Three-year survey of community-acquired methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a French university hospital

doi:10.1016/j.jhin.2005.01.027

Journal of Hospital Infection

Volume 61, Issue 4, December 2005, Pages 321-329

https://doi.org/10.1016/j.jhin.2005.01.027 Get rights and content

Summary

A retrospective survey was conducted at Bicêtre Hospital, France from January 2001 to September 2003 to screen for S. aureus isolates with a typical phenotype previously involved in necrotizing pneumonia in France. They were resistant to oxacillin and kanamycin, of intermediate susceptibility to fusidic acid, and susceptible to tobramycin and fluoroquinolones. Seventeen isolates were found and 16 were viable. The Panton-Valentine leukocidin (PVL) genes, various toxin genes and SCCmec IV and agr3 alleles were detected in all isolates. The clonal origin of these isolates was demonstrated by pulsed-field gel electrophoresis. Fourteen isolates were community-acquired methicillin-resistant Staphylococcus (CA-MRSA) isolated from previously healthy patients with skin or soft tissue infections. Three infections were of nosocomial origin, underlining that these PVL-producing CA-MRSA strains may also be hospital acquired. Five CA-MRSA isolates with an identical resistance phenotype collected in a neighbouring teaching hospital (Hôpital Pitié-Salpétrière, Paris, France) were also PVL positive. Three isolates were clonally related to those of the Bicêtre Hospital whereas two were not. This retrospective study identified PVL-producing CA-MRSA in two Parisian hospitals. The incidence at Bicêtre Hospital was 0.8% of all S. aureus and 2% of all MRSA isolated. Our data indicate that these MRSA isolates might become hospital acquired.

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) remain a major cause of nosocomial infection worldwide.1, 2 The emergence of community-acquired (CA) MRSA that are unrelated to hospital-acquired (HA) MRSA3, 4, 5 has raised considerable concern since this type of S. aureus may be difficult to treat in outpatients. They have been documented in Australia, New Zealand, Europe, the USA and Canada in patients with no risk factors for nosocomial acquisition of MRSA.6, 7, 8, 9, 10, 11, 12, 13 A low prevalence (1%) of MRSA in CA S. aureus infections was reported in children in New York City¹⁴ and in an adult population in Chicago.¹⁵ However, at the University Hospital of Illinois (Chicago), CA-MRSA accounted for up to 22% of all MRSA isolates in children.¹⁶ O'Brien et al.¹⁷ observed the incidence of CA-MRSA to be as high as 42% in certain rural communities in Western Australia. These CA-MRSA strains may be responsible for hospital outbreaks after admission of infected patients and carriers. Hospital transmission among postpartum women has also been documented at the New York Presbyterian Medical Center.¹⁸

Most CA-MRSA strains cause skin and soft tissue infections, such as abscesses and cellulitis,8, 13, 19 but deaths have occurred, mostly among children with necrotizing pneumonia.²⁰ Most S. aureus strains responsible for primary skin infections and necrotizing pneumonia harbour the Panton-Valentine leukocidin (PVL) determinant.13, 21 The PVL locus is carried by a bacteriophage that is present in only a small percentage of S. aureus strains in France.⁷ A recent study established the link between PVL and mecA genes, and that PVL-producing CA-MRSA infections in France are mainly due to a single clone.7, 13 In addition, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing analysis indicated distinct genetic backgrounds associated with specific geographic locations worldwide. This suggests that PVL-producing CA-MRSA have arisen from diverse genetic backgrounds rather than spread as a single clone.¹³ CA-MRSA are also more susceptible than nosocomial MRSA isolates to non-β-lactam antibiotics.7, 13, 22 They harbour the mecA gene on a unique staphylococcal chromosomal cassette (SCC), mec type IV, and belong to the agr group 3.13, 23, 24 Finally, the French CA-MRSA isolates harboured, in addition to the PVL locus, the related lukE–lukD genes coding for another leukocidin frequently recovered from patients with all types of staphylococcal infections.¹³

The first CA-MRSA isolate in France was reported by L'Hériteau et al.¹⁰ in 1999, and the same year, the French Reference Centre for Staphylococcal Toxemia (Lyon, France) reported the first PVL-producing CA-MRSA isolate.⁷ Since then, 64 additional cases have been reported, scattered throughout the country.¹³ These isolates produced the PVL toxin and were resistant to kanamycin, had decreased susceptibility to fusidic acid, and were susceptible to tobramycin and fluoroquinolones. The French Agency for Public Health Surveillance has recently conducted a study in Western France that identified 23 related cases of PVL-producing CA-MRSA from 1999 to 2002.⁶ However, little is known about the prevalence of PVL-producing CA-MRSA in French hospitals. The purpose of our study was to screen for CA-MRSA retrospectively in our hospital, using the antibiotic resistance profile, to study the clinical features of these infections, to evaluate the relatedness of the isolates by PFGE, and to identify associated genetic traits such as toxin gene and accessory gene regulator (agr) profiles.

Section snippets

Study setting

Bicêtre Hospital is a 1000-bed tertiary care teaching facility with 800 adult beds and 200 paediatric beds. The hospital catchment area (south–east suburb of Paris) comprises about 400 000 people.

Screening procedures

S. aureus isolates in the strain collection database of the Microbiology Department of Bicêtre Hospital were reviewed retrospectively during a 33-month period (from January 2001 to September 2003). Only S. aureus isolates resistant to oxacillin and kanamycin, of intermediate susceptibility to fusidic

Case finding

During the study period (from January 2001 to September 2003), 17 S. aureus isolates from different patients were identified with resistance to oxacillin and kanamycin, decreased susceptibility to fusidic acid (minimum inhibitory concentration >2 μg/mL, inhibition diameter <20 mm), and susceptibility to tobramycin and ciprofloxacin (Table I). Eight were isolated in 2001 (0.8% of all the S. aureus isolated in our hospital, and 2.6% of all the MRSA isolated in our hospital), five in 2002 (0.5% of

Discussion

The emergence of PVL-producing MRSA in the community is a major public health threat because these strains are resistant to several antibiotics, such as oxacillin and fusidic acid, used empirically to treat cutaneous infections. However, in contrast to HA-MRSA, these strains were susceptible to fluoroquinolones.1, 2, 13 Unlike previous studies where CA-MRSA were selected from severe infections, here we identified, retrospectively, PVL-producing MRSA isolates based on a specific resistance

Acknowledgements

This work is part of a multi-centre study organized by the Observatoire National de l'Epidemiologie de la Résistance Bactérienne aux Antibiotiques (ONERBA; www.onerba.org) and was supported by the Assistance Publique-Hôpitaux de Paris and by the University Paris XI, South-Paris Medical School (grant UPRES-EA 3539). We are grateful to Dr G. Lina for helpful discussions and for the S. aureus French CA-MRSA reference strain HT20020213.

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Molecular characterisation of Panton-Valentine leucocidin-producing methicillin-resistant Staphylococcus aureus clones isolated from the main hospitals in Taif, KSA
2016, Indian Journal of Medical Microbiology
Introduction: Panton–Valentine leucocidin (PVL) is a bicomponent pore-forming cytolytic toxin encoded by the lukF-PV and lukS-PV genes. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) may carry the pvl genes which may be related to increased disease severity. This study aimed to characterise the PVL-producing MRSA recovered from different Taif Hospitals, Saudi Arabia. Methods: The study included 45 hospital-acquired-MRSA (HA-MRSA) and 26 CA-MRSA strains which were identified from 445 S. aureus strains isolated from different clinical samples. MRSA strains were identified by standard oxacillin salt agar screening procedure and by the detection of the mecA gene by the polymerase chain reaction (PCR). Detection of the S. aureus-specific femA, mecA and pvl genes was performed by multiplex PCR. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was done for coagulase (coa) gene. Results: The staphylococcal cassette chromosome mec types of the 45 HA-MRSA strains were Type I (n = 24), Type II (n = 7) and Type III (n = 14) whereas the 26 CA-MRSA strains were Type IV (n = 14), Type V (n = 11) and one isolate was non-typeable. All the HA-MRSA and six CA-MRSA strains were PVL-negative PCR-RFLP analysis of coa gene showed that PVL-positive MRSA (n = 20) isolates showed six different patterns, and five patterns were shared by PVL-positive methicillin-susceptible S. aureus (MSSA). The eighth pattern was the most frequent in both MRSA and MSSA. Conclusion: PVL is more frequent among CA-MRSA than MSSA. All the HA-MRSA and 25% of CA-MRSA strains were negative for PVL. The pvl gene was related to the severity of infection but not related to coa gene RFLP pattern.
Risk factors and molecular analysis of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus colonization and infection in children
2012, Journal of Microbiology, Immunology and Infection
Limited information is available regarding the role Panton-Valentine leukocidin (PVL) plays in methicillin-susceptible Staphylococcus aureus (MSSA). In this study, we compared the frequency of the PVL gene between MSSA strains isolated from patients with MSSA infections and MSSA strains isolated from patients with evidence of MSSA nasal colonization. We also explored the role that the PVL toxin plays in the ability of MSSA to cause disease as well as the phylogenetic relationship between these S aureus strains.
The presence of MSSA strains was screened among children aged <18 years during routine health maintenance visits and among children aged <7 years at daycare centers or kindergartens during the 2003 to 2008 period. At the same time, clinical MSSA isolates were recovered from patients with various types of bacterial infections. Polymerase chain reaction was applied to detect the presence of the PVL and SEB genes in these strains. The strains were also subjected to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) studies. Clinical features were compared between patients with PVL-positive and those with PVL-negative isolates.
A total of 495 colonizing MSSA and 71 clinical MSSA isolates were used. The prevalence of PVL-positive S aureus was significantly higher among clinical isolates than among colonizing isolates (14/71, 19.7%; 5/495, 1.0%; p < 0.05). In addition, we found that patients with PVL-positive MSSA infections had a significantly longer duration of fever and tended to have higher C-reactive protein levels than patients with PVL-negative MSSA infections. MLST typing of the 19 PVL-positive MSSA isolates revealed ST59, a strain that is similar to the MLST type of community-associated methicillin-resistant Staphylococcus aureus found in Taiwan. The PFGE typing of PVL-positive/ST59 MSSA isolates revealed multiple pulsotypes.
The prevalence of the PVL gene was significantly higher among clinical strains of MSSA (19.7%) than among colonizing strains (1.0%). In addition, patients infected with PVL-positive MSSA strains had fever for a significantly longer duration and tended to have higher C-reactive protein levels than patients with PVL-negative MSSA infections. Our findings imply that PVL may play an important role in the pathogenesis of S aureus infection.
Clinical isolates of Panton-Valentine leucocidin- and γ-haemolysin-producing Staphylococcus aureus: Prevalence and association with clinical infections
2010, Journal of Hospital Infection
Citation Excerpt :
They have been implicated in reports of skin and soft tissue infections and severe and life-threatening infections such as necrotising pneumonia in children and young adults.13,14 Hospital-acquired MRSA producing PVL has also been reported.15 The purpose of this study was to determine the frequency of pvl and hlg genes among S. aureus strains isolated in our institution and to assess their association with clinical infections and with meticillin resistance.
Panton–Valentine leucocidin (PVL) and γ-haemolysin (Hlg) are members of the synergohymenotropic toxin family produced by Staphylococcus aureus and encoded by pvl and hlg genes, respectively. Many reports describe an association between PVL toxin and necrotic lesions involving skin and mucosa. The aim of this study was to determine the prevalence of S. aureus strains carrying pvl and hlg genes and to investigate a possible relationship between pvl- and hlg-positive S. aureus with specific clinical presentations. Between January 2005 and July 2007, a total of 143 S. aureus strains including 58 meticillin-resistant S. aureus (MRSA) and 85 meticillin-susceptible S. aureus were screened for pvl and hlg genes by multiplex polymerase chain reaction. These strains were isolated from 141 patients for whom demographic and clinical data were recorded. Thirty-one (21.7%) and 77 (53.7%) isolates were positive for pvl and hlg genes, respectively. Twenty-one (67.7%) pvl-positive strains were MRSA (P = 0.001). Among pvl-positive strains, 16 (51.6%) were community-acquired. There was a strong association between pvl genes and skin and soft tissue infections, especially abscesses (60% of strains; P = 0.008) and furunculosis (55.5% of strains; P = 0.036). Our findings confirmed the association between pvl-positive strains, cutaneous infections and meticillin resistance in S. aureus.
Staphylococcus aureus pneumonia: When should we evoke it and how to treat it?
2010, Reanimation
Staphylococcus aureus représente une cause rare de pneumonie communautaire. La prévalence des souches de staphylocoques productrices de la leucocidine de Panton et Valentine (LPV) est en constante augmentation dans le monde. Cette toxine est impliquée dans la survenue d’une entité clinique appelée pneumonie nécrosante staphylococcique, au pronostic particulièrement sombre, touchant des sujets sains et immunocompétents. Souvent précédée d’une infection virale rhino-pharyngée, cette pneumonie est caractérisée par l’association d’une fièvre élevée, d’hémoptysies, d’infiltrats alvéolaires multilobaires et d’une leucopénie. L’évolution, souvent mortelle, se fait le plus souvent vers un choc ou une hypoxémie réfractaire. Même si l’incidence des Staphylococcus aureus résistants à la méticilline (SARM) communautaires LPV+ reste faible en France, en cas de forte suspicion, l’antibiothérapie empirique doit couvrir le SARM. Le choix thérapeutique doit prendre en compte les caractéristiques pharmacocinétiques des molécules, et favoriser celles ayant une bonne diffusion pulmonaire. De même, certaines données fondamentales suggèrent l’intérêt des molécules ayant la capacité à bloquer la synthèse de la LPV. Enfin, l’administration précoce d’immunoglobulines intraveineuses pourrait être proposée comme traitement adjuvant.
Staphylococcus aureus is a rare cause of community-acquired pneumonia. However, methicillin resistant S. aureus (MRSA), usually known as a nosocomial pathogen, has emerged as a cause of community-acquired necrotising pneumonia in young healthy patients without classic health-care-associated risk factors. Community-onset necrotising pneumonia due to CA-MRSA is now recognised as an emerging clinical entity (it still rarely described in France) with distinctive clinical features and substantial morbidity and mortality. A viral prodrome (e.g., influenza or influenza-like illness) followed by acute onset of shortness of breath, sepsis, and haemoptysis is the most frequent clinical presentation. Clinicians had to be aware of this cause of community-acquired pneumonia. Indeed in such patients treatment of community-acquired pneumonia should include an appropriate antibiotic treatment to cover MRSA and to decrease toxin production. In some cases, the adjunctive use of intravenous immunoglobulin may be indicated.
Virulence properties of methicillin-susceptible Staphylococcus aureus food isolates encoding Panton-Valentine Leukocidin gene
2010, International Journal of Food Microbiology
In this study, three Panton–Valentine Leukocidin gene carrying methicillin-susceptible Staphylococcus aureus (MSSA) strains (M1-AAG42B, PY30C-b and YF1B-b) were isolated from different food samples in Kesan—Edirne, Turkey. These strains were characterized on the basis of MLST type, spa type, virulence factor gene contents, antibiotic susceptibilities against 21 antibiotics and biofilm formation. The genetic relatedness of the strains was determined by PFGE. In addition, the complete gene sequences of lukS-PV and lukF-PV were also investigated. All strains were found to be susceptible to tested antibiotics and they were mecA negative. Three strains showed the same PFGE band pattern, ST152 clonal type and t355 spa type. In the detection of virulence factor genes, sea, seb, sec, sed, see, seg, seh, sei, sej, sek, sel, sem, sen, seo, sep, seq, seu, eta, etb, set1, geh and tst genes were not detected. All strains showed the positive results for α- and β-haemolysin genes (hla and hlb), protease encoding genes (sspA, sspB and aur), lukE and lukD leukocidin genes (lukED). The strains were found to be non-biofilm formers. By this study, the virulence properties of the strains were described and this is one of the first reports regarding PVL-positive MSSA strains from food.
Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe
2010, The Lancet Infectious Diseases
Over the past decade, community-associated meticillin-resistant Staphylococcus aureus (MRSA) has emerged in patients without health-care contact, especially in the USA. Although data are limited, the prevalence of community-associated MRSA in Europe seems to be low but is increasing. The organism has been reported in most European countries, including the Netherlands and Nordic countries, which have low rates of health-care-associated MRSA. In Greece, rates of community-associated MRSA in some centres approach those of the USA. By contrast with North America, where the USA300 clone (ST8-IV) predominates, community-associated MRSA in Europe is characterised by clonal heterogeneity. The most common European strain is the European clone (ST80-IV), although reports of USA300 are increasing. Several community-associated MRSA clones have arisen in Europe, most notably the ST398-V pig-associated MRSA clone in the Netherlands and Denmark. An understanding of the epidemiology of community-associated MRSA is essential to guide new control initiatives to prevent these organisms from becoming endemic in Europe.

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Three-year survey of community-acquired methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a French university hospital

Summary

Introduction

Section snippets

Study setting

Screening procedures

Case finding

Discussion

Acknowledgements

Int J Antimicrob Agents

Pathology

Pathology

Lancet

The worldwide problem of methicillin-resistant Staphylococcus aureus

Drugs Exp Clin Res

Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community

J Clin Microbiol

Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors

Clin Infect Dis

Bull Epidemiol Hebdo

Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin

Clin Infect Dis

Community-acquired methicillin resistant Staphylococcus aureus in hospitalized adults and children without known risk factors

Clin Infect Dis

Community-acquired methicillin-resistant Staphylococcus aureus and familial transmission

JAMA

Community-acquired methicillin-resistant Staphylococcus aureus isolated in Switzerland contains the Panton-Valentine leukocidin or exfoliative toxin genes

J Clin Microbiol

Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996–1998

Clin Infect Dis

Community-acquired methicillin-resistant Staphylococus aureus carrying the Panton-Valentine leukocidin genes: worldwide emergence

Emerg Infect Dis