Skip Navigation

Factors Predicting Mortality in Necrotizing Community-Acquired Pneumonia Caused by Staphylococcus aureus Containing Panton-Valentine Leukocidin

  1. Yves Gillet1,2,3,
  2. Philippe Vanhems1,3,4,
  3. Gerard Lina1,2,3,
  4. Michèle Bes1,2,3,
  5. François Vandenesch1,2,3,
  6. Daniel Floret1,3, and
  7. Jerome Etienne1,2,3
  1. 1Université de Lyon 1, Centre National de Référence des Staphylocoques, Lyon
  2. 2Inserm U851, Faculté Laennec, Centre National de Référence des Staphylocoques, Lyon
  3. 3Hospices Civils de Lyon, H<circ;pital Edouard Herriot, Lyon
  4. 4Unité Mixte de Recherche, Centre National de la Recherche Scientifique 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France
  1. Reprints or correspondence: Dr. Jerome Etienne, Université de Lyon, Inserm U851, Faculté de Médecine Laennec, 7 rue Guillaume Paradin, 69372 Lyon, Cedex 08, France (jetienne{at}univ-lyon1.fr).
 
Next Section

Abstract

Background. Necrotizing pneumonia due to Panton-Valentine leukocidin–producing strains of Staphylococcus aureus is associated with a high mortality rate. We sought factors associated with vital outcome in 50 cases occurring from 1986 through 2005.

Methods. We compared the clinical and biological characteristics of 50 patients according to their vital outcome and examined the characteristics of the corresponding S. aureus isolates.

Results. The overall mortality rate was 56%, and the median survival time was 10 days. All of the deaths were attributed to S. aureus infection and were secondary to refractory shock and/or respiratory failure. Fatal outcome was associated with classical severity factors, such as the need for mechanical ventilation or inotrope support, and with onset of the acute respiratory distress syndrome. Airway bleeding was strongly associated with fatal outcome (P = .002). Patients who had focal staphylococcal infection before the onset of pneumonia had a significantly lower mortality rate (P = .002). The main biological feature associated with death was leukopenia (P <t; .001). In multivariate analysis, leukopenia and erythroderma occurring within the first 24 h after admission to the hospital were independently associated with fatal outcome. Erythroderma was not associated with toxic shock syndrome toxin.

Conclusions. Airway bleeding, erythroderma, and leukopenia are associated with fatal outcome from Panton-Valentine leukocidin–positive S. aureus necrotizing pneumonia. More work is needed to develop more efficacious therapy against this highly lethal disease.

Staphylococcus aureus expresses a variety of virulence factors, including Panton-Valentine leukocidin (PVL), a cytotoxin. PVL is expressed by major methicillin-resistant S. aureus clones, which have now spread throughout the world [1]. PVL is specifically associated with primary skin and soft-tissue infections and causes severe necrotizing pneumonia through its direct toxic activity and the indirect up-regulation of surface proteins [2,3–4]. Necrotizing S. aureus pneumonia has long been recognized, but the association with PVL was made in 2002 [2], and numerous cases have since been reported worldwide [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23–24]. Contrary to PVL-negative S. aureus pneumonia, PVL-positive S. aureus pneumonia is often preceded by influenza-like symptoms and is mainly characterized by hemoptysis, pleural effusion, rapid onset of acute respiratory distress, and leukopenia [2].

PVL-positive S. aureus necrotizing pneumonia is associated with a high fatality rate. Among 41 cases reported in the literature, 25 patients (61%) died, usually rapidly [2, 6, 7, 9,10,11,12,13,14,15,16–17, 19,20,21,22,23–24]. No independent factors associated with vital outcome have thus far been described. We examined 50 cases of PVL-associated necrotizing pneumonia that were reported from 1986 through 2005 to identify determinants of vital outcome.

Previous SectionNext Section

Patients and Methods

Since completing the first study of 16 cases of PVL-associated necrotizing pneumonia [2], we have prospectively collected case reports of documented S. aureus pneumonia caused by strains shown by the French National Reference Center for Staphylococci (Lyon, France) to harbor the PVL genes (luk-PV). All of these cases were spontaneously referred to the Reference Center by hospitals in France and elsewhere, and only minimal clinical data were provided in most cases. When the case matched the inclusion criteria (see below), a standardized data collection form was immediately sent to the referring clinician. The diagnostic criteria for community-acquired pneumonia were those used in the above-mentioned princeps study [2].

Definitions. Pneumonia was defined by signs and symptoms of lower respiratory tract infection (e.g., cough, expectoration, and chest pain) and pulmonary infiltrates on the chest radiograph that were not attributable to other causes, coinciding with isolation of S. aureus as the only potential pathogen, by at least 1 of the following procedures: (1) puncture of a pleural effusion or lung abscess; (2) culture of bronchoalveolar lavage fluid (⩾104 CFU/mL), Wimberley brushing (⩾103 CFU/mL), or protected tracheal aspiration (⩾103 CFU/mL); and (3) blood culture yielding the same S. aureus strain as that found in tracheal secretions. Pneumonia was classified as nosocomial when respiratory symptoms started at least 48 h after hospitalization, and all such cases were excluded from the study.

Microbiological studies. S. aureus isolates were tested for toxin production and antimicrobial susceptibility. Gene sequences encoding PVL and superantigenic toxins (e.g., enterotoxins A–C and toxic shock syndrome toxin–1) were detected using PCR-based methods [25]. Isolates were tested for antimicrobial susceptibility by broth microdilution, using the interpretive criteria of the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) [26]. The following antimicrobial agents were tested: penicillin, oxacillin, kanamycin, tobramycin, gentamicin, erythromycin, clindamycin, tetracycline, ofloxacin, fusidic acid, rifampin, vancomycin, teicoplanin, fosfomycin, trimethoprim-sulfamethoxazole, and linezolid. In addition, the mecA gene, which codes for methicillin resistance, was detected by PCR, as described elsewhere [27]. Only cases caused by PVL-positive S. aureus strains were included in the study.

Data. The following data were recorded in each case: demographic data, medical history (including risk factors for infection and history of personal or familial abscesses or furuncles), signs and symptoms, radiological findings, and laboratory results during the first 48 h of hospitalization. Severity was rated using the Pediatric Risk of Mortality (PRISM) 3 score [28] for patients aged <t;18 years and using the Simplified Acute Physiology Score (SAPS) II [29] for patients aged ⩾18 years, when available. Some biological or radiological results were missing because of death shortly after admission to the hospital.

Statistical analysis. The population was subdivided into patients who survived and patients who died in the hospital. Baseline characteristics of the 2 subgroups were compared with the χ2 test or Fisher's exact test for categorical variables and Student's t test or the Mann-Whitney U test for continuous variables.

The endpoint was death of all causes, and the survival probability was estimated using the Kaplan-Meier method. Baseline was the day of admission to the hospital for pneumonia, and patients who survived were censored at discharge from the hospital. When patients died within 24 h after admission, the observation period was rounded to 1 day. Survival distributions were compared with the log-rank test. Variables independently associated with survival were identified with a Cox regression model based on hazard ratios. Variables with P values from .10 through .15 were entered in a multivariate model. P values <t;.05 (2-tailed) were considered to indicate statistical significance. Statistical analyses were performed using SPSS software, version 11.0 (SPSS).

Previous SectionNext Section

Results

Fifty-seven case reports of PVL-positive S. aureus pneumonia were collected from 39 different hospitals, but 7 case reports were excluded because of missing data. No cases of hospital-acquired necrotizing pneumonia were reported and excluded during the study. Therefore, the study involved 50 cases (table 1). The cases occurred in France (32 cases), French Polynesia (10 cases), the French West Indies (2 cases), and the United States (2 cases), as well as in Algeria, Germany, Singapore, and Switzerland (1 case each). The male-to-female sex ratio was 1.3 (28 males and 22 females), and the median age was 14.5 years (interquartile range [IQR], 1.8–36 years).

Figure 1
Figure 1

Probability of survival among patients with Panton-Valentine leukocidin–positive Staphylococcus aureus pneumonia, according to airway bleeding.

Table 1
Table 1

Baseline characteristics of 50 patients with Panton-Valentine leukocidin–positive Staphylococcus aureus pneumonia.

Medical History

Risk factors for infection and/or respiratory disease were identified in 20% of patients. The most frequent risk factor was smoking, which was reported for 7 patients and was associated with alcohol abuse for 2 patients. Common risks factors for staphylococcal infection, such as diabetes, steroid therapy, and immunosuppressive drug therapy, were recorded for only 1 patient each. Among the 34 patients for whom data were available, 6 (17.6%) had a personal history of furuncles or skin abscess, and another patient had a history of familial furunculosis.

Presentation

The median duration of symptoms before hospitalization was 3.0 days (IQR, 2.0–5.0 days). Influenza-like symptoms occurred before hospital admission in 33 (67.3%) of 49 patients. Virological tests were performed for 9 patients: 4 patients had influenza type A infection, 1 had cytomegalovirus infection, and 4 had negative results. Twelve patients (24%) had preexisting focal staphylococcal infections, which consisted of skin abscesses in 6 patients, deep abscesses in 4 patients, and both skin and deep abscesses in 2 patients. Four of the 6 patients with skin abscesses only had previously had furuncles, and the other 2 patients had no known history of skin infections. None of the 4 patients with deep abscesses only had previously had skin infections or abscesses.

The clinical course during the first 48 h after hospital admission was usually severe, as reflected by the severity scores (PRISM 3 or SAPS II), which were available at admission for 31 patients. The median SAPS II value was 53.5 (IQR, 28.0–72.0), and the median PRISM 3 value was 15 (IQR, 5.8–20.5). Fever (temperature, >39°C) was reported in 38 (76%) of 50 patients. The most remarkable feature was airway bleeding, which was present in 22 (44%) of 50 patients. The lower airways were involved in 21 patients (presenting with hemoptysis or bloody tracheal aspirate), 4 of whom also experienced nasal hemorrhage. One patient experienced only nasal hemorrhage.

Most patients had marked respiratory distress, and 39 (78%) of 50 patients required intubation and mechanical ventilation. The severity of respiratory failure was reflected by the low PaO2 : FiO2 ratio in intubated patients (median PaO2 : FiO2 ratio, 69; IQR, 47.5–103.3). Generalized rash was present in 5 (10.4%) of 48 patients, and 8 patients (17%) had diarrhea.

Chest radiographic examination was performed for only 48 of 50 patients, because 2 patients died very shortly after hospital admission. The radiographs showed multilobar consolidation in 38 (79.1%) of 48 patients and unilobar consolidation in 9 (18.1%) of 48 patients. Pleural effusion was associated with consolidation in 24 (50%) of 48 patients and was isolated in 1 patient (2%). Bubbles, excavation, and pyopneumothorax were reported in 4, 2, and 2 patients, respectively.

Biological Features

Because of the rapid death of 2 patients, biological data were available for only 48 patients. The median minimal leukocyte count during the first 48 h of hospitalization was 3900 leukocytes/mL (IQR, 1230–10,700 leukocytes/mL), and 26 (54.1%) of 48 patients had a leukocyte count <t;5000 leukocytes/mL. The minimal platelet count was also low, with a median of 145,000 platelets/mL (IQR, 50,000–242,000 platelets/mL); 10 (21.2%) of 47 patients had a platelet count <t;50,000 platelets/mL.

S. aureus was recovered by blood culture in 31 (62%) of 50 patients, in pleural fluid from 15 (30%) of 50 patients, and in bronchoalveolar lavage fluid or brushing specimens from 17 (34%) of 50 patients. All S. aureus isolates were fully characterized. Six (12%) of the 50 isolates were methicillin resistant. Methicillin resistance was always associated with kanamycin resistance. Thirteen isolates were resistant to tetracycline, 9 to erythromycin, 6 to trimethoprim-sulfamethoxazole, 6 to fusidic acid, and 3 to tobramycin. Resistance to gentamicin, clindamycin, ofloxacin, and rifampin was sporadic. All isolates were susceptible to glycopeptides, fosfomycin, and linezolid. In addition to the presence of the luk-PV genes encoding PVL, 11 isolates harbored at least 1 of the toxin genes associated with nonmenstrual toxic shock syndrome; sea (encoding SEA), seb (encoding SEB), and sec (encoding SEC) were detected in 6 isolates, 5 isolates, and 1 isolate, respectively. The tst gene (encoding toxic shock syndrome toxin–1) was not detected in any isolate.

Treatment and Outcome

Intubation and mechanical ventilation were required for 39 (78%) of 50 patients (table 1). Among the patients who survived, the median duration of mechanical ventilation was 6.5 days. The frequencies of other treatments are given for 48 patients, because 2 patients died before receiving any other treatment.

Antibiotic therapy was initiated on the first hospital day in 45 of 48 patients. During the first 24 h, at least 1 of the prescribed drugs was active against S. aureus in 37 (82.2%) of 45 patients. Among the 11 patients in whom initial antibiotic treatment was inappropriate or absent, active antibiotics were introduced between 24 and 72 h to 5 patients and after 72 h to 2 patients; the remaining 4 patients died without receiving appropriate antibiotic treatment. High-dose intravenous immunoglobulins were administered to 2 patients who survived but presented with the main features associated with death.

Respiratory status was characterized by the onset of signs consistent with acute respiratory distress syndrome with diffuse bilateral infiltrates in 24 (51.1%) of 47 patients. In addition to the 25 patients who initially had pleural effusion, 4 patients developed purulent pleural effusion after hospital admission. Serial radiological studies were not available for 3 patients because of early death.

The overall in-hospital mortality rate was 56%, and the median survival time was 10 days. All of the deaths were attributed to S. aureus infection and were secondary to refractory shock and/or respiratory failure.

Factors Associated with Vital Outcome

Clinical characteristics. The need for artificial ventilation or inotrope support and acute respiratory distress syndrome onset were associated with death. Airway bleeding was strongly associated with fatal outcome and was also associated with more rapid death (figure 1). All 5 of the patients who developed erythroderma within 24 h after hospital admission died, and erythroderma never occurred in the patients who survived (P = .059).

Features associated with survival included probable hematogenous infection of the lungs from a focus of infection (such as skin abscesses or deep abscesses). The presence of pleural effusion at hospital admission was also associated with survival. The mortality rate was significantly higher among female patients.

Biological factors. The main biological feature associated with death was leukopenia (table 2). The platelet count was also lower in patients who died but was not markedly below the normal limit. The PaO2 : FiO2 ratio in patients receiving mechanical ventilation was low in both patients who survived and patients who died, but it was significantly lower in patients who died.

Table 2
Table 2

Comparison of patients who survived with patients who died.

Multivariate analysis. Multivariate analysis revealed that the only factors independently associated with fatal outcome were onset of leukopenia and erythroderma within 24 h after hospital admission (table 3).

Table 3
Table 3

Multivariate analysis of factors associated with death among patients with Panton-Valentine leukocidin–positive Staphylococcus aureus pneumonia.

Previous SectionNext Section

Discussion

In this series of 50 cases of necrotizing pneumonia, the overall mortality rate was slightly lower than that in the initial study [2]—probably because of better diagnosis and treatment—but was, nonetheless, very high (overall mortality rate, 56%), especially considering that most of the patients were young, immunocompetent, and otherwise healthy.

Factors associated with fatal outcome. In univariate analysis, the need for inotrope support, onset of acute respiratory distress syndrome, a low PaO2 : FiO2 ratio, and high severity scores were associated with fatal outcome, but these characteristics are generally found in studies of severe infectious respiratory diseases. In contrast, hemoptysis, which is uncommon in children and adolescents with severe pneumonia, occurred very frequently in our series (in 44% of patients) and was associated with rapid death [figure 1]. Thus, hemoptysis appears to be both a major diagnostic sign of necrotizing pneumonia and an important predictor of fatal outcome. Airway hemorrhage, in this context, likely reflects necrosis of the respiratory mucosa as a consequence of the direct toxic effect of PVL, coupled with the indirect up-regulation of the lung proinflammatory factor protein A [4].

Erythroderma occurred in only 10% of the patients, but it is noteworthy that all 5 of the patients with erythroderma died. This could have occurred because staphylococcal toxic shock syndrome–related toxins, such as enterotoxins SEA, SEB, and SEC [30], and the corresponding toxin genes were detected in 11 isolates. However, only 2 of the isolates from the 5 patients with rash harbored these toxin genes, and several patients whose isolates contained these toxin genes remained free of cutaneous disorders.

With regard to biological data, leukopenia was independently associated with mortality in multivariate analysis. Not only was there a significant difference in the median leukocyte count between patients who survived and patients who died, but the relation between the leukocyte count and the risk of death appeared to be linear: the survival rate was <t;10% when the leukocyte count was <t;1000 leukocytes/mL and exceeded 85% when the leukocyte count was >10,000 leukocytes/mL. The leukocyte count was ⩽5000 leukocytes/mL in 35 patients and >15,000 leukocytes/mL in only 7 patients. This suggests that leukopenia is a specific feature of staphylococcal necrotizing pneumonia and that it is strongly associated with fatal outcome. This is in agreement with in vitro data showing that PVL induces both apoptosis and necrosis of human leukocytes [31].

Features and outcome of the disease. Initial influenza-like symptoms were present in 75% of the patients in the princeps study [2] and in 67% of the patients in the present study; no correlation was detected between influenza seasons and occurrence of necrotizing pneumonia cases. Viral infections were reported for only 5 patients, but only 9 patients had virological studies performed. Viral infections of the respiratory tract are known to facilitate the onset of bacterial pneumonia, both by impairing local defenses and by enhancing bacterial adhesion to damaged epithelia [32].

The initial presentation was always severe, with marked respiratory distress, hypoxemia, high fever, and extensive bilateral consolidations often associated with pleural effusion on chest radiography. Most of our patients received aggressive treatment, with 78% of patients receiving mechanical ventilation. Antibiotic therapy was started promptly after hospital admission and, based on in vitro activity, the initial antibiotics (those started during the first 24 h after admission) were effective against the S. aureus isolate in 82.2% of the patients. However, there was no difference between patients who survived and patients who died with regard to the in vitro efficacy of initial antibiotic therapy, suggesting that fatal outcome was not due to antibiotic treatment failure.

A personal history of furuncles appears to be protective. Unfortunately, this information was only available for 34 of the 50 patients, and the difference between patients who survived and patients who died did not reach statistical significance (27.8% of patients who survived and 6.3% of patients who died had a personal history of furuncles; P = .18). It is conceivable that patients with such a history had previously been exposed to PVL and had developed a degree of protective immunity, because anti-PVL antibodies found in human immunoglobulin preparations have been found to neutralize the action of the toxin [33].

Certain limitations of this study need to be addressed. Patient recruitment might have been biased toward hospitals specializing in pediatric infectious diseases. Certain data were lacking when death occurred shortly after hospital admission, meaning that strong early predictors may not have been available in some cases. Another limitation is a potential selection bias if the characteristics of patients are hospital-dependent and, then, if the documentation of cases (or quality of information) is related to the hospital. However, no major differences in the frequency of missing data were found among the participating hospitals.

Previous SectionNext Section

Acknowledgments

We thank David Young, for editing the manuscript, and the following clinicians for sending clinical information: C. Alonso-Tarres (de la Creu Roja Hospital, Barcelona, Spain); M. Auburtin (Bichat-Claude Bernard Hospital, Paris, France); H. Ben Mansour (Institut Montsouris, Paris, France); J. C. Berthier (Debrousse Hospital, Lyon, France); E. Bonnieux, M. P. de Barthez, V. Boussaud, M. Levy, M. Papouin-Rauzy, and V. Quenee (Centre Hospitalier Territorial de Polynésie, Papeete, French Polynesia); C. P. Cartwright (Hennepin County Medial Center, Minneapolis, MN); M. Chalumeau (Saint Vincent de Paul Hospital, Paris, France); J. Cotting (CHU Vaudois, Lausanne, Switzerland); J. L. Daigre and F. Joly (St. Laurent du Maroni Hospital, St. Laurent du Maroni, French Guyana); O. Delastre (Centre Hospitalier d'Elboeuf, Elboeuf, France); Y. Domart (Centre Hospitalier de Compi<grave;gne, Compi<grave;gne, France); B. François (Dupuytren Hospital, Limoges, France); D. Gendrel (Saint Vincent de Paul Hospital, Paris, France); W. Hamis, N. Ramdani, and M. Tazir (Mustapha Pacha Hospital, Algiers, Algeria); F. Hornig, B. Kahl, and C. von Eiff (Universitatsklinikum, Muenster, Germany); P. Hubert (Necker Enfants Malades Hospital, Paris, France); V. Jounieaux (Centre Hospitalier Sud, Amiens, France); A. Lahlou (Hautepierre Hospital, Strasbourg, France); E. Laporte-Turpin (H<circ;pital des Enfants, Toulouse, France); H. Le Loch, H. Mentec, and J. P. Sollet (Victor Dupouy Hospital, Argenteuil, France); F. Leclerc (Jeanne de Flandre Hospital, Lille, France); M. Lorrot (Robert Debré Hospital, Paris, France); B. Melon (Francois Mitterand Hospital, Pau, France); A. Metton (Georges Pianta Hospital, Thonon-les-Bains, France); F. Molenat (Centre Hospitalier, Aix-en-Provence, France); J. M. Perez (Centre Hospitalier, Pointe-<grave;-Pitre, French West Indies); D. Plantaz (Hospital de la Tronche, Grenoble, France); A. Reynaud (H<circ;tel-Dieu, Nantes, France); A. Rousson (Debrousse Hospital, Lyon, France); P. Schoeffler (H<circ;tel-Dieu, Clermont-Ferrand, France); B. Spellerberg (University of Ulm, Ulm, Germany); and L. Y. Hsu (Singapore General Hospital, Singapore City, Singapore).

Potential conflicts of interest. All authors: no conflicts.

  • Received February 2, 2007.
  • Accepted April 18, 2007.
Previous Section
 

References

  1. ↵
    1. Vandenesch F,
    2. Naimi T,
    3. Enright MC,
    4. et al
    . Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 2003;9:978-84.
    MedlineWeb of Science
  2. ↵
    1. Gillet Y,
    2. Issartel B,
    3. Vanhems P,
    4. et al
    . Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 2002;359:753-9.
    CrossRefMedlineWeb of Science
  3. ↵
    1. Lina G,
    2. Piemont Y,
    3. Godail-Gamot F,
    4. et al
    . Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections pneumonia. Clin Infect Dis 1999;29:1128-32.
    Abstract/FREE Full Text
  4. ↵
    1. Labandeira-Rey M,
    2. Couzon F,
    3. Boisset S,
    4. et al
    . Staphylococcus aureus Panton Valentine leukocidin causes necrotizing pneumonia. Science 2007;315:1130-3.
    Abstract/FREE Full Text
  5. ↵
    1. van der Flier M,
    2. van Dijk NB,
    3. Fluit AC,
    4. Fleer A,
    5. Wolfs TF,
    6. van Gestel JP
    . Fatal pneumonia in an adolescent due to community-acquired methicillin-resistant Staphylococcus aureus positive for Panton-Valentine leukocidin. Ned Tijdschr Geneeskd 2003;147:1076-9.
    Medline
  6. ↵
    1. Miyashita T,
    2. Shimamoto Y,
    3. Nishiya H,
    4. et al
    . Destructive pulmonary embolism in a patient with community-acquired staphylococcal bacteremia. J Infect Chemother 2002;8:99-102.
    Medline
  7. ↵
    1. Osterlund A,
    2. Kahlmeter G,
    3. Bieber L,
    4. Runehagen A,
    5. Breider JM
    . Intrafamilial spread of highly virulent Staphylococcus aureus strains carrying the gene for Panton-Valentine leukocidin. Scand J Infect Dis 2002;34:763-4.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Thomas P,
    2. Riffelmann M,
    3. Schweiger B,
    4. Dominik S,
    5. von Konig CH
    . Fatal influenza A virus infection in a child vaccinated against influenza. Pediatr Infect Dis J 2003;22:201-2.
    CrossRefMedlineWeb of Science
  9. ↵
    1. Klein JL,
    2. Petrovic Z,
    3. Treacher D,
    4. Edgeworth J
    . Severe community-acquired pneumonia caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom. Intensive Care Med 2003;29:1399.
    CrossRefMedlineWeb of Science
  10. ↵
    1. Hsu LY,
    2. Koh TH,
    3. Anantham D,
    4. Kurup A,
    5. Chan KP,
    6. Tan BH
    . Panton-Valentine leukocidin-positive Staphylococcus aureus, Singapore. Emerg Infect Dis 2004;10:1509-10.
    MedlineWeb of Science
  11. ↵
    1. Francis JS,
    2. Doherty MC,
    3. Lopatin U,
    4. et al
    . Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis 2005;40:100-7.
    Abstract/FREE Full Text
  12. ↵
    1. Obed A,
    2. Schnitzbauer AA,
    3. Bein T,
    4. Lehn N,
    5. Linde HJ,
    6. Schlitt HJ
    . Fatal pneumonia caused by Panton-Valentine leucocidine-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA) transmitted from a healthy donor in living-donor liver transplantation. Transplantation 2006;81:121-4.
    CrossRefMedlineWeb of Science
  13. ↵
    1. Alonso-Tarres C,
    2. Villegas ML,
    3. de Gispert FJ,
    4. Cortes-Lletget MC,
    5. Rovira Plarromani A,
    6. Etienne J
    . Favorable outcome of pneumonia due to Panton-Valentine leukocidin-producing Staphylococcus aureus associated with hematogenous origin absence of flu-like illness. Eur J Clin Microbiol Infect Dis 2005;24:756-9.
    CrossRefMedlineWeb of Science
  14. ↵
    1. Gonzalez BE,
    2. Hulten KG,
    3. Dishop MK,
    4. et al
    . Pulmonary manifestations in children with invasive community-acquired Staphylococcus aureus infection. Clin Infect Dis 2005;41:583-90.
    Abstract/FREE Full Text
  15. ↵
    1. Torell E,
    2. Molin D,
    3. Tano E,
    4. Ehrenborg C,
    5. Ryden C
    . Community-acquired pneumonia bacteraemia in a healthy young woman caused by methicillin-resistant Staphylococcus aureus (MRSA) carrying the genes encoding Panton-Valentine leukocidin (PVL). Scand J Infect Dis 2005;37:902-4.
    CrossRefMedlineWeb of Science
  16. ↵
    1. Al-Tawfiq JA,
    2. Aldaabil RA
    . Community-acquired MRSA bacteremic necrotizing pneumonia in a patient with scrotal ulceration. J Infect 2005;51:e241-3.
    CrossRefMedline
  17. ↵
    1. Frazee BW,
    2. Salz TO,
    3. Lambert L,
    4. Perdreau-Remington F
    . Fatal community-associated methicillin-resistant Staphylococcus aureus pneumonia in an immunocompetent young adult. Ann Emerg Med 2005;46:401-4.
    CrossRefMedlineWeb of Science
  18. ↵
    1. Micek ST,
    2. Dunne M,
    3. Kollef MH
    . Pleuropulmonary complications of Panton-Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production. Chest 2005;128:2732-8.
    Abstract/FREE Full Text
  19. ↵
    1. Tseng MH,
    2. Wei BH,
    3. Lin WJ,
    4. et al
    . Fatal sepsis necrotizing pneumonia in a child due to community-acquired methicillin-resistant Staphylococcus aureus: case report literature review. Scand J Infect Dis 2005;37:504-7.
    CrossRefMedlineWeb of Science
  20. ↵
    1. McAdams RM,
    2. Mazuchowski E,
    3. Ellis MW,
    4. Rajnik M
    . Necrotizing staphylococcal pneumonia in a neonate. J Perinatol 2005;25:677-9.
    CrossRefMedline
  21. ↵
    1. Boussaud V,
    2. Parrot A,
    3. Mayaud C,
    4. et al
    . Life-threatening hemoptysis in adults with community-acquired pneumonia due to Panton-Valentine leukocidin-secreting Staphylococcus aureus. Intensive Care Med 2003;29:1840-3.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Garnier F,
    2. Tristan A,
    3. Francois B,
    4. et al
    . Pneumonia new methicillin-resistant Staphylococcus aureus clone. Emerg Infect Dis 2006;12:498-500.
    MedlineWeb of Science
  23. ↵
    1. Laifer G,
    2. Frei R,
    3. Adler H,
    4. Fluckiger U
    . Necrotising pneumonia complicating a nasal furuncle. Lancet 2006;367:1628.
    CrossRefMedlineWeb of Science
  24. ↵
    1. Monaco M,
    2. Antonucci R,
    3. Palange P,
    4. Venditti M,
    5. Pantosti A
    . Methicillin-resistant Staphylococcus aureus necrotizing pneumonia. Emerg Infect Dis 2005;11:1647-8.
    MedlineWeb of Science
  25. ↵
    1. Jarraud S,
    2. Mougel C,
    3. Thioulouse J,
    4. et al
    . Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), human disease. Infect Immun 2002;70:631-41.
    Abstract/FREE Full Text
  26. ↵
    1. National Committee for Clinical Laboratory Standards
    . Performance standards for antimicrobial susceptibility testing: 14th informational supplement M100-S14. Wayne PA: National Committee for Clinical Laboratory Standards; 2004.
  27. ↵
    1. Murakami K,
    2. Minamide W,
    3. Wada K,
    4. Nakamura E,
    5. Teraoka H,
    6. Watanabe S
    . Identification of methicillin-resistant strains of staphylococci by polymerase chain reaction. J Clin Microbiol 1991;29:2240-4.
    Abstract/FREE Full Text
  28. ↵
    1. Pollack MM,
    2. Patel KM,
    3. Ruttimann UE
    . PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med 1996;24:743-52.
    CrossRefMedlineWeb of Science
  29. ↵
    1. Le Gall JR,
    2. Lemeshow S,
    3. Saulnier F
    . A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270:2957-63.
    Abstract/FREE Full Text
  30. ↵
    1. McCormick JK,
    2. Yarwood JM,
    3. Schlievert PM
    . Toxic shock syndrome bacterial superantigens: an update. Annu Rev Microbiol 2001;55:77-104.
    CrossRefMedlineWeb of Science
  31. ↵
    1. Genestier AL,
    2. Michallet MC,
    3. Prevost G,
    4. et al
    . Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria induces Bax-independent apoptosis of human neutrophils. J Clin Invest 2005;115:3117-27.
    CrossRefMedlineWeb of Science
  32. ↵
    1. de Bentzmann S,
    2. Tristan A,
    3. Etienne J,
    4. Brousse N,
    5. Vandenesch F,
    6. Lina G
    . Staphylococcus aureus isolates associated with necrotizing pneumonia bind to basement membrane type I IV collagens laminin. J Infect Dis 2004;190:1506-15.
    Abstract/FREE Full Text
  33. ↵
    1. Gauduchon V,
    2. Cozon G,
    3. Vandenesch F,
    4. et al
    . Neutralization of Staphylococcus aureus Panton Valentine leukocidin by intravenous immunoglobulin in vitro. J Infect Dis 2004;189:346-53.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (2007) 45 (3): 315-321. doi: 10.1086/519263
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most