Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial

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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

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dc.contributor.author	Ceccato, Adrian
dc.contributor.author	Cillóniz, Catia
dc.contributor.author	Ranzani, Otavio T.
dc.contributor.author	Menéndez, Rosario
dc.contributor.author	Agustí García-Navarro, Carles
dc.contributor.author	Gabarrús, Albert
dc.contributor.author	Ferrer, Miquel
dc.contributor.author	Sibila Vidal, Oriol
dc.contributor.author	Niederman, Michael S.
dc.contributor.author	Torres Martí, Antoni
dc.date	2018-06-14T14:18:45Z
dc.date	2018-06-14T14:18:45Z
dc.date	2017-06-15
dc.date	2018-06-14T14:18:45Z
dc.identifier	1932-6203
dc.identifier	675109
dc.identifier	2870445
dc.identifier	28617807
dc.identifier.uri	http://hdl.handle.net/2445/122964
dc.description	Background: Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial. Methods: We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL) who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone) and corticosteroid arm (placebo or corticosteroids). The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure). Results: The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI) risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374); however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31%) vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24%) vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0%) vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009). We found a significant difference for In-hospital mortality in the per protocol population (overall p = 0.01). We did not find significant differences in treatment failure, early or late; or In-hospital mortality after adjusting for severity (PSI), year and centre of enrolment. Conclusions: In this exploratory analysis, we observed that the glucocorticosteroids and macrolides combination had no statistically significant association with main clinical outcomes compared with other combinations in patients with severe community acquired pneumonia and a high inflammatory response after taking account potential confounders.
dc.format	14 p.
dc.format	application/pdf
dc.language	eng
dc.publisher	Public Library of Science (PLoS)
dc.relation	Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0178022
dc.relation	PLoS One, 2017, vol. 12, num. 6, p. e0178022
dc.relation	https://doi.org/10.1371/journal.pone.0178022
dc.rights	cc-by (c) Ceccato, Adrian et al., 2017
dc.rights	http://creativecommons.org/licenses/by/3.0/es
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Pneumònia
dc.subject	Antibiòtics
dc.subject	Pneumonia
dc.subject	Antibiotics
dc.title	Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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