藥學專業(yè)畢業(yè)論文外文翻譯--注射用抗生素預防急性中風系統性回顧及薈萃分析（英文）

1、NEUROLOGICAL REVIEWPreventive Antibiotics for Infections in Acute StrokeA Systematic Review and Meta-analysisDiederik van de Beek, MD, PhD; Eelco F. M. Wijdicks, MD, PhD; Frederique H. Vermeij, MD; Rob J. de Haan, PhD; J

2、an M. Prins, MD, PhD; Lodewijk Spanjaard, MD, PhD; Diederik W. J. Dippel, MD, PhD; Paul J. Nederkoorn, MD, PhDObjective: To provide a systematic overview and meta- analysis of randomized clinical trials evaluating preven

3、- tive antibiotics in patients with acute stroke.Data Sources: The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles.Study Selection: Randomized controlled trials on pre- venti

4、ve antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded.Data Extraction: Each study was scored for method- ological key issues and appraised by the Jadad scale. We ex

5、tracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis.Data Synthesis: We identified 4 randomized clinical trials including 426

6、 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tet- racycline or a combination of ?-lactam antibiotic with?-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke

7、onset. Duration of therapy varied be- tween 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infec- tion was sign

8、ificantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for in- fection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 2

9、10 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or tox- icity

10、 was reported.Conclusions: In adults with acute stroke, preventive an- tibiotics reduced the risk of infection, but did not re- duce mortality. The observed effect warrants evaluation of preventive antibiotics in large s

11、troke trials.Arch Neurol. 2009;66(9):1076-1081 INFECTION IS A COMMON COMPLI- cation in the acute phase after stroke and has been described in up to 40% of patients.1 The most common infection after acute stroke is pneumo

12、nia, with reported rates up to 30%. Pneumonia is an early infec- tion; about half of the cases occur within the first 48 hours after stroke onset and almost all within the first week.1 The mor- tality and morbidity assoc

13、iated with pneu- monia is high. In a community-based study including 14 293 patients with stroke,2pneumonia was associated with a relative risk of 3.0 for mortality (95% confidence interval [CI], 2.4-3.7) when adjusted f

14、or admission severity and propensity for pneumonia. In the United States, the an- nual cost of pneumonia as a complica- tion after acute stroke has been esti- mated to be $459 million.3Over the last 3 years, several stud

15、ies have evaluated preventive use of antibi- otics in patients with acute stroke, with conflicting results.1 Current guidelines on acute stroke management state that pre- ventive administration of antibiotics is not indi

16、cated because this treatment has not been proven effective.4 Herein we pro- vide a systematic overview of all random- ized clinical trials evaluating preventive an- tibiotics in patients with acute stroke.METHODSWe selec

17、ted studies on preventive antibiotic treatment in acute stroke. Eligible patients were adults (predefined as aged 16 years or older) with acute stroke, randomized for oral or in- travenous antibiotics of any type or a pl

18、acebo or control group. Each study was scored for methodological key issues, such as inclusion and exclusion criteria, treatment interven-Author Affiliations: Departments of Neurology (Drs van de Beek and Nederkoom), Cli

19、nical Epidemiology and Biostatistics (Dr de Haan), Infectious Diseases (Dr Prins), and Medical Microbiology (Dr Spanjaard), Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Net

20、herlands; Department of Neurology, Division of Critical Care Neurology, Mayo Clinic, Rochester, Minnesota (Dr Wijdicks); and the Department of Neurology (Drs Vermeij and Dippel), Erasmus University Medical Center, Rotter

21、dam, the Netherlands.(REPRINTED) ARCH NEUROL/VOL 66 (NO. 9), SEP 2009 WWW.ARCHNEUROL.COM 1076©2009 American Medical Association. All rights reserved.Downloaded From: http://archneur.jamanetwork.com/ by a University

22、of Amsterdam User on 08/16/2013criteria or inability to complete the treatment protocol. Patients who met eligibility criteria but were excluded after the randomization process were included in the cur- rent analysis. O

23、ne study did not describe withdrawals.10In this trial, patients with a life expectancy of fewer than 90 days were excluded, which resulted in an overall mor- tality rate of 0%.10 One study did not have a blinded out- com

24、e assessment.8 This was also the study that used qua- sirandomization.8The primary outcome measures were the infection rate in the 2 studies and the proportion of patients with fe- ver during admission in 1 study. The de

25、finitions used for infection differed substantially between studies. The cri- teria for infection are presented in Table 2. One study adhered to the official criteria of the US Centers for Dis- ease Control and Preventio

26、n, but used heavily modified criteria.11 Infection rates were not evaluated in all stud- ies. One study focused on the neuroprotective effects of minocycline and did not evaluate infection rates.8 The primary outcome in

27、this trial was the difference be- tween the NIHSS scores of individual patients at the base- line and on day 90. Overall, secondary outcomes were scores on the modified Rankin,6,10 NIHSS,6,8 and Bartel Index.6,9 These se

28、condary outcomes were assessed 90 days after randomization. Case fatality rates were reported in all studies. Sample size calculations were performed in 2 stud- ies.6,9 One study was powered to detect significant effect

29、on the rate of infection based on the assumption of a re- duction from 30% to 15% (OR, 0.41), requiring 480 pa- tients.6 This study was terminated after inclusion of 130 patients because no effect was to be expected with

30、 in- clusion of all 480 patients. At the moment of termina- tion of enrollment, the proportion of patients with in- fection was 17% in placebo group and 18% in the levofloxacin group.6EFFICACY OF ANTIBIOTIC PROPHYLAXISRe

31、sults of the studies are noted in Table 3. The study populations mainly included patients with ischemic stroke(410 of 436 included patients [94%]). One study also in- cluded patients with hemorrhage (deep hematoma, 17; l

32、obar hematoma, 9).6 The overall number of partici- pants with infection was significantly smaller in the an- tibiotic group than in the placebo or control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients) (Table 3)

33、. The number needed to treat to prevent infection was 7. The pooled OR for infection was 0.44 (95% CI, 0.23- 0.86) (Figure). Infections were pneumonia (n=61), uri- nary tract infections (n=21), bronchitis (n=5), and oth-

34、 ers (n=5). The infections that were prevented by antibiotic therapy were those that occurred most frequently, pneu- monia and urinary tract infections. Ten of 210 (4.8%) patients who were treated with an- tibiotics died

35、, compared with 13 of 216 (6.0%) receiv- ing placebo or no treatment (Table 3). The number needed to treat to prevent death was 83. The pooled OR for mor- tality was 0.63 (95% CI, 0.22-1.78) (Figure). Case fatal- ity rat

36、es varied between studies from 0% to 7%. Two stud- ies had positive results on their primary outcome: 1 on improvement of baseline NIHSS score (mean [SD], 1.6[1.9] vs 6.5[3.8]; P ? .001) and 1 on occurrence of fever (P ?

37、 .05).8,10 In 1 study, the result of primary analy- sis was positive for the per protocol analysis only (oc- currence of infections, 6 of 35 [17%] vs 13 of 31 [42%] patients; P=.03).9 In 1 study, the proportion of patien

38、ts with favorable neurological outcome was statistically sig- nificantly reduced and no effect was observed on mor- tality.8 The rate of infection was not evaluated in this study.SAFETY OF ANTIBIOTIC PROPHYLAXISAdverse e

39、vents were described in 3 articles. Antibiotic treatment was not associated with any side effects in 2 studies. The study evaluating mezlocillin plus sulbac- tam described exanthema and elevated liver enzymes each in 1 p

40、atient.10 Antibiotic susceptibility testing of Escher- ichia coli isolates was performed in 1 study.9 No differ- ence was found in antibiotic resistance patterns be- tween bacterial isolates from patients in the moxiflox

41、acin and placebo groups.Table 2. Definitions Used for InfectionSource DefinitionChamorro et al6 Temperature ?37.5°C in 2 determinations; ?37.8°C in a single determination in patients with suggestive symptoms; w

42、hite blood cell count ?11 000/mL or ?4000/mL; pulmonary infiltrate on chest x-rays; or cultures positive for a pathogen Lampl et al8 Not evaluated Harms et al9a Pneumonia, ?1 of: abnormal respiratory examination or pulmo

43、nary infiltrates in chest x-rays, or productive cough with purulent sputum, microbiological cultures from lower respiratory tract or blood cultures, leukocytosis, elevation of CRP; UTI, ?1 of the following: fever (temper

44、ature ?38 · 0°C), urine sample positive for nitrite, leukocyturia, significant bacteriuria Schwarz et al10b Pneumonia, new infiltrate on chest x-ray compatible with the diagnosis of infection plus at least 1 of

45、 the following: fever (temperature ?38.0°C), leukocytosis ?12 000/µL or leukopenia ?3000/µL, purulent tracheal secretions; Tracheobronchitis, purulent tracheal secretions or sputum plus at least 1 of the f

46、ollowing: fever (temperature ?38.0°C), leukocytosis ?12 000/µL or leukopenia ?3000/µL; UTI, ?25 leukocytes/µL in the urine if not explained by other findings; Bacteremia, bacteria in blood cultures; S

47、epsis, clinical evidence of an infection with at least 2 of the following: temperature ?38°C or ?35°C, tachycardia ?90/min, tachypnea ?20/min, leukocytosis ?12 000/µL or leukopenia ?3000/µL; Infection

48、 of unclear origin or other infections, clinical evidence of an infection of unknown origin or any other systemic infectionAbbreviations: CRP, C-reactive protein; UTI, urinary tract infection. aCriteria modified from US

49、Centers for Disease Control and Prevention criteria. bCriteria from Paul Ehrlich Society for chemotherapy.(REPRINTED) ARCH NEUROL/VOL 66 (NO. 9), SEP 2009 WWW.ARCHNEUROL.COM 1078©2009 American Medical Association. A