Preventive Antibiotics for Infections in Acute Stroke

Beek, Diederik van de; Wijdicks, Eelco F. M.; Vermeij, Frédérique H; Haan, Rob J. de; Prins, Jan M.; Spanjaard, Lodewijk; Dippel, Diederik W.J.; Nederkoorn, Paul J.

doi:10.1001/archneurol.2009.176

Cited by 86 publications

(71 citation statements)

References 22 publications

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“…18 Similarly, preventively treated mice were also protected from infections in our study. However, treatment with antibiotics improved survival significantly, independent of whether it was given preventively or immediately after diagnosis of pneumonia.…”

Section: Discussionsupporting

confidence: 75%

“…[15][16][17] A metanalysis on these trials suggests that PAT reduces the occurrence of poststroke infections, but remains ineffective in terms of outcome. 18 Consequently, the current 'gold standard' by stroke guidelines is treatment immediately after diagnosis of infections. Two main reasons might account for the discrepancy between experimental and clinical findings.…”

Section: Introductionmentioning

confidence: 99%

“…First, clinical trials were not powered to address treatment effects on neurologic outcome. 18,19 Second, our experimental model might not be predictive for the clinical setting. In fact, we tested PAT against 'placebo' in our experimental model 14 but not against the above-mentioned standard treatment, which is obviously not reflecting clinical practice properly.…”

Section: Introductionmentioning

confidence: 99%

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Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

Hetze

Engel

Römer

et al. 2013

J Cereb Blood Flow Metab

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Stroke patients are prone to life-threatening bacterial pneumonia. Previous experimental stroke studies have demonstrated that preventive antibiotic treatment (PAT) improves outcome compared with placebo treatment, which however does not model the clinical setting properly. Here we investigate whether PAT is superior to the current clinical 'gold standard' for treating poststroke infections. Therefore, we modeled stroke care according to the current stroke guidelines recommending early antibiotic treatment after diagnosing infections. To reliably diagnose pneumonia in living mice, we established a general health score and a magnetic resonance imaging protocol for radiologic confirmation. Compared with standard treatment after diagnosis by these methods, PAT not only abolished pneumonia successfully but also improved general medical outcome. Both, preventive and standard antibiotic treatment using enrofloxacin improved survival in a similar way compared with placebo treatment. However, in contrast to standard treatment, only PAT improved functional outcome assessed by gait analysis. In conclusion, standard and preventive treatment approach reduced poststroke mortality, however at the cost of a worse neurologic outcome compared with preventive approach. These data support the concept of PAT for treating patients at risk for poststroke infections and warrant phase III trials to prove this concept in clinical setting.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

Hetze

Engel

Römer

et al. 2013

J Cereb Blood Flow Metab

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“…43 This might be attributable to inclusion of patients with low risk of developing SAP in these studies. The AIS-APS and other SAP predictive tools could be used to identify patients who are at high risk of developing SAP after stroke.…”

Section: May 2013mentioning

confidence: 99%

Novel Risk Score to Predict Pneumonia After Acute Ischemic Stroke

Shen²,

Pan

et al. 2013

Stroke

142

157

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Background and Purpose— To develop and validate a risk score (acute ischemic stroke-associated pneumonia score [AIS-APS]) for predicting in-hospital stroke-associated pneumonia (SAP) after AIS. Methods— The AIS-APS was developed based on the China National Stroke Registry, in which eligible patients were randomly classified into derivation (60%) and internal validation cohort (40%). External validation was performed using the prospective Chinese Intracranial Atherosclerosis Study. Independent predictors of in-hospital SAP after AIS were obtained using multivariable logistic regression, and β-coefficients were used to generate point scoring system of the AIS-APS. The area under the receiver operating characteristic curve and the Hosmer–Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. Results— The overall in-hospital SAP after AIS was 11.4%, 11.3%, and 7.3% in the derivation (n=8820), internal (n=5882) and external (n=3037) validation cohort, respectively. A 34-point AIS-APS was developed from the set of independent predictors including age, history of atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease and current smoking, prestroke dependence, dysphagia, admission National Institutes of Health Stroke Scale score, Glasgow Coma Scale score, stroke subtype (Oxfordshire), and blood glucose. The AIS-APS showed good discrimination (area under the receiver operating characteristic curve) in the internal (0.785; 95% confidence interval, 0.766–0.803) and external (0.792; 95% confidence interval, 0.761–0.823) validation cohort. The AIS-APS was well calibrated (Hosmer–Lemeshow test) in the internal ( P =0.22) and external ( P =0.30) validation cohort. When compared with 3 prior scores, the AIS-APS showed significantly better discrimination with regard to in-hospital SAP after AIS (all P <0.0001). Conclusions— The AIS-APS is a valid risk score for predicting in-hospital SAP after AIS.

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“…Therefore, comparability of these studies is severely limited. Nonetheless, 3 metaanalyses of the studies (published until 2008), written by the same group of authors, and predictably reaching comparable results, have already been published [52][53][54]. Not surprisingly, one of the authors' main conclusions was that the studies were heterogeneous [54].…”

Section: Clinical Studies On Preventive Antibiotic Therapy After Strokementioning

confidence: 99%

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Schwarz

2016

Neurotherapeutics

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Infections, in particular pneumonia, are common complications in patients with acute stroke and are associated with a less favorable neurologic and functional outcome. Patients with severe stroke and dysphagia are at highest risk of infection. Experimental and clinical data suggest stroke-induced immunodeficiency as a major factor contributing to the high incidence of infection after stroke. Preclinical studies support the potential benefit of preventive antibiotic therapy in acute stroke for lowering the incidence of infection and improving clinical outcome. Several smaller clinical trials on preventive antibiotic therapy in patients with stroke conducted during the last 10 years yielded inconclusive results. Recently, 2 large, open-label, controlled trials failed to demonstrate an improved clinical outcome after preventive antibiotic therapy in patients with acute stroke treated in specialized stroke units. In the BPreventive Antibiotics in Stroke Study^, antibiotic therapy lowered the rate of infection but did not influence outcome. In the STROKE-INF study, performed in patients with dysphagia after stroke, antibiotic therapy did not lower the incidence of pneumonia and had no prognostic significance. At present, preventive antibiotic therapy cannot be recommended as a therapeutic option for acute stroke.

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Preventive Antibiotics for Infections in Acute Stroke

Cited by 86 publications

References 22 publications

Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

Novel Risk Score to Predict Pneumonia After Acute Ischemic Stroke

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

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