PurposeStaphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotising pneumonia in older patients. Methicillin resistance, the Panton-Valentine leukocidin (PVL) toxin, as well as less specific factors have been associated with poor outcome in severe CAP, but their respective roles are unclear.MethodsA prospective multicentre cohort study of severe staphylococcal CAP was conducted in 77 paediatric and adult intensive care units in France between January 2011 and December 2016. After age-clustering, risk factors for mortality, including pre-existing conditions, clinical presentation, laboratory features, strain genetic lineage, PVL, other virulence factors, and methicillin resistance were assessed using univariate and multivariable Cox and LASSO regressions.ResultsOf 163 included patients, aged one month to 87 years, 85 (52.1%) had PVL-positive CAP; there were 20 (12.3%) patients aged <3 years (hereafter “toddlers”), among whom 19 (95%) had PVL-positive CAP. The features of PVL-positive CAP in toddlers matched with the historical description of staphylococcal pleuropneumonia, with a lower mortality (n=3/19, 15%) compared to PVL-positive CAP in older patients (n=31/66, 47%). Mortality in older patients was independently predicted by PVL-positivity (hazard ratio 1.81, 95% CI, 1.03 to 3.17) and methicillin resistance (2.37, 95% CI 1.29 to 4.34) independently from S. aureus lineages and the presence of other virulence determinants.ConclusionPVL was associated with staphylococcal pleuropneumonia in toddlers and was a risk factor for mortality in older patients with severe CAP, independently of methicillin resistance, S. aureus genetic background and other virulence factors.
The CT-based method increased sensitivity and did not diminish specificity, compared with the ungated method. It was more efficient than the ungated method for imaging the lower lobes and smallest lesions, which are most affected by respiratory motion.
Background
Staphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotizing pneumonia in older patients. Methicillin resistance and the Panton-Valentine leukocidin (PVL) toxin have both been associated with poor outcome in severe CAP, but their respective roles are unclear.
Methods
Prospective multicenter cohort study of severe staphylococcal CAP conducted in 77 pediatric and adult intensive care units in France between January 2011 and December 2016. Clinical features and outcomes were compared between toddlers (<3 years of age) and older patients with PVL-positive CAP; and between older patients with PVL-negative or PVL-positive CAP. Risk factors for mortality were identified using multivariate Cox regression.
Results
Of 163 included patients, aged one month to 87 years, 85 (52.1%) had PVL-positive CAP; there were 20 (12.3%) toddlers, among whom 19 (95%) had PVL-positive CAP. The features of PVL-positive CAP in toddlers matched with the historical description of staphylococcal pleuropneumonia, with a lower mortality (n = 3/19, 15%) compared to PVL-positive CAP in older patients (n=31/66, 47%). Mortality in older patients was independently predicted by PVL-positivity (hazard ratio 1.81, 95% CI, 1.03 to 3.17) and methicillin resistance (2.37, 95% CI 1.29 to 4.34). As genetic diversity was comparably high in PVL-positive and PVL-negative isolates, confounding by microbial population structure was unlikely.
Conclusion
PVL was associated with staphylococcal pleuropneumonia in toddlers and was a risk factor for mortality in older patients with severe CAP, independently of methicillin resistance. Funded by the French ministry of Health (PHRC 2010-A01132-37)
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