Intensive Care National Audit and Research Centre, London, UK.
Health Technol Assess. 2013 Feb;17(3):1-156. doi: 10.3310/hta17030.
There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy.
To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models.
Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis.
Ninety-six UK adult general critical care units.
Consecutive admissions to participating critical care units.
None.
Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species.
Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection.
Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs.
The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis.
Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.
越来越多的证据表明，重症监护病房中非中性粒细胞减少的患者更有可能发生侵袭性真菌感染（IFD）。一些随机对照试验（RCT）评估了非中性粒细胞减少、重症患者的抗真菌预防，结果显示侵袭性 IFD 的风险降低，并提示死亡率降低。有必要建立一种方法，识别和针对那些感染 IFD 风险最高的患者进行抗真菌预防，这些患者最有可能从任何抗真菌预防策略中受益。
开发和验证风险模型，以识别高危侵袭性念珠菌感染的非中性粒细胞减少、重症成年患者，并评估基于这些模型靶向抗真菌预防的成本效益。
系统评价、前瞻性数据收集、统计建模、经济决策建模和信息价值分析。
英国 96 家成人普通重症监护病房。
连续入住参与重症监护病房的患者。
无。
侵袭性真菌感染，定义为血培养或来自正常无菌部位的样本显示微生物或组织病理学报告中的酵母/霉菌细胞。对于统计和经济建模，主要结局是侵袭性念珠菌感染，定义为念珠菌属阳性的 IFD。
系统评价：确定了 13 篇关于重症成年患者 IFD 危险因素、风险模型或临床决策规则的文章。报告与 IFD 显著相关的危险因素被纳入前瞻性数据收集的最终数据集。
2009 年 7 月至 2011 年 3 月期间共收集了 60778 例住院患者的数据。总体而言，383 例患者（0.6%）住院时或住院后发生 IFD。大多数 IFD 患者（94%）为念珠菌属阳性。最常见的感染部位是血液（55%）。单位内 IFD 的发生率为每 1000 例住院患者 4.7 例，单位获得性 IFD 为每 1000 例住院患者 3.2 例。统计建模：在入住重症监护病房时、24 小时和日历年第 3 天结束时建立风险模型。入院时的风险模型具有良好的区分度（c 指数为 0.705）。24 小时时区分度提高（c 指数为 0.823），并在日历年第 3 天结束时保持（c 指数为 0.835）。验证样本中模型性能有所下降。经济决策模型：无论风险阈值如何，与当前实践相比，预防策略的增量质量调整生命年都是积极的，但与增量成本相比则较小。与当前实践相比，每种预防策略的增量净收益均为负值。成本效益接受曲线表明，当前实践是最有可能具有成本效益的策略。在决策模型的所有参数中，结果表明，对整个感兴趣人群进行进一步研究的价值相对于研究成本可能很高。
FIRE 研究的结果来自英国成人普通重症监护病房的高度代表性样本，表明非中性粒细胞减少、重症成年患者 IFD 的发生率较低。IFD 与死亡率显著升高、更密集的器官支持和更长的住院时间相关。风险模型产生了简单的风险模型，可接受地识别出患有侵袭性念珠菌感染“高风险”的患者。经济模型的结果表明，在 NHS 成人普通重症监护病房住院的非中性粒细胞减少、重症成年患者中，预防使用全身性抗真菌药物的最具成本效益的治疗策略是不进行风险评估和不使用抗真菌预防的策略。
本研究由英国国家卫生研究院卫生技术评估计划提供资金。
