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. Her arterial pressure was 60/30 mm Hg. Skin rash and diarrhea were absent. A chest radiograph showed diffuse alveolar infiltration of both lungs, without pleural effusion. Laboratory studies showed leukopenia (leukocytes = 1.66 × 10⁹/L), mild thrombocytopenia (115,000 platelets/mm³), 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.

Necropsy showed hemorrhagic foci in both lungs. 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. These lesions were characteristics of necrotizing pneumonia.

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.

Figure

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...

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. (7). The spa type was 355 and the sequence type was ST377 (Figure). 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 327–350), reverse 5´-CTT CTA CgC gCT CTC TTT TTA Ag-3´ (nt 564–586), 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).

We report the identification of a new, emerging, highly virulent PVL-positive CA-MRSA clone that harbors the SCCmec type V cassette. This tends to confirm the continuing emergence of new CA-MRSA clones. 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. (9) but must be confirmed.