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(Stroke. 2005;36:1495.)
© 2005 American Heart Association, Inc.

Original Contributions

The Early Systemic Prophylaxis of Infection After Stroke Study

A Randomized Clinical Trial

A. Chamorro, MD; J.P. Horcajada, MD; V. Obach, MD; M. Vargas, PhD; M. Revilla, MD; F. Torres, MD; A. Cervera, MD; A.M. Planas, PhD J. Mensa, MD

From the Stroke Unit, Hospital Clínic and Institut d’ Investigacions Biomédiques August Pi i Sunyer (IDIBAPS; A.C., V.O., M.R.), Barcelona, Spain; the Infectious Diseases Unit (J.P.H., M.V., J.M.), Hospital Clínic, Barcelona, Spain; the Pharmacology and Toxicology Department, Consejo Superior de Investigaciones Científicas (IIBB-CSIC) and IDIBAPS (A.M.P.), Barcelona, Spain; and the Clinical Pharmacology Unit-Unitat d’Avaluació I Suport de Projectes (UASP; F.T.), Hospital Clínic, Barcelona, Spain.

Correspondence to Ángel Chamorro, MD, PhD, Stroke Unit, Hospital Clínic, Villarroel 170. 08036-Barcelona, Spain. E-mail achamorro{at}ub.edu

	Abstract

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Background and Purpose— Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored.

Objective and

Methods— The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9% physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15% absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90.

Results— Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83) at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30% and 33% (P=0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03).

Conclusions— Prophylactic administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.

Key Words: randomized controlled trials • stroke

	Introduction

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Infections are diagnosed in 21% to 65% of patients with stroke,^1–6 and this complication may increase the mortality and worsen clinical outcome.^2,7–9 Acute infections may also increase the risk of stroke,¹⁰ particularly during the first 3 days of infection.¹¹ The mechanisms responsible for worse outcome after infection are compound, including the effects of hypoxia, homeostasis unbalance, and fever.¹² However, the administration of antipyretics to febrile or afebrile patients with acute stroke did not show a robust clinical impact,^13–14 calling for alternative or additional methods to achieve effective thermoregulation in stroke.

Current guidelines do not recommend empirical antibiotic prophylaxis in patients with acute stroke but encourage a search of infections to start tailored treatment without delay.^15,16 However, these recommendations are not supported by randomized controlled trials.¹⁷ The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) Study was designed to address whether early antibiotic prophylaxis in afebrile patients with acute stroke reduced the incidence of infections and improved the clinical outcome.

Recently, it has been reported in mice an increased infectious vulnerability secondary to a stroke-induced immunodepression syndrome.¹⁸ Several preclinical studies have described the neuroprotective effects of moxifloxacin¹⁹ and minocycline²⁰ after transient focal brain ischemia, further justifying a clinical trial such ESPIAS.

	Materials and Methods

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ESPIAS is an academic, randomized, double-blind administration of an antibiotic or placebo within 24 hours from symptom onset in patients with ischemic or hemorrhagic stroke. The study was performed between March 2002 and March 2004 and had official approval by our institutional review board. Serious adverse events were reported to an independent data and safety monitoring board. Eligibility criteria included age older than 18 years, baseline National Institutes of Health Stroke Scale (NIHSS) 5, and written informed consent from the patients or their next-of-kin. Exclusion criteria were infection on admission or within the preceding 3 months, axillary temperature >37. 7°C, allergy to fluoroquinolones, history of epilepsy, seizures at stroke onset, serum creatinine >2.5 mg/dL, and use of antibiotics, immunosuppressants, or steroids within the preceding 3 months.

Patients were admitted into the stroke unit and managed by stroke neurologists and specialists on infectious diseases. A flow diagram showing the progress of patients throughout the trial is shown in Figure 1. Patients had a brain CT scan or brain MRI before treatment onset. The diagnostic work-up was conducted as appropriate to identify the cause of stroke. Hemorrhagic strokes were classified as lobar or deep hematomas, and ischemic strokes were categorized as cardioembolic, lacunar, atherothrombotic, or caused by unknown factors.²¹ Neurological function was assessed every 8 hours and clinical worsening defined an increase of at least 4 points in the NIHSS score.²² Oxygenation, heart rate, blood pressure, and respiratory function were continuously monitored during the first 3 days, and axillary temperature was recorded every 4 hours until hospital discharge. At 3 months, stroke survivors were assessed using the NIHSS, the modified Rankin Scale, and the Barthel Index. Favorable outcome defined a modified Rankin Scale <2, NIHSS score <2, and a Barthel Index of 95 or 100.

View larger version (22K): [in this window] [in a new window]   Figure 1. Flow diagram of the trial.

Patients were randomly allocated to receive for 3 days 500 mg/100 mL levofloxacin or an identical volume of placebo (0.9% physiological serum) intravenously, using a computer-generated number sheet, and opening a numbered sealed envelope by a pharmacist, nurse, or fellow. Levofloxacin was selected for its excellent in vitro activity and clinical efficacy against organisms associated with upper and lower respiratory tract infections and common urinary tract pathogens that may complicate stroke.²³ Available postmarketing surveillance data also indicated that levofloxacin possessed an unparalleled safety database.²⁴ Study treatment was prepared at the central pharmacy of the institution and kept within its premises until allocation.

Blood samples were collected before treatment onset and at days 1, 2, 3, 4, 7, and 90 to assess white blood cell count (Pentra DX 120; ABX Diagnostics) and C-reactive protein (Dade-Behring, Newark, NJ) levels. Specialists on infectious diseases established the occurrence of incident infections and advised the most appropriate management. Blood cultures were obtained if temperature >37.5°C. Urine or respiratory samples were assessed in the presence of appropriate symptoms or if fever was not accompanied by any focal symptoms.

Infection was defined if temperature >37.5°C in 2 determinations or >37.8°C in a single determination in patients with suggestive symptoms (ie, cough, dyspnea, pleuritic pain, urinary tract symptoms), white blood cell count >11 000/mL or <4000/mL, pulmonary infiltrate on chest x-rays, or cultures positive for a pathogen. Otherwise, temperature >37.8°C was classified as noninfectious hyperthermia. Infection was further classified as early, if it occurred within the first 7 days after stroke, and late, when it supervened between days 8 and 90 after stroke. The study medication was withdrawn when an incident infection was diagnosed. In these instances, an antibiotic regime was initiated as appropriate, preferentially with levofloxacin, unless an antibiogram recommended otherwise.

The primary outcome measure of ESPIAS was the difference in early infection between treatment groups. Secondary outcome measures were mortality and favorable outcome at day 90, which indicated a modified Rankin Scale <2, a NIHSS score <2, and a Barthel Index of 95 or 100.

Statistical Analysis
To ensure 80% power for the primary efficacy on intention to treat analysis, 240 patients were required, assuming a rate of infection in the placebo group of 30% and a 15% absolute risk reduction by levofloxacin. A blinded interim analysis was planned by the data and safety monitoring board at 50% of the information fraction based on -spending function resembling the O’Brien-Fleming type (East v3.3.0 program). Dichotomous and categorical data were compared by use of Fisher exact test. Continuous variables were assessed with Student t test for normally distributed data or the Mann-Whitney U test otherwise. All tests were 2-tailed and at a 0.05 level of significance. ANCOVA adjusted for baseline values was used to assess changes of C-reactive protein, white blood cell counts, and temperature; between-treatment comparisons were only performed when the interaction term of time with either infection or treatment was statistically significant. Logistic regression modeling was used to assess baseline predictors of favorable outcome at day 90. The analysis was executed using SAS v8.2.

Role of the Funding Source
The Fondo of Investigaciones Sanitarias of the Spanish Ministry of Health (grant FIS 02-0477) funded ESPIAS.

	Results

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Premature Termination of the Study
The data and safety monitoring board recommended the premature stop of the trial after the analysis of the first 130 patients. At that point, the main end point incidence was 17.2% for placebo (11/64) and 18.2% for levofloxacin (12/66), and the innermost ascending pointed line was crossed by the calculated Z statistic, leading to the conclusion that the working hypothesis was not plausible.

Study Population
Although there were no new inclusions, 6 patients completed the follow-up (3 in levofloxacin and 3 in the placebo arm) after that sequential analysis. The final intention-to-treat population was then formed by 136 patients: 67 patients allocated levofloxacin, and 69 allocated placebo. As shown in Figure 1, treatment was interrupted prematurely before the 3 days in similar proportions in the 2 treatment groups (P=0.95). None was lost to follow-up or premature interruptions as the result of adverse events.

More patients had coronary heart disease or deep hematoma in the levofloxacin group, but the differences did not reach statistical significance, as shown in Table 1. Other baseline characteristics, including the severity of stroke, vital functions, biochemistry, or treatment delay, were similar in the 2 treatment groups, as described in Table 1.

View this table: [in this window] [in a new window]   TABLE 1. Main Characteristics of the Study Population

Primary Outcome Measure
Twenty-four patients (17.6%) had early infection, and 19 patients (13.9%) had late infection. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83) at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30% and 33% (P=0.70) at day 90. Mean (SD) time delay to infection was similar in levofloxacin and placebo groups (3.4 [4.2] versus 3.7 [3.5] days; P=0.82). Early infections included 18 (75%) respiratory tract infections, 5 (21%) urinary tract infections , and 1 (4%) catheter-related phlebitis. Late infections included 9 (47%) respiratory tract infections and 10 (53%) urinary tract infections.

With the exception of a higher prevalence of chronic obstructive pulmonary disease, patients with an early infection disclosed no significant differences in demographics, baseline vital functions, and risk factors compared with noninfected patients, as indicated in Table 2. However, patients with infection had more severe strokes on admission, higher white blood cell counts greater mortality, and worse neurological outcome. At follow-up, white blood cell counts, C-reactive protein, and temperature increased more significantly in patients with early infection, regardless of treatment allocation, as shown in Figure 2.

View this table: [in this window] [in a new window]   TABLE 2. Characteristics and Outcome Measures of Patients With and Without Early Infection

View larger version (23K): [in this window] [in a new window]   Figure 2. Longitudinal changes of C-reactive protein, total leukocyte count, and axillary temperature in relation to incident infection (a,c,e) and treatment allocation (b,d,f).

Secondary Outcome Measures
Favorable outcome at day 90 was inversely and independently associated with baseline NIHSS score (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03) after adjustment for the effect of age, treatment delay, early infection, stroke subtype, temperature, and white blood cell count.^25–29 An exploratory analysis restricted to patients with ischemic stroke confirmed the independent negative predictor value of baseline NIHSS (OR, 0.66; 95% CI, 0.51 to 0.86; P=0.003) and allocation to levofloxacin (OR, 0.17; 95% CI, 0.02 to 0.99; P=0.04).

Mortality at day 90 was nonsignificantly increased in patients allocated to levofloxacin (24% versus 13%; P=0.12). The proportion of deaths primarily caused by an infectious complication was 19% in the levofloxacin group and 22% in the placebo group (P=0.21).

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Observational studies have described a worse outcome in patients with infection early after stroke,^2,7–9 but current acute stroke therapy guidelines dissuade,¹⁵ or disregard,¹⁶ the value of antibiotic prophylaxis. ESPIAS is the first randomized, double blind, placebo-controlled study of early antibiotic prophylaxis in nonseptic acute stroke. The study was interrupted prematurely because a pre-established futility analysis showed that the primary clinical hypothesis could not be rejected for the rate of infection was similar in patients allocated to levofloxacin or placebo. Allocation to placebo disclosed an infection rate lower than predicted, most likely because the study was performed in a stroke unit rather than in a conventional ward.²⁵ However, this lower event rate did not decrease the statistical power to identify percent differences in treatment response. Nevertheless, the study was probably not properly powered to investigate the safety of levofloxacin.

ESPIAS found that levofloxacin significantly reduced the chances of stroke recovery despite the adjustment of other putative outcome predictors.^25–29 More patients with deep hematoma had been randomly allocated to levofloxacin, but we confirmed the deleterious effects of levofloxacin in exploratory analyses restricted to patients with ischemic stroke. Levofloxacin had previously shown a very low incidence of side effects from the central nervous system, including headache, anxiety, sleeplessness, agitation, or seizures.²⁴ However, the safety of levofloxacin had never been explored specifically in stroke patients, and it could be argued that in this clinical setting the drug could be detrimental because of its inhibitory effects on GABA neurotransmission and/or its excitatory effects on glutamate.^30–31 Nevertheless, a note of caution is required because clinical outcome was a secondary aim of the study, and the confidence intervals of the effect of levofloxacin did not exclude that its deleterious contribution might be small.

In agreement with previous studies,³² half of the infections occurred within the first week after stroke, more frequently in patients with severe stroke on admission.^1–6 The incidence of late infections was similar in the 2 treatment groups, denying that levofloxacin delayed the appearance of infection. The patients with an infection that developed early after stroke had an increased mortality and greater neurological impairment at day 90, although the negative prognostic effect of early infection was mostly explained by the greater severity of the stroke before the infection.

In summary, ESPIAS showed that in patients managed in a stroke unit, levofloxacin did not prevent infections more effectively than placebo, emphasizing the importance of general measures for infection prophylaxis. Some evidence also suggested that levofloxacin could lessen the chances of functional recovery. Contrarily, ESPIAS did not exclude that other levofloxacin dose regimens or alternative antibiotics might differ from these findings. Yet stroke patients at special risk for infection or managed in less specialized hospital settings might obtain some benefits from a prophylactic treatment. Meanwhile, admission into a stroke unit and early detection and treatment of infections seem the most judicious recommendations. Whether levofloxacin can be safely given to acute stroke patients with ongoing infection deserves additional study.

Received March 10, 2005; revision received April 11, 2005; accepted April 27, 2005.

	References

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1. Johnston KC, Li JY, Lyden PD, Hanson SK, Feasby TE, Adams RJ, Faught RE Jr, Haley EC Jr; for the RANTTAS Investigators. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. Stroke. 1998; 29: 447–453.[Abstract/Free Full Text]
2. Grau AJ, Buggle F, Schnitzler P, Spiel M, Lichy C, Hacke W. Fever and infection early after ischemic stroke. J Neurol Sci. 1999; 171: 115–120.[CrossRef][Medline] [Order article via Infotrieve]
3. Langhorne P, Stott DJ, Robertson L, MacDonald J, Jones L, McAlpine C, Dick F, Taylor GS, Murray G. Medical complications after stroke: a multicenter study. Stroke. 2000; 31: 1223–1229.[Abstract/Free Full Text]
4. Weimar C, Roth MP, Zillessen G, Glahn J, Wimmer ML, Busse O, Haberl RL, Diener HC; for the German Stroke Date Bank Collaborators. Complications following acute ischemic stroke. Eur Neurol. 2002; 48: 133–140.[Medline] [Order article via Infotrieve]
5. Davenport RJ, Dennis MS, Wellwood I, Warlow CP. Complications after acute stroke. Stroke. 1996; 27: 415–420.[Abstract/Free Full Text]
6. Castillo J, Dávalos A, Marrugat J, Noya M. Timing for fever-related brain damage in acute ischemic stroke. Stroke. 1998; 29: 2455–2460.[Abstract/Free Full Text]
7. Hindfeldt B. The prognostic significance of subfebrility and fever in ischemic cerebral infarction. Acta Neurol Scand. 1976; 53: 72–79.[Medline] [Order article via Infotrieve]
8. Azzimondi G, Bassein L, Nonino F, Fiorani L, Vignatelli L, Re G, D’Alessandro R. Fever in acute stroke worsens prognosis. A prospective study. Stroke. 1995; 26: 2040–2043.[Abstract/Free Full Text]
9. Nakagawa T, Sekizawa K, Arai H, Kikuchi R, Manabe K, Sasaki H. High incidence of pneumonia in elderly patients with basal ganglia infarction. Arch Intern Med. 1997; 157: 321–324.[Abstract]
10. Lindsberg PJ, Grau AJ. Inflammation and infection as risk factors for ischemic stroke. Stroke. 2003; 34: 2518–2532.[Abstract/Free Full Text]
11. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004; 351: 2611–2618.[Abstract/Free Full Text]
12. Ginsberg MD, Busto R. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke. 1998; 29: 529–534.[Abstract/Free Full Text]
13. Kasner SE, Wein T, Piriyawat P, Villar-Cordova CE, Chalela JA, Krieger DW, Morgenstern LB, Kimmel SE, Grotta JC. Acetaminophen for altering body temperature in acute stroke. A randomized clinical trial. Stroke. 2002; 33: 130.[Abstract/Free Full Text]
14. Koennecke HC, Leistner S. Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study. Neurology. 2001; 26: 57:2301–2303.
15. The European Stroke Initiative Executive Committee and the EUSI Writing Committee European Stroke Initiative Recommendations for Stroke Management—Update 2003. Cerebrovasc Dis. 2003; 16: 311–337.[CrossRef][Medline] [Order article via Infotrieve]
16. Adams HP Jr., Adams RJ, Brott T, del Zoppo GJ, Furlan A, Goldstein LB, Grubb RL, Higashida R, Kidwell C, Kwiatkowski TG, Marler JR, Hademenos GJ; for the Stroke Council of the Am Stroke Association. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the Am Stroke Association. Stroke. 2003; 34: 1056–1083.[Free Full Text]
17. Warlow C, Sudlow C, Dennis M, Wardlaw J, Sandercock P. Stroke. Lancet. 2003; 362: 1211–1214.[CrossRef][Medline] [Order article via Infotrieve]
18. Prass K, Meisel C, Höflich C, Victorov I, Wolf T, Megow D, Halle E, Volk HD, Dirnagl U, Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation: reversal by post-stroke Th1-like immunostimulation. J Exp Med. 2003; 198: 725–736.[Abstract/Free Full Text]
19. Meisel C, Prass K, Braun J, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A. Preventive antibacterial treatment improves the general medical and neurological outcome in a mouse model of stroke. Stroke. 2004; 35: 2–6.[Abstract/Free Full Text]
20. Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, Hill WD, Feuerstein G, Hess DC. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurology. 2004; 4: 7.[Medline] [Order article via Infotrieve]
21. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute stroke. Definitions for use in a multicenter clinical trial. Stroke. 1993; 24: 35–41.[Abstract/Free Full Text]
22. Linfante I, Llinas RH, Selim M, Chaves C, Kumar S, Parker RA, Caplan LR, Schlaug G. Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke. 2002; 33: 2066–2071.[Abstract/Free Full Text]
23. Wimer SM, Garrison MW. Levofloxacin: a therapeutic review. Clin Ther. 1998; 20: 1049–1070.[CrossRef][Medline] [Order article via Infotrieve]
24. Carbon C. Comparison of side effects of levofloxacin versus other fluoroquinolones. Chemotherapy. 2001; 47: 9–14.[Medline] [Order article via Infotrieve]
25. Jongbloed L. Prediction of function after stroke: a critical review. Stroke. 1986; 17: 765–776.[Abstract/Free Full Text]
26. German Stroke Study Collaboration. Predicting outcome after acute ischemic stroke. An external validation of prognostic models. Neurology. 2004; 62: 581–585.[Abstract/Free Full Text]
27. Audebert HJ, Rott MM, Eck T, Haberl RL. Systemic Inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis. Stroke. 2004; 35: 2128–2133.[Abstract/Free Full Text]
28. Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke. 1999; 30: 981–985.[Abstract/Free Full Text]
29. Stroke Unit Trialists’ Collaboration. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. BMJ. 1997; 314: 1151–1159.[Abstract/Free Full Text]
30. Schmuck G, Schurmann A, Schluter G Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Antimicrob Agents Chemother. 1998; 42: 1831–1836.[Abstract/Free Full Text]
31. Dodd PR, Davies LP, Watson WE, Nielsen B, Dyer JA, Wong LS, Johnston GA. Neurochemical studies on quinolone antibiotics: effects on glutamate, GABA and adenosine systems in mammalian CNS. Pharmacol Toxicol. 1989; 64: 404–411.[Medline] [Order article via Infotrieve]
32. Kalra L, Yu G, Wilson K, Roots P. Medical complications during stroke rehabilitation. Stroke. 1995; 26: 990–994.[Abstract/Free Full Text]

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