Antibiotic Class and Outcome in Post-stroke Infections: An Individual Participant Data Pooled Analysis of VISTA-Acute

With a 30% occurrence rate post stroke, you can tell your stroke hospital's competence if they have a infection prevention protocol and an infection protocol. Or are you OK with them just 'winging it'?

Antibiotic Class and Outcome in Post-stroke Infections: An Individual Participant Data Pooled Analysis of VISTA-Acute

Craig J. Smith^1,2, Calvin Heal³, Andy Vail³, Adam R. Jeans⁴, Willeke F. Westendorp⁵, Paul J. Nederkoorn⁵, Diederik van de Beek⁵, Lalit Kalra⁶, Joan Montaner^7,8, Mark Woodhead⁹, and Andreas Meisel^10* on behalf of the VISTA Collaboration and PISCES Group

• ¹Greater Manchester Comprehensive Stroke Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom
• ²Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom
• ³Centre for Biostatistics, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
• ⁴Division of Clinical Support Services and Tertiary Medicine, Department of Microbiology, Salford Royal NHS Foundation Trust, Salford, United Kingdom
• ⁵Department of Neurology, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
• ⁶Clinical Neurosciences, King's College Hospital NHS Foundation Trust London, London, United Kingdom
• ⁷Neurovascular Research Laboratory, Vall d' Hebron Institute of Research, Barcelona, Spain
• ⁸Stroke Research Program, Department of Neurology, Institute de Biomedicine of Seville, Hospital Universitario Virgen Macarena, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain
• ⁹Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
• ¹⁰Department of Neurology, NeuroCure Clinical Research Center, Center for Stroke Research Berlin, Charité Universitaetsmedizin Berlin, Berlin, Germany

Introduction: Antibiotics used to treat post-stroke infections have differing antimicrobial and anti-inflammatory effects. Our aim was to investigate whether antibiotic class was associated with outcome after post-stroke infection.

Methods: We analyzed pooled individual participant data from the Virtual International Stroke Trials Archive (VISTA)-Acute. Patients with ischemic stroke and with an infection treated with systemic antibiotic therapy during the first 2 weeks after stroke onset were eligible. Antibiotics were grouped into eight classes, according to antimicrobial mechanism and prevalence. The primary analysis investigated whether antibiotic class for any infection, or for pneumonia, was independently associated with a shift in 90 day modified Rankin Scale (mRS) using ordinal logistic regression.

Results: 2,708 patients were eligible (median age [IQR] = 74 [65 to 80] y; 51% female; median [IQR] NIHSS score = 15 [11 to 19]). Pneumonia occurred in 35%. Treatment with macrolides (5% of any infections; 9% of pneumonias) was independently associated with more favorable mRS distribution for any infection [OR (95% CI) = 0.59 (0.42 to 0.83), p = 0.004] and for pneumonia [OR (95% CI) = 0.46 (0.29 to 0.73), p = 0.001]. Unfavorable mRS distribution was independently associated with treatment of any infection either with carbapenems, cephalosporins or monobactams [OR (95% CI) = 1.62 (1.33 to 1.97), p < 0.001], penicillin plus β-lactamase inhibitors [OR (95% CI) = 1.26 (1.03 to 1.54), p = 0.025] or with aminoglycosides [OR (95% CI) = 1.73 (1.22 to 2.46), p = 0.002].

Conclusion: This retrospective study has several limitations including effect modification and confounding by indication. Macrolides may have favorable immune-modulatory effects in stroke-associated infections. Prospective evaluation of the impact of antibiotic class on treatment of post-stroke infections is warranted.

Introduction

Infections frequently complicate stroke, occurring in up to 30% of patients, and increase the likelihood of death and unfavorable outcomes in survivors (1–3). Whilst antibiotics are the mainstay of treatment, the microbiological etiology of common infections complicating stroke, such as pneumonia or urinary tract infection, are poorly characterized. Further, there are no antibiotic treatment trials of infections complicating stroke. The effectiveness of different antibiotic classes is therefore uncertain, there is a lack of evidence to inform antibiotic guidelines (e.g., for pneumonia complicating stroke) and empirical antibiotic treatment is variable (4, 5).

Inflammatory and immune responses play a central role in the pathophysiology of stroke and associated clinical outcomes (6). Post-stroke infections exacerbate deleterious inflammatory and immune responses, which may impact further on adverse outcomes (7). Antibiotics used to treat post-stroke infections can modulate the pathophysiology of experimental stroke independent of their anti-microbial effects, by modulating inflammatory or excitotoxic pathways (8–14). Randomized trials of prophylactic antibiotics in acute stroke have failed to improve clinical outcomes or prevent pneumonia (3, 5, 15–17), and had varying effects in preventing urinary tract infections. This has raised questions about the potential effectiveness of some antibiotic classes commonly used for post-stroke infections, particularly pneumonia (18).

Taken together, these data suggest that choice of antibiotic class for post-stroke infections could have important implications for clinical outcomes. We therefore hypothesized that antibiotic class influences outcome after stroke relating to spectrum of antimicrobial coverage and to other (e.g., inflammatory) mechanisms independent of antimicrobial effects. The aim of this study was to investigate whether class of antibiotic used to treat clinically diagnosed pneumonia or any infection in the first 2 weeks after stroke was associated with clinical outcomes.

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