Preventive antibacterial treatment improves the general medical and neurological outcome in a mouse model of stroke.
OBJECTIVE
Epidemiological studies have demonstrated a high incidence of infections after severe stroke and their prominent role in morbidity and mortality in stroke patients. In a mouse model, it has been shown recently that stroke is coupled with severe and long-lasting immunosuppression, which is responsible for the development of spontaneous systemic infections. Here, we investigated in the same model the effects of preventive antibiotic treatment on survival and functional outcome of experimental stroke.


METHODS
Mice were subjected to experimental stroke by occlusion of the middle cerebral artery (MCAO) for 60 minutes. A group of mice received moxifloxacin (6x100 mg/kg body weight every 2 hours over 12 hours) either immediately or 12 hours after MCAO. Control animals received the vector only. Behavior, neurological deficit, fever, survival, and body weight were monitored over 14 days. In a subgroup, infarct volume was measured 4 days after MCAO. Microbiological assessment was based on cultures of lung tissue, blood, and feces of animals 3 days after stroke. For a dose-response study, moxifloxacin was given immediately after MCAO in different doses and at different time points.


RESULTS
Microbiological analyses of blood and lung tissue demonstrated high bacterial burden, mainly Escherichia coli, 3 days after stroke. Accordingly, we observed clinical and histological signs of septicemia and pneumonia. Moxifloxacin prevented the development of infections and fever, significantly reduced mortality, and improved neurological outcome.


CONCLUSIONS
Preventive antibiotic treatment may be an important new therapeutical approach to improve outcome in patients with severe stroke.
Meisel
Christian
C
Medical Immunology, Medical Faculty Charité, Humboldt-University, Berlin, Germany.
Prass
Konstantin
K
Braun
Johann
J
Victorov
Ilya
I
Wolf
Tilo
T
Megow
Dirk
D
Halle
Elke
E
Volk
Hans-Dieter
HD
Dirnagl
Ulrich
U
Meisel
Andreas
A
D000818:Animals; D019072:Antibiotic Prophylaxis / Q000379:methods*; D001372:Aza Compounds / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000382:microbiology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control; D005334:Fever / Q000382:microbiology / Q000517:prevention & control; D024841:Fluoroquinolones; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000517:prevention & control*; D007035:Hypothermia / Q000382:microbiology; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000077266:Moxifloxacin; D009894:Opportunistic Infections / Q000382:microbiology / Q000517:prevention & control*; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000517:prevention & control; D011804:Quinolines / Q000627:therapeutic use*; D018805:Sepsis / Q000382:microbiology / Q000517:prevention & control; D020521:Stroke / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D015996:Survival Rate; D016896:Treatment Outcome
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin