a 59-year - old woman with an unremarkable medical history was admitted to limoges university hospital ( france ) in december 2003 for acute respiratory failure . she had a 3-day history of flulike syndrome with fever ,
chills , cough , and myalgia and had been prescribed nonsteroidal antiinflammatory therapy . on admission , she had dyspnea , nonproductive cough , and rales in both lungs .
laboratory studies showed leukopenia ( leukocytes = 1.66  10/l ) , mild thrombocytopenia ( 115,000 platelets / mm ) , hypoxemia ( pao2/fio2 = 61 ) , and lactic acidosis ( ph = 7.29 , lactates = 4.45 mmol / l ) . empirical antibacterial chemotherapy combining ceftriaxone , ciprofloxacin , and gentamicin was started on admission , and mechanical ventilation was immediately necessary .
repeated tracheal aspiration was highly productive and showed hemoptysis and sustained intraalveolar plasma leakage . despite fluid resuscitation , continuous catecholamines perfusion , dortrecogin alfa ( activated ) administration ( xigris , eli lilly and company , indianapolis , in , usa ) , and aggressive care ,
her hemodynamic status deteriorated rapidly , leading to multiple organ failure and death < 24 hours after admission .
histopathologic studies showed total destruction of the respiratory epithelium covering the bronchi and bronchioli , together with abundant gram - positive cocci , absence of viable polymorphonuclear cells , and extensive necrosis of the alveolar septa .
s. aureus was isolated 3 times , by culture of blood ( lim-48 ) , lung necropsy tissue ( lim-49 ) , and tracheal aspirate ( lim-50 ) .
the 3 isolates had the same antimicrobial drug resistance profile ( resistant to oxacillin , kanamycin , tobramycin , and gentamicin ) and the same pattern by pulsed - field gel electrophoresis after dna digestion by smai ( data not shown ) .
influenza a virus was detected by polymerase chain reaction and immunofluorescence on the tracheal aspirate , but culture on cell lines was negative .
the influenza a virus has been shown to be capable of destroying the respiratory epithelium from the trachea to the bronchioli ( 1 ) , allowing the pvl - positive ca - mrsa to adhere to the basement membrane ( 4 ) .
pvl may diffuse locally , attracting polymorphonuclear leukocytes by its chemotactic activity and lysing them by its leukotoxicity . because the clinical manifestations corresponded to those of necrotizing pneumonia ,
isolate lim-49 was referred ( lung necropsy culture ) to the french national centre for staphylococci .
the isolate was screened for staphylococcal toxin genes , agr alleles , and the meca gene as described elsewhere ( table ) ( 3,5,6 ) .
the strain had an agr type 1 allele and the luks - pv / lukf - pv genes encoding pvl ( figure ) , but harbored no toxin genes ( sea through see , tsst , eta , and etb genes encoding staphylococcal enterotoxins a though e , toxic shock syndrome toxin , and exfoliative toxins a and b , respectively ) .
the meca gene was detected , together with sccmec type v as described by ito et al .
the single nucleotide difference between st152 and st377 , which is not distinguished by using the usual primers determined by enright et al .
( 8) , was established as st377 by using in - house primers ( forward 5-gga cga agg tca tga tgt att ttt-3  ( nt 327350 ) , reverse 5-ctt cta cgc gct ctc ttt tta ag-3  ( nt 564586 ) , according to the genbank id11211186 of the gmk gene ) to amplify appropriate fragment . to our knowledge
, this is the first description of such a necrotizing pneumonia  associated ca - mrsa clone .
three other st377 strains were referred to the national reference centre for staphylococci in 2003 .
two were isolated from patients in europe ( netherlands and switzerland ) , and 1 from an australia patient ( strain provided by g. nimmo ) .
the patient from the netherlands had been treated for an abscess from which pvl - mrsa was cultured , and the swiss patient had furunculosis .
the 3 isolates harbored the sccmec type v cassette , an agr1 allele , the same toxin gene profile , and macrorestriction pattern , spa type , as our isolate ( figure ) .
pulsed - field gel electrophoresis ( pfge ) pattern and phylogenetic tree of 4 strains st377 .
smai macrorestriction patterns were digitized and analyzed by using gelcompar ii ( applied maths , kortrijk , belgium ) to calculate dice coefficients of correlation and to generate a dendrogram by the unweighted pair group method using arithmetic averages clustering .
we report the identification of a new , emerging , highly virulent pvl - positive ca - mrsa clone that harbors the sccmec type v cassette .
the new clone seems to have spread rapidly in europe , because it has been detected in patients in the netherlands , switzerland , and now in france .
since necrotizing pneumonia is rapidly fatal , as in the patient described here , cases of pvl - positive ca - mrsa infection must be recognized rapidly , especially in case of methicillin resistance .
the therapeutic value of intravenous immunoglobulin containing anti - pvl antibodies has been reported by gauduchon et al .
 necrotizing pneumonia caused by staphylococcus aureus strains carrying the panton - valentin leukocidin gene is a newly described disease entity . 
 we report a new fatal case of necrotizing pneumonia . 
 an s. aureus strain with an agr1 allele and of a new sequence type 377 was recovered , representing a new , emerging , community - acquired methicillin - resistant clone . 
Case Report
Conclusions