Elsevier

The Lancet

Volume 359, Issue 9308, 2 March 2002, Pages 753-759
The Lancet

Mechanisms of Disease
Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients

https://doi.org/10.1016/S0140-6736(02)07877-7Get rights and content

Summary

Background

Between 1986 and 1998, eight cases of community-acquired pneumonia due to Staphylococcus aureus strains carrying the gene for the Panton-Valentine leukocidin (PVL) were recorded in France, six of which were fatal. We aimed to assess the clinical features of these eight cases, and those of other cases identified prospectively, and to compare them with the characteristics of patients with pneumonia caused by PVL-negative strains.

Methods

We compared eight retrospective and eight prospective cases of PVL-positive S aureus pneumonia with 36 cases of PVL-negative S aureus pneumonia. For all patients, we recorded age, length of hospital stay, risk factors for infection, signs and symptoms, laboratory findings, antibiotic treatment, and serial radiological findings.

Findings

Median age was 14·8 years (IQR 5·4-24·0) for the PVL-positive patients and 70·1 years (59·2-81·4) for the others (p=0·001). Influenza-like illness had occurred during the 2 days before admission in 12 of the 16 PVL-positive patients, but in only three of 33 PVL-negative patients (p<0·0001). PVL-positive infections were more often marked by: temperature greater than 39°C (p=0·01), heart rate above 140 beats per min (p=0·02), haemoptysis (p=0·005), onset of pleural effusion during hospital stay (p=0·004), and leucopenia (p=0·001). The survival rate 48 h after admission was 63% for the PVL-positive patients and 94% for PVL-negative individuals (p=0·007). Histopathological examination of lungs at necropsy from three cases of necrotising pneumonia associated with PVL-positive S aureus showed extensive necrotic ulcerations of the tracheal and bronchial mucosa and massive haemorrhagic necrosis of interalveolar septa.

Interpretation

PVL-producing S aureus strains cause rapidly progressive, haemorrhagic, necrotising pneumonia, mainly in otherwise healthy children and young adults. The pneumonia is often preceded by influenza-like symptoms and has a high lethality rate.

Introduction

Staphylococus aureus is responsible for about 2% of cases of community-acquired pneumonia1 and at least 10% of cases of nosocomial pneumonia.1, 2 Most patients with S aureus pneumonia are elderly and have serious underlying disorders such as cardiovascular disease, malignant disease, chronic pulmonary disease, and diabetes mellitus.3, 4, 5 The lethality rate ranges from 30% to 80%.3, 4

Panton-Valentine leukocidin (PVL) is an extracellular product of S aureus. PVL was detected in fewer than 5% of S aureus isolates in a general hospital.6 We have found it to be associated with primary skin infections such as furunculosis, and severe necrotising pneumonia.7 In 1998, a review of S aureus infections reported to the French Reference Centre for Staphylococcal Toxaemia (Lyon, France) between 1986 and 1998 revealed eight cases of severe community-acquired pneumonia caused by S aureus strains carrying the PVL gene, six of which were fatal.7 The patients were all immunocompetent children or young adults. All had a preceding influenza-like syndrome before developing pneumonia, and the six deaths occurred shortly after diagnosis. Necropsy showed diffuse necrotising haemorrhagic pneumonia. We investigated the clinical features and the prognosis of this illness, and compared them with those of S aureus pneumonia caused by PVL-negative strains.

Section snippets

Patients

Since 1985, S aureus strains have been sent to the French Reference Centre for Staphylococcal Toxaemia for various purposes, such as the detection of toxin production in S aureus toxin-associated diseases or severe staphylococcal suppurative infections. From this collection, a subset of 172 S aureus isolates, representative of all staphylococcal infections, was chosen in 1998 to assess the importance of PVL in various clinical syndromes.7 27 S aureus strains were associated with

Results

Preliminary analyses showed that the patients in the prospective study differed from the retrospective cases only in their lower rate of haemoptysis (p= 0·007). We therefore pooled all PVL-positive cases for subsequent analysis.

Table 1 shows the baseline characteristics of the cases of necrotising pneumonia due to PVL-positive S aureus compared with those caused by PVL-negative S aureus. PV-positive patients were younger than the others, but the median interval between symptom onset and

Discussion

Pneumonia caused by PVL-positive S aureus seems to be a specific disease entity with a poor prognosis. It occurs in otherwise healthy children and young adults and is preceded by an influenza-like syndrome. It is characterised by fever, haemoptysis, and leucopenia, and rapidly progresses to acute respiratory distress syndrome. The lethality rate is high. Because of the necrotic histopathological appearance of the lungs, we designate this illness “S aureus necrotising pneumonia”. The disease is

GLOSSARY

leukocidin
Group of bacterial toxins that kill leucocytes by creating pores in the cell membrane; as well as S aureus Panton-Valentine leukocidin, the group includes Pasteurella haemolytica leukotoxin, Actinobacillus actimycetemcomitans leukotoxin, Listeria monocytogenes listeriolysin, Escherichia coli haemolysin, and Fusobacterium necrophorum leukotoxin.
pore-forming toxin
These toxins work by inducing holes in the plasma membrane of eukaryotic cells, thus breaking the permeability barrier that

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