Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials
Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials
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DOI：
10.1093/jac/dki491
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发表时间：
2006-04-01
影响因子：
5.2
通讯作者：
Craig, JC
中科院分区：
文献类型：
--
作者：
Playford, EG;Webster, AC;Craig, JC
目的：本研究旨在系统地识别和总结非中性粒细胞减少的危重患者的抗真菌预防措施对全因死亡率和侵袭性真菌感染发生率的影响。方法：系统回顾和荟萃分析所有语言的随机对照试验，比较非中性粒细胞减少的危重患者中任何抗真菌药物或方案与安慰剂、不使用抗真菌药物或其他抗真菌药物或方案的预防效果。我们检索了Cochrane中央对照试验登记(CENTAL，Cochrane图书馆，2005年第3期)、MEDLINE(1966-2005年9月2日)和EMBASE(1980年-2005年第36周)。我们还手工搜索了参考文献列表、会议记录摘要和科学会议(1998-2004年)，并联系了纳入研究的作者和药物制造商。评估的主要结果是全因死亡率和已证实的侵袭性真菌感染。两名评价者独立应用选择标准，进行质量评估，并采用意向处理方法提取数据。数据采用随机效应模型进行综合，以相对危险度表示，可信区间为95%。结果：共纳入12个独立试验(8个比较氟康唑，4个酮康唑不含抗真菌药物或非吸收药)，涉及1606名随机患者。对于总死亡率和侵袭性真菌感染的结果，几乎所有分别使用氟康唑和酮康唑的试验都显示，预防措施没有显著降低风险。当氟康唑/酮康唑联合使用时，总死亡率降低四分之一(相对危险度0.76，95%可信区间0.59-0.97)，侵袭性真菌感染降低约一半(相对危险度0.46，95%可信区间0.31-0.68)。尽管汇总效果措施的可信区间很宽，但耐唑真菌病原体光滑假丝酵母菌或克鲁斯假丝酵母菌的感染或定植发生率并未显著增加。需要停止治疗的不良反应在接受预防治疗的患者中并不常见。结果尽管临床和方法学特征存在相当大的异质性，但所有试验的结果都是一致的。结论：危重患者应用氟康唑或酮康唑预防侵袭性真菌感染可减少一半，总死亡率减少四分之一。尽管与预防相关的耐唑类念珠菌种类没有显著增加，但试验并不能排除这种影响。在侵袭性真菌感染风险增加的患者中，应考虑使用氟康唑进行抗真菌预防。
Objectives: This study aims to systematically identify and summarize the effects of antifungal prophylaxis in non-neutropenic critically ill adult patients on all-cause mortality and the incidence of invasive fungal infections.Methods: Systematic review and meta-analysis of randomized controlled trials in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal or another antifungal agent or regimen in non-neutropenic critically ill adult patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to 2 September 2005) and EMBASE (1980 to week 36, 2005). We also hand-searched reference lists, abstracts of conference proceedings and scientific meetings (1998-2004) and contacted authors of included studies and pharmaceutical manufacturers. The primary outcomes assessed were all-cause mortality and proven invasive fungal infections. Two reviewers independently applied selection criteria, performed quality assessment and extracted data using an intention-to-treat approach. Data were synthesized using the random effects model and expressed as relative risk with 95% confidence intervals.Results: Twelve unique trials (eight comparing fluconazole and four ketoconazole with no antifungal or a non-absorbable agent) involving 1606 randomized patients were included. For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality by one-quarter (relative risk 0.76, 95% confidence interval 0.59-0.97) and invasive fungal infections by about one-half (relative risk 0.46, 95% confidence interval 0.31-0.68). No significant increase in the incidence of infection or colonization with the azole-resistant fungal pathogens Candida glabrata or Candida krusei was demonstrated, although the confidence intervals of the summary effect measures were wide. Adverse effects requiring treatment discontinuation were not more common amongst patients receiving prophylaxis. Results across all trials were homogeneous despite considerable heterogeneity in clinical and methodological characteristics.Conclusions: Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one-half and total mortality by one-quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.