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

Abstract

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.

Microbiome and ischemic stroke: A systematic review

“…In fact, antibiotics treatments have been given to the cases with ischemic stroke for post-stroke infections. A total of three meta-analyses have shown that preventive antibiotic treatment after stroke onset can reduce the infections of post-stroke cases significantly, including the urinary tract infections [ 35 ] and pneumonia [ 36 ]. Nonetheless, none of these studies reported that the use of antibiotics reduces post-stroke functional outcome of the cases [ 35 – 37 ].…”

Azithromycin Affords Neuroprotection in Rat Undergone Transient Focal Cerebral Ischemia

“…In the present study, assessment of safety outcomes was limited to body temperature, body weight and survival: none of these parameters was affected by treatment with azithromycin. Moreover, in a recent retrospective trial, Smith et al (2019) analyzed data from 2708 patients with ischemic stroke and with an infection, treated with systemic antibiotic therapy, grouped into eight different classes, during the first 2 weeks after stroke onset. The results of this study showed that treatment with macrolides was independently associated with a favorable clinical outcome in any infection or pneumonia complicating stroke (Smith et al, 2019).…”

“…Moreover, in a recent retrospective trial, Smith et al (2019) analyzed data from 2708 patients with ischemic stroke and with an infection, treated with systemic antibiotic therapy, grouped into eight different classes, during the first 2 weeks after stroke onset. The results of this study showed that treatment with macrolides was independently associated with a favorable clinical outcome in any infection or pneumonia complicating stroke (Smith et al, 2019). This was ascribed to the favorable immune-modulatory effects and, eventually, to the neuroprotective properties that macrolides display in preclinical stroke settings.…”

Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

“…Phenotypic descriptions of drug effects will not be discussed either. Comprehensive reviews have aggregated a plethora of data describing the phenotypes of action of polyfunctional antibiotics [36][37][38][39][40][41][42]. The reader is kindly referred to these summaries for further information.…”