Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.
BACKGROUND
Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.


METHODS
Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.


RESULTS
On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.


CONCLUSIONS
PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.


BACKGROUND
Controlled-Trials.com ISRCTN74386719.
Harms
Hendrik
H
Department of Neurology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
Prass
Konstantin
K
Meisel
Christian
C
Klehmet
Juliane
J
Rogge
Witold
W
Drenckhahn
Christoph
C
Göhler
Jos
J
Bereswill
Stefan
S
Göbel
Ulf
U
Wernecke
Klaus Dieter
KD
Wolf
Tilo
T
Arnold
Guy
G
Halle
Elke
E
Volk
Hans-Dieter
HD
Dirnagl
Ulrich
U
Meisel
Andreas
A
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001372:Aza Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001424:Bacterial Infections / Q000150:complications / Q000517:prevention & control*; D001831:Body Temperature; D002545:Brain Ischemia / Q000150:complications*; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D000077266:Moxifloxacin; D010919:Placebos; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects; D012121:Respiration, Artificial; D012307:Risk Factors; D020521:Stroke / Q000150:complications*; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D010919:Placebos; D011804:Quinolines; D002097:C-Reactive Protein; D000077266:Moxifloxacin