MRSA infections among patients in the emergency department: a European multicentre study

Background

MRSA is a therapeutic concern worldwide, and a major agent of community-acquired skin and soft tissue infections (CA-SSTIs). While the US epidemiology of MRSA in CA-SSTIs is well described and reports the high prevalence of the USA300 clone, data on the European situation are lacking.

Objectives

To determine the prevalence and clonal characteristics of MRSA in CA-SSTIs in seven European emergency departments.

Patients and methods

From April to June 2015, patients presenting to the tertiary hospital emergency department with a Staphylococcus aureus CA-SSTI were prospectively enrolled. S. aureus isolates were characterized by antimicrobial susceptibility testing, detection of Panton–Valentine leucocidin encoding genes and spa-typing, MLST and/or DNA microarray.

Results

Two-hundred and five cases of S. aureus-associated CA-SSTIs were included, comprising folliculitis, furuncles, abscesses, paronychia, impetigo, carbuncles and cellulitis. Of the 205 cases, we report an MRSA prevalence rate of 15.1%, with a north (0%) to south (29%) increasing gradient. Fifty-one isolates were Panton–Valentine leucocidin-positive (24.9%), whether MSSA or MRSA, with a heterogeneous distribution between countries. Clonal distribution of MSSA and MRSA showed high diversity, with no predominant circulating clone and no archetypical USA300 CA-MRSA clone.

Conclusions

This original prospective multicentre study highlights stark differences in European MRSA epidemiology compared with the USA, and that the USA300 CA-MRSA clone is not predominant among community-infected patients in Europe.

Introduction

Staphylococcus aureus infections remain a challenge in terms of therapeutic strategies and public health cost worldwide. MRSA strains were first described in the 1960s from nosocomial infections.¹ However, from the beginning of the 2000s, MRSA have been reported as a source of community-acquired infections (CA-MRSA),² primarily in skin and soft tissue infections (SSTIs).³S. aureus SSTIs encompass diverse clinical presentations such as folliculitis, furuncles, abscesses, paronychia, impetigo, carbuncles, cellulitis and necrotizing cellulitis.⁴ These emerging CA-MRSA strains have a distinct genetic background from the traditional healthcare-associated MRSA strains, and specific lineages have emerged on different continents, including the successful USA300 clone [ST8-MRSA-IVa Panton–Valentine leucocidin (PVL)-positive] in the USA and the ST80 clone (ST80-MRSA-IV PVL-positive) in Europe.^5–7 Regarding S. aureus CA-SSTIs, Moran et al.⁵ reported a prevalence of MRSA reaching 78% in the USA in 2004. In Europe, published data report MRSA rates ranging from 0.9% in the Netherlands⁸ to 14.5% in France⁹ and 30.7% in Greece;¹⁰ however, this was with heterogeneous methodologies between countries and compared with the Moran et al.⁵ study. Thus, having a global picture of MRSA prevalence and clonal profile in S. aureus CA-SSTIs in Europe is highly relevant, not least because the assumed emergence of the USA300 clone in Europe may represent a threat.⁶ To address these issues, we conducted a multicentre study inspired by the Moran et al.⁵ study.

Patients and methods

Ethics

Written consent or non-opposition (according to each country-specific regulation) was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki. Approvals from local ethics committees were obtained for all centres. The study was registered on ClinicalTrials.gov as Identifier NCT02796742.

Patients

From 1 April to 30 June 2015, patients (adults and children) presenting to the tertiary hospital emergency department in Badalona (Spain), Brighton (UK), Bucharest (Romania), Lyon (France), Monza (Italy), Patras (Greece) and Tuebingen (Germany) with a S. aureus CA-SSTI were prospectively enrolled, based on the study criteria described by Moran et al.⁵

Methods

After cultures were obtained, S. aureus isolates were characterized by antimicrobial susceptibility testing, detection of PVL encoding genes and spa-typing and/or MLST and/or DNA microarray according to the participating centres' facilities. Demographic, clinical information and bacteriological data were collated using a standardized form.

Results

Over the study period, 205 patients with S. aureus SSTIs were enrolled, ranging from 12 to 44 patients per participating centre. The median age was 35 years (range, 4 months to 96 years old), including 56 children (<18 years old); men accounted for 54.6% of cases. Infections were classified as furuncles and folliculitis (n = 67, 32.7%), abscesses (n = 54, 26.3%), cellulitis (n = 21, 10.2%), necrotizing cellulitis (n = 2, 1.0%), paronychia (n = 15, 7.3%), infected wounds (n = 20, 9.8%), impetigo (n = 18, 8.8%), superficial suppurations (n = 5, 2.4%) (data were not available for three patients). Of the 205 S. aureus isolates, 34 (16.6%) were MRSA. The prevalence of MRSA ranged from 0% in the UK to 29% in Italy (mean rate 15.1%) (Table 1). Italy, Greece and Romania reported MRSA rates >20% (29%, 27.3% and 21.7%, respectively), while France, Germany and the UK had an MRSA rate <10% (7%, 8.3% and 0%, respectively). A wide diversity of genotypes was observed in each country, regardless of methicillin resistance. MSSA isolates comprised 22 different clonal complexes with CC15, CC30 and CC1 being predominant in all countries (13.5%, 11.5% and 10.9%, respectively). Interestingly, seven of the nine isolates belonging to CC398 originated from French patients, another from the UK and the remaining strain was isolated in Italy and was found to be MRSA. Four MSSA of the nine CC398 isolates, all originating from France, belonged to the t571 spa-type, which had been primarily described as associated with severe infections in pigs and farmers in France.¹¹ Regarding MRSA lineage distribution, eight different clonal complexes were described, including CC80 (n = 10), CC1 (n = 7), CC5 (n = 6) and CC22 (n = 4). Although most countries reported MRSA isolates belonging to various clonal complexes, 8 of 12 MRSA (66.7%) isolated in Greece belonged to the European ST80 clone, and in Romania all five MRSA strains belonged to the CC1 clone. Strikingly, USA300 was not detected in this study; just one isolate (from Spain) was assigned to the arginine catabolic mobile element-negative Latin variant (USA300-LV) of this clone.¹² Fifty-one isolates were PVL-positive (24.9%), with a heterogeneous distribution between countries (from 4.3% in Romania to 34.9% in France). Overall, PVL-positive strains were distributed among MSSA and MRSA, except in Greece where PVL was significantly associated with MRSA (P < 0.0001), due to the predominant circulating clone ST80. MRSA antimicrobial susceptibility profiles showed that 20 isolates (58.8%) were resistant to kanamycin and 6 (17.6%) to kanamycin, tobramycin and gentamicin. Moreover, 15 MRSA were resistant to clindamycin (44.1%), 13 to fluoroquinolones (38.2%), 12 to fusidic acid (35.3%) and 3 to co-trimoxazole (8.8%).

Table 1.

Characteristics of S. aureus isolates

		Isolate characteristic, n (%)
City, country	Number	MRSA	PVL+	MRSA-PVL+	MRSA clones (n)
Brighton, UK	20	0 (0)	2 (10)	0 (0)	—
Lyon, France	43	3 (7)	15 (35)	3 (7)	CC80-MRSA-IV [PVL+] (2) CC121-MRSA (1)
Tuebingen, Germany	12	1 (8.3)	3 (25)	1 (8.3)	CC22-MRSA [PVL+] (1)
Badalona, Spain	32	4 (12.5)	9 (28)	3 (9.4)	CC1-MRSA [PVL+] (1) CC5-MRSA (1) CC8-MRSA [PVL+] USA300-LV (1) CC88-MRSA [PVL+] (1)
Bucharest, Romania	23	5 (21.7)	1 (4)	0 (0)	CC1-MRSA (5)
Patras, Greece	44	12 (27.3)	14 (32)	11 (25)	CC80-MRSA-IV [PVL+](8) CC5-MRSA (1) CC5-MRSA [PVL+] (3)
Monza, Italy	31	9 (29)	7 (23)	1 (3.2)	CC22-MRSA (3) CC1-MRSA (1) CC5-MRSA [PVL+] (1) CC398-MRSA (1) CC8-MRSA (1) others (2)
Total	205	34 (16.6)	51 (24.9)	19 (9.3)

Discussion

Inspired by the Moran et al.⁵ study, which efficiently captured the CA-MRSA epidemiology in the USA 10 years ago, we aimed to determine the prevalence of MRSA in S. aureus CA-SSTIs in Europe and to assess whether the highly successful CA-MRSA USA300 clone is prevalent in such infections. We report here that MRSA accounts for 15.1% of cases, which is markedly lower than in the USA (78%).⁵ Notably, we observed a wide inter-country variation ranging from 0% to 29%, with a north-to-south increasing gradient. The limitations of our study are that included centres were not exhaustive of all European countries, as for the Scandinavian countries, and that each country was represented by only one centre, although all participating centres were university hospitals serving a large population. Nevertheless, these findings are in accordance with previous studies on S. aureus infections, strengthening the validity of our methodology.^8–10 The circulating clones, whatever their methicillin resistance or PVL status, appeared to be genetically diverse and with no predominant lineage, except for the ST80 clone in Greece, as already described.⁷ Interestingly, 4.4% (9 of 205) of strains (isolated in France, UK and Italy) belonged to the S. aureus CC398 emerging lineage. Most importantly, the CA-MRSA USA300 clone was not detected in our cohort, suggesting that the success of this CA clone in the USA is not superimposable in Europe, despite some published data reporting its emergence in the continent,¹³ and confirming the predicted global decline of this clone.¹⁴ There are currently no convincing explanations for the lack of epidemiological success of the CA-MRSA USA300 lineage in Europe. However, one could speculate on the effects of cultural and social differences, living conditions, dietary habits and professional mobility.

To the best of our knowledge, this is the first multicentre study investigating the prevalence and characteristics of MRSA in S. aureus CA-SSTIs in Europe. Our study reveals the specificity of the European CA-MRSA epidemiology compared with the US, and tempers the potential threat of USA300 clone in such infections in the European continent. However, given the current major migratory flow from the Middle East and Africa, the European epidemiology of S. aureus infections may be modified noticeably in the near future.

As a conclusion, we can only strongly advocate the characterization of S. aureus isolates by molecular typing in case of severe or recurrent SSTIs, cluster of cases and outbreaks, to monitor any emerging phenomenon and to decolonize patients with such PVL-positive MSSA and MRSA infections.

Funding

This study was conducted as part of our routine work.

Transparency declarations

None to declare.

Acknowledgements

We acknowledge Helene Meugnier and Taissia-Lelekov Boissard for technical support.

Part of this work was presented as on oral communication at the European Congress of Clinical Microbiology and Infectious Diseases in Amsterdam in April 2016 (Abstract number 826).

The following investigators participated in the study: Olivier Monneuse, Hospices Civils de Lyon, France; Toni de Francisco, Badalona, Spain; Pietro Casella, Serena Erbizzoni, Sara Melzi and Davide Oggioni, Vimercate, Italy; Roberta Sala, Desio, Italy; Enrico Calaresu, Monza, Italy; Petinaki Efthimia, School of Medicine, University of Thessaly, Larissa, Greece; Marangos Markos, School of Medicine, University of Patras, Greece; Efthimia Petinaki University of Thessaly, Larissa, Greece; Wiebke Schroeder, University Hospital of Tuebingen, Germany.