Prognostic factors of severe community-acquired staphylococcal pneumonia in France

Abstract

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.

Staphylococcus aureus virulence factor expression matters: input from targeted proteomics shows Panton-Valentine leucocidin impact on mortality

“…Clinical isolates and accompanying clinical data were obtained from a previously published French cohort of severe CAP [15]. The clinical features retained for the present study were those representing severity and outcome in the cohort study: death, leukopenia (defined as total leukocyte count < 3 G/L), and hemoptysis extracted from the Gillet study [15] (Table S2). The age-adapted Charlson Comorbidity Index (CCI) score was retained as a control covariate to adjust prediction models to the baseline characteristics of the patients.…”

“…Given the large diversity in the genetic background of the corresponding strains ( [15] and Table S2), the possibility that the proteome could be correlated with the genetic background was tested by principal component analysis. Neither the four accessory gene regulator (agr) types nor the 21 clonal complexes (CC) and 2 sequence types (ST) of the collection explained the proteome distribution as no proteomic profile could be associated with any of these genetic backgrounds (Figure 3).…”

“…The study showed that PVL was an independent predictor of death, hemoptysis, and leukopenia. It also found that edinB (encoding the epidermal differentiation inhibitor) was a predictor of hemoptysis and leukopenia and that the staphylococcal enterotoxin A (seA) gene predicted leukopenia [15]. We thus examined the possible association of the same severity parameters (death, hemoptysis, and leukopenia) with the proteomic data, assuming that such an analysis based on quantitative data could reveal novel associations, particularly regarding the virulence factors present in all strains.…”

Neutralization of the Staphylococcus aureus Panton-Valentine leukocidin by African and Caucasian sera

“…Given the higher incidence of SSTI in children in PVL-endemic sub-Saharan Africa [ 13 , 21 ], it could be assumed that the immature humoral immunity of children lacks protective antibodies against PVL. Indeed, in a recent study on S. aureus pneumonia almost all cases in a patient cluster under the age of three were caused by PVL-positive S. aureus [ 22 ]. Nevertheless, Hermos et al [ 23 ] reported that antibody levels against PVL were significantly elevated in children with PVL-positive methicillin-resistant S. aureus (MRSA) SSTI compared to children infected with PVL-negative MRSA or to uninfected children.…”

Lateral Flow Immunoassay for the Detection of Panton-Valentine Leukocidin in Staphylococcus aureus From Skin and Soft Tissue Infections in the United Arab Emirates

“…Global data indicates an increasing trend of incidence and severity of SSTIs caused by MRSA isolates ( Olaniyi et al., 2017 ). Panton Valentine leukocidin (PVL) is a virulence factor which is associated with S. aureus strains causing SSTI and severe forms of community acquired pneumonia ( Gosbell, 2005 ; Wannet et al., 2005 ; Yamasaki et al., 2005 ; Marazza et al., 2007 ; Masiuk et al., 2010 ; Gillet et al., 2021 ). PVL consists of two distinct components which form polymeric pores in the membranes of white blood cells which leads to cell death.…”