制霉菌素预防重症监护病房机械通气患者侵袭性真菌感染的临床研究

The clinical research of nystatin in prevention of invasive fungal infectious in patients on mechanical ventilation in intensive care unit

目的 观察经胃肠道给予制霉菌素对重症监护病房（ICU）机械通气患者侵袭性真菌感染（IFI）发生率及预后的影响.方法 采用前瞻性观察性研究,选择2012年5月1日至2013年4月30日江西省人民医院重症医学科需行有创机械通气的危重症患者,按信封法随机分配至两组,干预组经胃管内注入制霉菌素1000 kU每日3次,对照组给予促进胃肠动力药物作为安慰剂.入组后每隔3d（T0、T3、T6、T9）留取标本,观察分离菌株的分布情况,并计算校正定植指数（CCI）,统计念珠菌血症发生率及28 d病死率,记录患者ICU住院时间和总住院时间.结果 共有124例患者入选,共分离出874株菌株,以白色念珠菌居多,占57.6％（503/874）,最常见的定植部位为口咽部,占35.6％（311/874）.干预组T6、T9时CCI明显低于对照组[T6∶0.19±0.10比0.39±0.15,T9∶0.00（0.10）比0.45（0.30）,均P＜ 0.05]；干预组念珠菌血症发生率较对照组有所降低[5.0％（3/60）比7.8％（5/64）,P＞0.05],28 d病死率明显低于对照组[18.3％（11/60）比34.4％（22/64）,P＜ 0.05].干预组ICU住院时间明显短于对照组（d∶9.56±3.47比11.89±6.32,P＜0.05）,但总住院时间（d∶18.35±7.42比20.58±8.77）无明显统计学差异（P＞0.05）.结论 经胃肠道给予制霉菌素片能减少ICU危重症患者白色念珠菌定植发生,缩短患者ICU住院时间.

Objective To observe the effect of nystatin on incidence of invasive fungal infections （IFI） and the prognosis of mechanically ventilated critically ill patients.Methods A prospective study was conducted.Critical ill patients admitted to Department of Critical Care Medicine of Jiangxi Provincial People＇s Hospital from May I st,2012 to April 30th,2013 needing mechanical ventilation were enrolled.The patients were randomly divided into two groups by envelope method.Patients in the nystatin group were administered nystatin 1000 kU three times a day via the gastric tube; and patients in the control group were given gastrointestinal prokinetic drug as placebo.The specimens were collected every 3 days throughout the ICU stay （T0,T3,T6,T9）,the strain distribution was observed,and the corrected colonization index （CCI） of all patients were calculated.The incidence of candidemia and 28-day mortality as well as the duration of stay in ICU and hospital were also recorded.Results A total of 874 strains were isolated from 124 patients,of which Candida albicans accounted for 57.6％ （503/874）.The most frequently colonized body sites were oropharyngeal site,account for 35.6％ （311/874）.The CCI of the nystatin group were lower than those of the control group at T6 and T9 [T6∶0.19 ± 0.10 vs.0.39 ± 0.15,T9∶0.00 （0.10） vs.0.45 （0.30）,all P＜0.05].The incidence of candidemia in the nystatin group was slightly lower than that in control group [0.5％ （3/60） vs.7.8％ （5/64）,P＞0.05].The mortality in the nvstatin group was lower than that in control group [18.3％ （11/60） vs.34.4％ （22/64）,P＜0.05].ICU day in the nystatin group was shorter than that in the control group （days ∶ 9.56 ± 3.47 vs.11.89 ± 6.32,P＜0.05）.However,hospital day was similar in the two groups （days∶18.35 ±7.42 vs.20.58 ±8.77,P＞0.05）.Conclusion Nystatin might reduce the colonization of Candida albicans and was associated with shorter ICU day.