口服氟康唑在预防早产儿深静脉置管时真菌感染中的临床意义

Clinical significance of oral fluconazole prophylaxis against invasive fungal infection in preterm neonates with peripherally inserted central catheters

目的 探讨口服氟康唑片,在预防出生时胎龄≤32周和（或）出生体重≤1500 g的早产儿深静脉置管（PICC）时侵袭性真菌感染中的临床意义.方法 224例早产儿中未采取预防性使用氟康唑的早产儿（对照组）118例,采用预防性使用氟康唑的早产儿（预防组）106例,回顾性对照分析两组患儿的基本临床特点、侵袭性真菌感染的发生情况以及药物的安全性（谷丙转氨酶、胆红素的变化）.结果两组患儿的基本临床特点进行比较,除经阴道分娩对照组56例（47.5%）,预防组69例（65.1%）,P＜0.005外,其他基本临床特点均无显著差别.将两组患儿引起侵袭性真菌感染的危险因素进行比较,差异均无统计学意义.对照组9例发生侵袭性真菌感染（7.6%）,预防组未发生侵袭性真菌感染（0%）,校正x2值6.56,P＜0.01,差异有统计学意义.预防组于预防性应用氟康唑后2周、4周查肝功能,将谷丙转氨酶及直接胆红素水平与对照组进行比较,2周时谷丙转氨酶异常者对照组10例（8.5%）,预防组12例（11.3%）,P=0.47,直接胆红素异常者对照组8例（6.8%）,预防组9例（8.5%）,P=0.63;4周时谷丙转氨酶异常者对照组4例（3.4%）,预防组6例（5.7%）,P=0.62,直接胆红素异常者对照组4例（3.4%）,预防组9例（8.5%）,P=0.15;差异均无统计学意义.结论 对于出生时胎龄≤32周和（或）出生体重≤1500 g,PICC置管的早产儿,采用口服氟康唑预防侵袭性真菌感染有效,且对于早产儿没有明显的肝细胞毒性,亦不会增加胆汁淤积的发生率.

Objective With the widespread application of peripherally inserted central catheters （PICC） in neonatal intensive care unit （NICU）, the incidence of invasive fungal infections increased significantly than ever. The present study aimed to explore the clinical significance of oral fluconazole in premature infants with gestational age ≤ 32 weeks and/or birth weight ≤ 1500 grams who had catheter insertions. Method This study enrolled 118 infants admitted between January 2006 and December 2007 who did not receive fluconazole prophylaxis （control group） and 106 infants admitted between January 2008 and June 2009 who received oral fluconazole prophylaxis （prophylaxis group）. Statistical analyses were performed by using SPSS 11.5 software. The clinical characteristics and the risk factors for invasive fungal infection between the two groups were compared. Liver functions （ alanine transaminase, ALT and direct bilirubin） were monitored to evaluate the safety of fluconazole prophylaxis. Result Except for the proportion of infants bom via vaginal delivery in the control group （56/118, 47. 5% ） was significantly lower than that in prophylaxis group （69/106, 65.1%, P = 0.007）, there were no significant significant differences in the demographics and other baseline clinical characteristics between the two groups. There were no significant differences in the risk factors for invasive fungal infection between the two groups either.Nine infants developed invasive fungal infection in control group （7. 6% ）, while no invasive fungal infection was found in prophylaxis group （0%, P=0.01 ）. Compared to infants in control group, those in prophylaxis group showed no significant changes in alanine transaminase ALT and direct bilirubin levels at 2 weeks and 4 weeks after fluconazole prophylaxis： the incidences of abnormal ALT and direct bilirubin levels were 8. 5%（10/118） and6.8% （8/118） in control group compared to 11.3% （12/106） and 8.5% （9/106） in prophylaxis group after 2 weeks （ P = 0. 47 and 0. 63 ）; the incidences of abnormal ALT and direct bilirubin levels were 3.4% （4/118） and 3.4% （4/118） in control group compared to 5.7% （6/106） and 8.5%（9/106） in prophylaxis group after 4 weeks （P = 0. 62 and 0. 15）. Conclusion For infants with PICC insertions and gestational ages at birth ≤32 weeks and/or low birth weight ≤ 1500 grams, oral fluconazole is effective to prevent invasive fungal infection. Oral fluconazole in premature infants neither affected the liver function, nor increased the incidence of cholestasis.