Abstract:Objective To assess the efficacy and safety of fluconazole in the prophylaxis of invasive fungal infection in very low birth weight (VLBW) infants. Methods Databases including PubMed, Embase, the Cochrane Library, Wanfang Data, Weipu, and CNKI were searched for randomized controlled trials (RCTs) of prophylactic fluconazole in VLBW infants. Review Manager 5.3 software was used to perform a Meta analysis of the included studies. Results A total of 12 RCTs were included, involving 1 679 VLBW infants. The Meta analysis showed that prophylactic fluconazole significantly reduced the incidence of invasive fungal infection (RR=0.44, 95%CI:0.27-0.71, P < 0.001), the incidence of fungal colonization (RR=0.31, 95%CI:0.24-0.40, P < 0.001), and the mortality during hospitalization (RR=0.74, 95%CI:0.58-0.94, P=0.01) compared with the control group. There were no significant differences between VLBW infants using different doses of fluconazole in the incidence of invasive fungal infection and fungal colonization (P > 0.05). No significant differences were found in the incidence of fluconazole resistance and complications between the fluconazole and control groups (P > 0.05). Conclusions Prophylactic fluconazole can effectively and safely prevent invasive fungal infection in VLBW infants, even at a small dose.
XIA Xu-Hua,LIN Lu,HUA Zi-Yu. Efficacy and safety of fluconazole in prophylaxis of invasive fungal infections in very low birth weight infants: a Meta analysis[J]. CJCP, 2020, 22(5): 446-453.
Kaufman DA. Challenging issues in neonatal candidiasis[J]. Curr Med Res Opin, 2010, 26(7):1769-1778.
[2]
Clerihew L, Lamagni TL, Brocklehurst P, et al. Invasive fungal infection in very low birthweight infants:national prospective surveillance study[J]. Arch Dis Child Fetal Neonatal Ed, 2006, 91(3):F188-F192.
[3]
Boghossian NS, Page GP, Bell EF, et al. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births[J]. J Pediatr, 2013, 162(6):1120-1124.e1.
[4]
Feja KN, Wu F, Roberts K, et al. Risk factors for candidemia in critically ill infants:a matched case-control study[J]. J Pediatr, 2005, 147(2):156-161.
[5]
Xia H, Wu H, Xia S, et al. Invasive Candidiasis in preterm neonates in China:a retrospective study from 11 NICUS during 2009-2011[J]. Pediatr Infect Dis J, 2014, 33(1):106-109.
[6]
Benjamin DK Jr, Stoll BJ, Fanaroff AA, et al. Neonatal candidiasis among extremely low birth weight infants:risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months[J]. Pediatrics, 2006, 117(1):84-92.
[7]
Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neuro-developmental and growth impairment among extremely low-birth-weight infants with neonatal infection[J]. JAMA, 2004, 292(19):2357-2365.
[8]
Cleminson J, Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants[J]. Cochrane Database Syst Rev, 2015, (10):CD003850.
Leonart LP, Tonin FS, Ferreira VL, et al. Fluconazole doses used for prophylaxis of invasive fungal infection in neonatal intensive care units:a network Meta-analysis[J]. J Pediatr, 2017, 185:129-135.e6.
[11]
Ericson JE, Kaufman D, Kicklighter SD, et al. Fluconazole prophylaxis for the prevention of candidiasis in premature infants:a Meta-analysis using patient-level data[J]. Clin Infect Dis, 2016, 63(5):604-610.
Blyth CC, Barzi F, Hale K, et al. Chemoprophylaxis of neonatal fungal infections in very low birthweight infants:efficacy and safety of fluconazole and nystatin[J]. J Paediatr Child Health, 2012, 48(9):846-851.
[14]
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials:is blinding necessary?[J]. Control Clin Trials, 1996, 17(1):1-12.
[15]
Kicklighter SD, Springer SC, Cox T, et al. Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant[J]. Pediatrics, 2001, 107(2):293-298.
[16]
Kaufman D, Boyle R, Hazen KC, et al. Fluconazole prophylaxis against fungal colonization and infection in preterm infants[J]. N Engl J Med, 2001, 345(23):1660-1666.
[17]
Kaufman D, Boyle R, Hazen KC, et al. Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight[J]. J Pediatr, 2005, 147(2):172-179.
[18]
Manzoni P, Stolfi I, Pugni L, et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates[J]. N Engl J Med, 2007, 356(24):2483-2495.
[19]
Parikh TB, Nanavati RN, Patankar CV, et al. Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants[J]. Indian Pediatr, 2007, 44(11):830-837.
Aydemir C, Oguz SS, Dizdar EA, et al. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants[J]. Arch Dis Child Fetal Neonatal Ed, 2011, 96(3):F164-F168.
[22]
Kaufman DA, Cuff AL, Wamstad JB, et al. Fluconazole prophylaxis in extremely low birth weight infants and neurodevelopmental outcomes and quality of life at 8 to 10 years of age[J]. J Pediatr, 2011, 158(5):759-765.e1.
[23]
Benjamin DK Jr, Hudak ML, Duara S, et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants:a randomized clinical trial[J]. JAMA, 2014, 311(17):1742-1749.
[24]
Jannatdoust A, Imani V. The effect of prophylactic intravenous fluconazole on the clinical outcome of preterm infants during hospitalization[J]. Int J Women's Health Reprod Sci, 2015, 3(4):212-216.
[25]
Kirpal H, Gathwala G, Chaudhary U, et al. Prophylactic fluconazole in very low birth weight infants admitted to neonatal intensive care unit:randomized controlled trial[J]. J Matern Fetal Neonatal Med, 2016, 29(4):624-628.
Brion LP, Uko SE, Goldman DL. Risk of resistance associated with fluconazole prophylaxis:systematic review[J]. J Infect, 2007, 54(6):521-529.
[28]
Sarvikivi E, Lyytikäinen O, Soll DR, et al. Emergence of fluconazole resistance in a Candida parapsilosis strain that caused infections in a neonatal intensive care unit[J]. J Clin Microbiol, 2005, 43(6):2729-2735.
[29]
Yoder BA, Sutton DA, Winter V, et al. Resistant Candida parapsilosis associated with long term fluconazole prophylaxis in an animal model[J]. Pediatr Infect Dis J, 2004, 23(7):687-688.