Leonart Letícia Paula, Tonin Fernanda Stumpf, Ferreira Vinicius Lins, Tavares da Silva Penteado Suelem, de Araújo Motta Fábio, Pontarolo Roberto
Department of Pharmacy, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Pelé Pequeno Príncipe Research Institute, Pequeno Príncipe Hospital, Curitiba, PR, Brazil.
J Pediatr. 2017 Jun;185:129-135.e6. doi: 10.1016/j.jpeds.2017.02.039. Epub 2017 Mar 10.
To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates.
A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted.
Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different.
Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.
评估不同剂量氟康唑用于新生儿侵袭性真菌感染预防性治疗的安全性和有效性。
通过PubMed、Scopus和Web of Science进行系统检索，并进行了手工检索。本综述纳入了仅在新生儿重症监护病房（NICU）接受氟康唑预防性治疗侵袭性真菌感染的新生儿的随机对照试验，无论剂量或治疗方案如何。提取了基线特征、确诊侵袭性念珠菌感染的发生率、总死亡率以及侵袭性念珠菌感染相关死亡率的数据。
本综述纳入了11项研究，氟康唑剂量为3、4或6mg/kg。当将侵袭性念珠菌感染发生率和侵袭性念珠菌感染相关死亡率作为观察指标时，发现3mg/kg和6mg/kg氟康唑剂量在统计学上优于安慰剂（OR分别为5.48[95%可信区间，1.81 - 18.94]和2.63[1.18 - 7.02]，以及15.32[1.54 - 54.31]和9.14[1.26 - 142.7]），但这3种剂量的数据在统计学上无显著差异。
鉴于增加氟康唑剂量不会带来更高疗效，反而具有更大的毒性潜力和成本增加，因此建议在新生儿念珠菌预防中使用最低氟康唑剂量（3mg/kg）。
