Reassessment of the cooperativity between efflux system MexAB-OprM and cephalosporinase AmpC in the resistance of Pseudomonas aeruginosa to β-lactams

• Published in: Journal of antimicrobial chemotherapy Vol. 76; no. 2; pp. 536 - 539
• Main Authors: Grosjean, Mélanie, Tazrout, Sara, Bour, Maxime, Triponey, Pauline, Muller, Cédric, Jeannot, Katy, Plésiat, Patrick
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 19-01-2021; Oxford University Press (OUP)
• Subjects: Life Sciences; Microbiology and Parasitology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkaa462

Purpose Staphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotising pneumonia in older patients. Methicillin resistance and the Panton–Valentine leukocidin (PVL) toxin, as well as less specific factors, have been associated with poor outcome in severe CAP, but their roles are unclear. Methods A 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 (least absolute shrinkage and selection operator) regressions. Results Out of 163 included patients, aged 1 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 (three (15%) out of 19) compared to PVL-positive CAP in older patients (31 (47%) out of 66). Mortality in older patients was predicted by PVL-positivity (hazard ratio (HR) 1.81, 95% CI 1.03–3.17) and methicillin resistance (HR 2.37, 95% CI 1.29–4.34) independently from S. aureus lineages and the presence of other determinants of virulence. 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, S. aureus genetic background and other virulence factors.