSA isolates from Zealand. METHODS: WGS was used to infer the phylogenetic relationship between 19 identified mecC-MRSA isolates from the swine farm and 34 additional epidemiologically unrelated human isolates from the same geographical region of Denmark. Variations in the accessory genome were investigated by bioinformatics tools, and antibiotic susceptibility profiles were assessed by MIC determination. RESULTS: mecC-MRSA was isolated from a domestic swine farm, but not from cattle reared at the same farm. Phylogenetic analysis revealed that all mecC-MRSA isolates from both farm animals and workers formed a separate cluster, whereas human isolates from the same municipality belonged to a closely related cluster. Analysis of the accessory genome supported this relationship. CONCLUSIONS: To the best of our knowledge, this is the first report of mecC-MRSA isolated from domestic swine. The investigation strongly indicates that transmission of mecC-MRSA has taken place on the swine farm between the farmers and swine. The close clustering of farm isolates and isolates from the same municipality suggests a local transmission of mecC-MRSA.

Long-term mortality and causes of death associated with Staphylococcus aureus bacteremia. A matched cohort study.

OBJECTIVES: Data describing long-term mortality in patients with Staphylococcus aureus bacteremia (SAB) is scarce. This study investigated risk factors, causes of death and temporal trends in long-term mortality associated with SAB. METHODS: Nationwide population-based matched cohort study. Mortality rates and ratios for 25,855 cases and 258,547 controls were analyzed by Poisson regression. Hazard ratio of death was computed by Cox proportional hazards regression analysis. RESULTS: The majority of deaths occurred within the first year of SAB (44.6%) and a further 15% occurred within the following 2-5 years. The mortality rate was 14-fold higher in the first year after SAB and 4.5-fold higher overall for cases compared to controls. Increasing age, comorbidity and hospital contact within 90 days of SAB was associated with an increased risk of death. The overall relative risk of death decreased gradually by 38% from 1992-1995 to 2012-2014. Compared to controls, SAB patients were more likely to die from congenital malformation, musculoskeletal/skin disease, digestive system disease, genitourinary disease, infectious disease, endocrine disease, injury and cancer and less likely to die from respiratory disease, nervous system disease, unknown causes, psychiatric disorders, cardiovascular disease and senility. Over time, rates of death decreased or were stable for all disease categories except for musculoskeletal and skin disease where a trend towards an increase was seen. CONCLUSION: Long-term mortality after SAB was high but decreased over time. SAB cases were more likely to die of eight specific causes of death and less likely to die of five other causes of death compared to controls. Causes of death decreased for most disease categories. Risk factors associated with long-term mortality were similar to those found for short-term mortality. To improve long-term survival after SAB, patients should be screened for comorbidity associated with SAB.

Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia: A matched cohort study.

OBJECTIVES: An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB). METHODS: Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population. RESULTS: Within a year, 278 of 15,669 SAB patients and 2570 of 156,690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE. CONCLUSIONS: SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB.

Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region.

The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergötland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergötland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clone's persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83% (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68% (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergötland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.

Increased risk of venous thromboembolism within the first year after Staphylococcus aureus bacteraemia: a nationwide observational matched cohort study.

OBJECTIVES: Recent evidence suggests that there is an association between infection and venous thromboembolism (VTE). Here, we examined the risk of VTE after Staphylococcus aureus bacteraemia (SAB) compared to the risk in control subjects. DESIGN AND SETTING: Register-based nationwide observational cohort study of hospitalized patients and matched control subjects from the general population in Denmark between 1995 and 2008. RESULTS: Amongst 15 669 SAB cases and 156 690 controls, 182 and 511, respectively, experienced VTE within 1 year. The overall incidence rate (IR) of VTE amongst cases was highest within the first 30 days [IR of deep vein thrombosis (DVT), 39.3 (95% confidence interval (CI) 28.9-53.4)/1000 person-years (PYs); IR of pulmonary embolism (PE), 16.3 (95% CI 10.1-26.2)/1000 PYs]. IRs of DVT were particularly increased amongst cases with a previous diagnosis of VTE, community-acquired infection, a history of injection drug use and in younger age groups. The overall hazard ratio of VTE for cases compared to controls declined from 15.6 (95% CI 10.3-23.5) in the first 30 days after SAB to 4.5 (95% CI 3.2-6.2) from 181 to 365 days after infection. The increased risk of VTE amongst SAB patients persisted after excluding cases with identified VTE risk factors. CONCLUSIONS: There was a particularly high risk of VTE during the first month following an episode of SAB. The risk declined over time, but remained at a threefold increased level compared to control subjects, suggesting that there are shared risk factors for SAB and VTE. Patients with SAB and well-documented risk factors for VTE may benefit from thromboprophylaxis.

A nationwide study of comorbidity and risk of reinfection after Staphylococcus aureus bacteraemia.

BACKGROUND: Data on risk factors and rates of reinfection associated with Staphylococcus aureus bacteraemia (SAB) are sparse. METHODS: We conducted a nationwide cohort study of cases of SAB diagnosed between 1995 and 2008. Reinfection was defined as an episode of SAB more than 90 days after the initial episode of SAB. Comorbidity was evaluated by the Charlson Comorbidity Index (CCI). Cox proportional hazards modelling was used to estimate hazard rates (HR). RESULTS: Of 10,891 eligible patients, 774 (7.1%) experienced reinfection a median of 458 days (range 90-5021 days) after their primary SAB episode corresponding to a reinfection rate of 1459 (95% confidence interval (CI): 1357-1562) per 100,000 personyears. In multivariate analysis, sex, origin, a vascular or peritoneal device, endocarditis and comorbidity were associated with reinfection. The association was more than two-fold higher among patients in dialysis and for patients with severe comorbidity (CCI ≥ 2). HIV infection (Hazard ratio (HR) 6.18, 95% CI: 4.17-9.16), renal disease (HR 3.92, 95% CI: 3.22-4.78), diabetes with complications (HR 2.11, 95% CI: 1.69-2.62), diabetes without complications (HR 1.61, 95% CI: 1.34-1.93), mild (HR: 1.94, 95% CI: 1.36-2.76) and severe liver disease (HR 2.08, 95% CI: 1.08-4.03), peptic ulcer (HR 1.33, 95% CI: 1.03-1.72), and paraplegia (HR 2.15, 95% CI: 1.02-4.54) were each associated with an increased risk of reinfection. CONCLUSIONS: Patients with previous SAB have a 60-fold higher risk of SAB compared to the general population. Patients with HIV infection, renal disease, diabetes, liver disease, peptic ulcer and paraplegia had the highest rates of reinfection.

Epidemiology of methicillin-resistant Staphylococcus aureus carrying the novel mecC gene in Denmark corroborates a zoonotic reservoir with transmission to humans.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated (HA), community-associated (CA) and livestock-associated (LA) infections. Recently, the discovery of human and bovine MRSA isolates carrying a new mecA gene homologue, mecA(LGA251) (now designated mecC), has caused concern because they are not detected by conventional, confirmatory tests for MRSA. Very little is known about their frequency, epidemiology and possible transmission between livestock and humans. In this study, the epidemiology of the mecC isolates in Denmark was investigated by screening the national collections of MRSA cases (from 1988 onwards) and S. aureus bacteraemia cases (from 1958 onwards). Isolates carrying mecC were only recovered infrequently before 2003 (n = 2) but now seem to be increasing, with 110 cases in 2003-2011. Clinical data on mecC-carrying MRSA demonstrated that mecC-MRSA were primarily community-acquired (CA-MRSA) and affected persons typically living in rural areas, being older than other CA-MRSA patients. Among 22 cases in Region Zealand, four reported contact with cattle and sheep. Two of these persons lived on farms with livestock positive for mecC-carrying MRSA, sharing spa type (t843), MLVA (MT429) and PFGE pattern with the human isolates. These observations indicate that mecC-carrying MRSA can be exchanged between humans and ruminants.

First detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012.

Livestock-associated meticillin-resistant Staphylococcus aureus belonging to clonal complex 398 (LA-MRSA CC398) is an important cause of zoonotic infections in several countries, but there is only a single published report of this lineage from the United Kingdom (UK). Here, we describe the isolation of LA-MRSA CC398 from bulk tank milk from five geographically dispersed farms in the UK. Our findings suggest that LA-MRSA CC398 is established in livestock in the UK. Awareness of the potential occupational risks and surveillance in other food-producing animal species should be promoted.

The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species.

OBJECTIVES: A previously unidentified mecA homologue, mecA(LGA251), has recently been described in methicillin-resistant Staphylococcus aureus (MRSA) from humans and dairy cattle. The origin and epidemiology of this novel homologue are unclear. The objective of this study was to provide basic descriptive information of MRSA isolates harbouring mecA(LGA251) from a range of host animal species. METHODS: A number of S. aureus isolates from historical animal isolate collections were chosen for investigation based on their similarity to known mecA(LGA251) MRSA isolates. The presence of mecA(LGA251) was determined using a multiplex PCR and antimicrobial susceptibility testing performed by disc diffusion. RESULTS: MRSA harbouring mecA(LGA251) were found in isolates from a domestic dog, brown rats, a rabbit, a common seal, sheep and a chaffinch. All of the isolates were phenotypically MRSA, although this depended on which test was used; some isolates would be considered susceptible with certain assays. All isolates were susceptible to linezolid, rifampicin, kanamycin, norfloxacin, erythromycin, clindamycin, fusidic acid, tetracycline, trimethoprim/sulfamethoxazole and mupirocin. Five multilocus sequence types were represented (2273, 130, 425, 1764 and 1245) and six spa types (t208, t6293, t742, t6594, t7914 and t843). CONCLUSIONS: The discovery of MRSA isolates possessing mecA(LGA251) from a diverse range of host species, including different taxonomic classes, has important implications for the diagnosis of MRSA in these species and our understanding of the epidemiology of this novel mecA homologue.

Rapid detection, differentiation and typing of methicillin-resistant Staphylococcus aureus harbouring either mecA or the new mecA homologue mecA(LGA251).

The recent finding of a new mecA homologue, mecA(LGA251) , with only 70% nucleotide homology to the conventional mecA gene has brought the routine testing for mecA as a confirmatory test for methicillin-resistant Staphylococcus aureus (MRSA) into question. A multiplex PCR was designed to differentiate mecA(LGA251) from the known mecA together with detection of lukF-PV and the spa gene fragments, enabling direct spa typing by sequencing of the PCR amplicons. The PCR analysis and subsequent spa typing were validated on a large collection (n=185) of contemporary MRSA and methicillin-sensitive S. aureus isolates, including 127 isolates carrying mecA(LGA251) . The mecA(LGA251) gene was situated in staphylococcal cassette chromosome mec type XI elements, and sequence variation within a 631-bp fragment of mecA(LGA251) in 79 isolates indicated a very conserved gene sequence. Following a successful validation, the multiplex PCR strategy was implemented in the routine testing of MRSA for national surveillance. Over a 2-month period, among 203 samples tested, 12 new MRSA cases caused by isolates carrying mecA(LGA251) were identified, emphasizing the clinical importance of testing for these new MRSA isolates.

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.

Comparative genomic analysis of European and Middle Eastern community-associated methicillin-resistant Staphylococcus aureus (CC80:ST80-IV) isolates by high-density microarray.

Infections as a result of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are an issue of increasing global healthcare concern. In Europe, this principally involves strains of multi-locus sequence type clonal complex 80 sequence type 80 with methicillin resistance in a staphylococcal chromosomal cassette (SCCmec) type IV arrangement (CC80:ST80-IV). As with other CA-MRSA strains, CC80:ST80-IV isolates tend to appear uniform when analysed by common molecular typing methods (e.g. pulsed field gel electrophoresis, multi-locus sequence type, SCCmec). To explore whether DNA sequence-based differences exist, we compared the genetic composition of six CC80:ST80-IV isolates of diverse chronological and geographic origin (i.e. Denmark and the Middle East) using an Affymetrix high-density microarray that was previously used to analyse CA-MRSA USA300 isolates. The results revealed a high degree of homology despite the diversity in isolation date and origin, with isolate differences primarily in conserved hypothetical open reading frames and intergenic sequences, but also including regions of known function. This included the confirmed loss of SCCmec recombinase genes in two Danish isolates representing potentially new SCCmec types. Microarray analysis grouped the six isolates into three relatedness pairs, also identified by pulsed field gel electrophoresis, which were consistent with both the clinical and molecular data.

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.

spa typing directly from a mecA, spa and pvl multiplex PCR assay-a cost-effective improvement for methicillin-resistant Staphylococcus aureus surveillance.

Rapid detection and typing of methicillin-resistant Staphylococcus aureus are important components of infection control programmes. A protocol is described that enables sequencing of the spa gene fragment directly from a multiplex PCR targeting the clinically relevant mecA, pvl and spa genes, resulting in high-throughput characterisation of S. aureus. Implementation of the method in the Danish national reference laboratory has markedly reduced the use of reagents and the requirement for hands-on time, and has also provided fast typing results. In addition, the method reduces the risk of sample mishandling.

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.

Epidemiology of European community-associated methicillin-resistant Staphylococcus aureus clonal complex 80 type IV strains isolated in Denmark from 1993 to 2004.

In Europe, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been caused predominantly by isolates belonging to the "European CA-MRSA" clone (sequence type 80, staphylococcal cassette chromosome mec type IV). In this study, the epidemiology of European CA-MRSA was investigated on a nationwide scale, covering the period from 1993 to 2004. Denmark has been a low-prevalence country regarding MRSA since the mid-1970s but has experienced an increase in the number of new MRSA cases in recent years. Our results show that European CA-MRSA contributed to this increase. The isolates primarily caused skin and soft tissue infections (SSTIs) in patients outside hospitals, and transmission between household members was the predominant mode of spread. Although some of the isolates were found in hospitalized patients, nosocomial transmission seemed likely in only one instance, pointing to endogenous infections as an important factor. Compared to the CA-MRSA clone most common in the United States (USA300), the European CA-MRSA clone seems less well adapted to persist in hospital environments. Patients with a recent history of travel or family relation to the Mediterranean or Middle East were highly overrepresented. The epidemiological data indicated that the European CA-MRSA isolates were introduced into Denmark on multiple occasions, paralleled by an increasing level of genetic diversity of the isolates found during the study period. European CA-MRSA has previously been described as a rather uniform clone. However, we found pronounced, diverse pulsed-field gel electrophoresis subtypes, staphylococcal protein A gene (spa) types, and susceptibility patterns.

Characterization of the epidemic European fusidic acid-resistant impetigo clone of Staphylococcus aureus.

Resistance to the antibiotic fusidic acid in European strains of Staphylococcus aureus causing impetigo has increased in recent years. This increase appears to have resulted from clonal expansion of a strain we have designated the epidemic European fusidic acid-resistant impetigo clone (EEFIC), which carries the fusidic acid resistance determinant fusB on its chromosome. To understand better the properties of the EEFIC responsible for its success, we have performed detailed phenotypic and genotypic characterization of this clone. Molecular typing revealed the EEFIC to be ST123, spa type t171, and agr type IV and therefore unrelated to earlier prevalent fusB(+) strains found in the United Kingdom. EEFIC strains exhibited resistance to fusidic acid, penicillin, and, in some cases, erythromycin, which are all used in the treatment of impetigo. PCR analysis of the EEFIC and complete DNA sequencing of the 39.3 Kb plasmid it harbors identified genes encoding several toxins previously implicated in impetigo (exfoliative toxins A and B and EDIN-C). The location of fusB was mapped on the chromosome and found to be associated with a novel 16.6-kb genomic island integrated downstream of groEL. Although this element is related to classical staphylococcal pathogenicity islands, it does not encode any known virulence factors and consequently has been designated SaRI(fusB) (for "S. aureus resistance island carrying fusB").