Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species
OBJECTIVE. We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates.METHODS. Extremely low birth weight infants 5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000–2001).RESULTS. Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002–2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida -attributable deaths occurred during 2002–2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002–2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis.CONCLUSION. During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.
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机译：目的。我们评估了氟康唑对极低出生体重婴儿的预防措施对侵袭性念珠菌病发病率，侵袭性念珠菌病相关死亡率以及念珠菌分离株对氟康唑的敏感性的影响。小于5天的极低出生体重婴儿（具有肝功能障碍的婴儿除外）符合氟康唑预防的条件。将2002年4月至2006年3月间侵袭性念珠菌病的NICU婴儿（所有出生体重）与氟康唑预防之前（2000-2001年）侵袭性念珠菌病的婴儿进行比较。结果。 22例氟康唑预防期间有侵袭性念珠菌病（所有念珠菌血症）;氟康唑预防前有19例（念珠菌血症：17例;脑膜炎：2例）。在2002–2006年，NICU婴儿的侵袭性念珠菌病发病率从预防氟康唑之前的0.6％（3012婴儿中的19例）下降到0.3％（6393婴儿中的22％），而极低出生体重的婴儿则下降了3.6倍。预防氟康唑期间，2002年至2006年期间未发生因念珠菌引起的死亡，相比之下，预防氟康唑之前有4例（21％）死亡。侵袭性念珠菌病的发病在2002-2006年晚些时候（23.5 vs 12天），但是危险因素相似。侵入性念珠菌病物种分布保持稳定。在409名接受氟康唑预防的婴儿中，有119名（29％）接受了42天的治疗。氟康唑的预防时间更短与242例（59％）不再需要静脉注射，与非侵入性念珠菌病相关的死亡29例（7％），医院转移8例（2％），侵入性念珠菌病诊断8例（2％）有关），而血清转氨酶水平的短暂升高为4（1％）。接受氟康唑预防的一百二十七名婴儿（31％）在住院期间发生了胆汁淤积，其中三分之二患有其他易感疾病。在多因素logistic回归分析中，坏死性小肠结肠炎和总肠胃外营养日数的增加，但氟康唑日剂量的增加并未增加，与胆汁淤积的发生密切相关。在预防氟康唑的4年中，极低出生体重婴儿的侵袭性念珠菌病发病率和侵袭性念珠菌病相关死亡率显着降低，而未出现耐氟康唑的念珠菌物种。
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