TY - JOUR
T1 - Preventive ceftriaxone in patients at high risk of stroke-associated pneumonia. A post-hoc analysis of the PASS trial
AU - Sluis, Wouter M.
AU - Westendorp, Willeke F.
AU - van de Beek, Diederik
AU - Nederkoorn, Paul J.
AU - van der Worp, H. Bart
N1 - Funding Information: Funding: The Preventive Antibiotics in Stroke Study was funded by The Netherlands Organization for Health Research and Development (ZonMW grant no. 171002302 to DvdB and PJN; grant no. 016116358 to DvdB), The Netherlands Heart Foundation (grant no.2009B095 to DvdB and PJN), and the European Research Council (ERC Starting Grant to DvdB). WMS is supported by the European Union’s Horizon 2020 Research and Innovation Programme (grant No. 634809). HBvdW reports grants from Stryker outside the submitted work, and served as a consultant to Bayer and LivaNova, with fees paid to his institution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this post-hoc analysis. We want to express our gratitude to everyone participating in the Preventive Antibiotics in Stroke Study. A list of centres and investigators can be found in the Supplement (S1 Table). Publisher Copyright: Copyright: © 2022 Sluis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background Infections complicate the acute phase of stroke in one third of patients and especially pneumonia is associated with increased risk of death or dependency. In randomized trials of stroke patients, preventive antibiotics reduced overall infections, but did not reduce pneumonia or improve outcome. This may be explained by broad selection criteria, including many patients with a low risk of pneumonia. To assess the potential of selection of patients at high risk of pneumonia, we performed a post-hoc analysis in the Preventive Antibiotics in Stroke Study (PASS). Methods PASS was a multicentre phase 3 trial in acute stroke patients who were randomized to preventive ceftriaxone for four days within 24 hours or standard care. For this analysis patients were divided based on the ISAN risk score for pneumonia as follows: low (0–6), medium (7–14) and high (15–21). Primary outcomes were pneumonia rate during admission as judged by the treating physician, and by an independent committee; secondary outcomes were overall infections and unfavorable outcome (modified Rankin Scale 3). We adjusted with multivariable regression for possible confounders: age, stroke subtype and severity, pre-stroke dependency and diabetes. Results Pneumonia occurred more frequently in higher risk groups (25.7% (high), 9.0% (medium) 1.5%, (low)). The absolute difference in pneumonia rate between patients treated with ceftriaxone or standard care increased with the ISAN score (low: 0.5%, medium: 1.2%, high: 10.1%). After adjustment ceftriaxone reduced overall infections in the low and medium groups, not in the high-risk group. There was a trend towards reduction of pneumonia as judged by the committee (3.7% vs 13.6%, aOR = 0.164, p = 0.063) in the high-risk group. Conclusions This post-hoc analysis of PASS confirmed higher rates of pneumonia with higher ISAN scores, and suggests that in acute stroke patients with an ISAN score of 15, preventive ceftriaxone for four days may reduce pneumonia rate.
AB - Background Infections complicate the acute phase of stroke in one third of patients and especially pneumonia is associated with increased risk of death or dependency. In randomized trials of stroke patients, preventive antibiotics reduced overall infections, but did not reduce pneumonia or improve outcome. This may be explained by broad selection criteria, including many patients with a low risk of pneumonia. To assess the potential of selection of patients at high risk of pneumonia, we performed a post-hoc analysis in the Preventive Antibiotics in Stroke Study (PASS). Methods PASS was a multicentre phase 3 trial in acute stroke patients who were randomized to preventive ceftriaxone for four days within 24 hours or standard care. For this analysis patients were divided based on the ISAN risk score for pneumonia as follows: low (0–6), medium (7–14) and high (15–21). Primary outcomes were pneumonia rate during admission as judged by the treating physician, and by an independent committee; secondary outcomes were overall infections and unfavorable outcome (modified Rankin Scale 3). We adjusted with multivariable regression for possible confounders: age, stroke subtype and severity, pre-stroke dependency and diabetes. Results Pneumonia occurred more frequently in higher risk groups (25.7% (high), 9.0% (medium) 1.5%, (low)). The absolute difference in pneumonia rate between patients treated with ceftriaxone or standard care increased with the ISAN score (low: 0.5%, medium: 1.2%, high: 10.1%). After adjustment ceftriaxone reduced overall infections in the low and medium groups, not in the high-risk group. There was a trend towards reduction of pneumonia as judged by the committee (3.7% vs 13.6%, aOR = 0.164, p = 0.063) in the high-risk group. Conclusions This post-hoc analysis of PASS confirmed higher rates of pneumonia with higher ISAN scores, and suggests that in acute stroke patients with an ISAN score of 15, preventive ceftriaxone for four days may reduce pneumonia rate.
KW - Anti-Bacterial Agents/therapeutic use
KW - Ceftriaxone/therapeutic use
KW - Humans
KW - Pneumonia/complications
KW - Stroke/complications
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85145424717&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0279700
DO - https://doi.org/10.1371/journal.pone.0279700
M3 - Article
C2 - 36584124
SN - 1932-6203
VL - 17
SP - e0279700
JO - PLOS ONE
JF - PLOS ONE
IS - 12 December
M1 - e0279700
ER -