Risk Factors And Prevention Of Invasive Fungal Infection In Preterm Infants

Objectives:The incidence of invasive fungal infections(IFI) of preterm infants in neonatal intensive care unit(NICU) is increasing year by year. How to early identify high-risk preterm infants susceptible to IFI and effectively prevent IFI become increasingly important. We retrospectively analysed the incidence of IFI and the changing trend of fungi in preterm infants admitted to NICU of Xinhua Hospital in the past four years, determined independent risk factors of IFI in preterm infants and evaluated the efficacy of the comprehensive preventive measures taken by our NICU to prevent IFI in preterm infants. This study aimed to guide clinical early identification of high-risk infants and to find more effective preventive measures for IFI. Methods:1061 preterm infants were included into this study during January 1st, 2010 to December 31 st, 2013, among which 54 preterm infants developed IFI. The first part of the study analysed the incidence of IFI and the changing trend of fungi in preterm infants. The second part of the study was a cohort study including 1061 preterm infants(gestational age <37 weeks). Univariate analysis and logistic regression analysis were used during the process to determine independent risk factors of IFI in preterm infants. The third part of the study was a case-control study including 263 preterm infants whose gestational age(GA) <33 weeks. According to the different type of preventive measures, there were three groups:(1) Control Period(CP): From January 1st, 2010 to June 30 th, 2011. Only basic preventive measures were taken.(2) Fluconazole Prophylaxis Period(FPP): From July 1st, 2011 to November 30 th, 2012. Basic preventive measures and fluconazole prophylaxis were both taken.(3) Comprehensive measure prophylaxis period(CMPP): From December 1st, 2012 to December 31 st, 2013. Basic preventive measures, fluconazole prophylaxis and advanced preventive measures were all taken. We used t test and chi-square test to compare clinical characteristics, risk factors and the incidence of IFI in preterm infants among three groups, to evaluated the efficacy of different preventive measures to prevent IFI in preterm infants Results:The first part of the study:(1) During January 1st, 2010 to December 31 st, 2013, the incidence of IFI was 5.1% in preterm infants. ①The incidence of IFI in preterm infants of different GA: The incidence of IFI in preterm infants of GA<29 weeks was the highest(26.67%), followed by 29 weeks≤GA<31 week(21.11%), 31 weeks≤GA<33 weeks(9.09%), 35 weeks≤GA<37 weeks(1.46%), 33 weeks≤GA<35 weeks(1.17%). ②The incidence of IFI in preterm infants of different birth weight(BW): The incidence of IFI in preterm infants of BW<1000g was the highest(26.67 %), followed by 1000 g ≤ BW < 1500g(23.19 %), 1500 g ≤ BW < 2500g(2.40%), BW≥2500g(0.83%)。③The incidence of IFI in preterm infants of different periods with different type of preventive measures: 6.42% in CP, 6.72% in FPP, 1.33% in CMPP.(2) Pathogens in our NICU during this study period were all Candida species, of which the most common was Candida parapsilosis(22 cases, 40.74%), followed by Candida guilliermondii(18 cases, 33.33%), Candida famate(7 cases, 12.96%), Candida albicans(6 cases, 11.11%), Candida lipolytica(1 cases, 1.85%).(3)The changing trend of fungi: 6 cases(25.00%) of Candida albicans were all in CP, then it disappeared after fluconazole prophylaxis. There were only 3 cases of Candida parapsilosis in CP, while it increased to 19 cases(73.08%) in FPP, and then disappeared after comprehensive preventive measures were taken.The second part of the study: By univariate analysis, GA < 33 weeks, BW<1500g, Apgar score at 1 min≤7, the use of pulmonary surfactant, endotracheal intubation, peripherally inserted central catheter(PICC), stomach tube, total parenteral nutrition(TPN) time>5 days, the use of Tienam or Mepem, the fourth generation cephalosporin, H2 receptor antagonist, maternal preeclampsia and antenatal steroid use were risk factors of IFI in preterm infants. Logistic regression analysis concluded that the independent risk factors of IFI in preterm infants are GA<33 weeks, the use of endotracheal intubation, PICC and H2 receptor antagonist.The third part of the study: During the study period, there were 263 preterm infants whose GA<33 weeks included in this study, among which there were 43 cases developed IFI. The incidence of IFI was 23.16% in CP, 19.00% in FPP and 2.94% in CMPP.(1) There were significant differences between CP and FPP in GA, BW, the length of time using PICC, the use of stomach tube, the fourth generation cephalosporin, H2 receptor antagonist and the combined use of antibiotics. So it was not sure whether fluconazole prophylaxis was effective in preventing IFI of preterm infants in our NICU during this period.(2)There were significant differences between FPP and CMPP in the use of the fourth generation cephalosporin, H2 receptor antagonist and the combined use of antibiotics. There were no significant differences in other clinical characteristics and risk factors between the two groups. The difference was statistically significant between the incidence of IFI in FPP and CMPP. It was proved that the comprehensive preventive measures were effective to prevent IFI in preterm infants. Conclusions:1. During January 1st, 2010 to December 31 st, 2013, the incidence of IFI was 5.1% in preterm infants. The incidence of IFI in preterm infants of GA<29 weeks was the highest(26.67%) in those of different GA. The incidence of IFI in preterm infants of BW<1000g was the highest(26.67%) in those of different BW. The lower the GA, the lower the BW, the higher the incidence of IFI.2. The incidence of IFI in preterm infants of different periods with different type of preventive measures: 6.42% in CP, 6.72% in FPP, 1.33% in CMPP.3. Pathogens were all Candida species, of which the most common was Candida parapsilosis(22 cases, 40.74%). 6 cases(25.00%) of Candida albicans were all in CP, then it disappeared after fluconazole prophylaxis. There were only 3 cases of Candida parapsilosis in CP, while it increased to 19 cases(73.08 %) in FPP, and then disappeared after comprehensive preventive measures were taken.4.The independent risk factors of IFI in preterm infants were GA<33 weeks, the use of endotracheal intubation, PICC and H2 receptor antagonist.5. The comprehensive preventive measures were effective to prevent IFI in preterm infants.