Kaufman D et al.2929 Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz LG. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med. 2001;345:1660-6.
|
2001 |
Clinical trial randomized, blinded, placebo controlled |
50 NB < 1000 g in placebo group 50 NB < 1000 g in Fluconazol group |
Colonization IC Mortality |
p < 0.001 p = 0.008 p = 0.22 |
Difference in risk 0.18 (95% CI 0.15-0.22) 0.20 (95% CI 0.04-0.36) - |
A-I |
Uko Set al.2121 Uko S, Soghier LM, Vega M, et al. Targeted short-term fluconazole prophylaxis among very low birth weight and extremely low birth weight infants. Pediatrics. 2006;117:1243-52.
|
2006 |
Observational, comparative study, pre and post exposure |
206 NB < 1500 g no prophylaxis 178 NB < 1500 g - prophylaxis |
CI (after 3o day) Mortality |
p = 0.07 p = 0.644 |
OR - 0.166 (95% CI: 0.033-0.709) OR: 0.795; (95% CI: 0.301-2.102) |
A-II |
Manzoni P et al.2222 Manzoni P, Arisio R, Mostert M, et al. Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study. Pediatrics. 2006;117:e22-32.
|
2006 |
Retrospective comparative study pre and post exposure |
240 NB < 1500 g - no prophylaxis 225 NB < 1500 g prophylaxis |
IC Colonization Mortality |
p < 0.0001 p = < 0.001 p = 0.44 |
RR - 0.233 (95% CI 0.113-0.477) RR - 0.406 (95% CI 0.273-0.605) - |
A-II |
Manzoni P et al.3232 Manzoni P, Stolfi I, Pugni L, et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med. 2007;356:2483-95.
|
2007 |
Clinical trial randomized, blinded, placebo controlled |
106 NB < 1500 g in placebo group 112 NB < 1500 g in Fluconazol 6 mg/kg group 104 NB < 1500 g in Fluconazol 3 mg/kg group |
Colonization Placebo × Fluconazol (3 and 6 mg/kg) IC Placebo × Fluconazol (3 and 6 mg/kg) Overall mortality |
p < 0.001 p = 0.001 p = 1 |
RR - 0.30 (95% CI 0.18-0.51) RR = 0.25 (95% CI 0.10-0.59) RR = 0.88 (95% CI 0.10-0.59) |
A-I |
Parikh TB et al.3030 Parikh TB, Nanavati RN, Patankar CV, et al. Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants. Indian Pediatr. 2007;44:830-7.
|
2007 |
Clinical trial randomized, blinded, placebo controlled |
60 NB < 1500 g in placebo group 60 NB < 1500 g in prophylaxis group |
Colonization IC Mortality |
p = 0.003 p = 0.835 p = 1 |
30 (50%) in placebo group and 11 (19%) in fluconazole group 15 (25%) in placebo group and 16(26.7%) in fluconazole group 17 in placebo group 17 in fluconazole group |
B-I |
Weitkamp J-H et al.2323 Weitkamp JH, Ozdas A, LaFleur B, Potts AL. Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure. J Perinatol. 2008;28:405-11.
|
2008 |
Comparative study, pre and post exposure |
44 NB < 750 g or < 26 GA - no prophylaxis 42 NB < 750 g or < 26 weeks of GA in Prophylaxis |
IC |
p = 0.004 |
9 cases in 44 infants (20%) No cases in 42 infants |
B-II |
Healy CM et al.2424 Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole resistant Candida species. Pediatrics. 2008;121:703-10.
|
2008 |
Comparative study, pre and post exposure |
3012 NB - no prophylaxis 6393 NB: 47 NB ≥ 1.000 g + 262 NB < 1000 g in prophylaxis (2002-2006) |
CI IC associated Mortality Overall mortality |
p = 0.05 p = 0.004 p = 0.13 |
19 IC in pre prophylaxis group (0.6%) and 22 IC in pos-prophylaxis group (0.3%) 4 (21%) in pre prophylaxis group and none in pos prophylaxis group 19% (40 of 206 NB) to 15% (65 of 448 NB) |
B-II |
Rueda K et al.2525 Rueda K, Moreno MT, Espinosa M, Saez-Llorens X. Impact of routine fluconazole prophylaxis for premature infants with birth weights of less than 1250 grams in a developing country. Pediatr Infect Dis J. 2010;29:1050-2.
|
2010 |
Comparative study, pre and post exposure |
271 NB < 1250 g - no prophylaxis 252 RN < 1250 g in prophylaxis |
IC Overall Mortality IC associated Mortality |
p = 0.001 p < 0.05 p > 0.05 |
OR = 0.13 (95% CI 0.03-0.47) 6% × 1% 76% × 67% |
A-II |
Rolnitsky A et al.2727 Rolnitsky A, Levy I, Sirota L, Shalit I, Klinger G. Targeted fluconazole prophylaxis for high-risk very low birth weight infants. Eur J Pediatr. 2012;171:1481-7.
|
2012 |
Retrospective cohort with historical controls |
130 RN < 1000 g, or risk factors - Fluconazol prophylaxis 319 historical controls with no prophylaxis |
IC |
p = 0.016 |
OR = 0.05 (95% CI 0.005-0.52) |
A-II |
Benjamin Jr DK et al.3131 Benjamin DK, Hudak ML, Duara S, et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial. JAMA. 2014;311:1742-9.
|
2014 |
Multicentric clinical trial randomized, blinded, placebo controlled |
188 RN < 750 g in Fluconazol prophylaxis 173 RN < 750 g in placebo |
IC < 49 days IC before discharge Mortality < 49 days Mortality before discharge Neurodevelopmental impairment |
p = 0.02 p = 0.02 p = 0.98 p = 0.84 p = 0.60 |
Difference −6 (CI 95% −11 to −1) Difference −7 (CI 95% −12 to −1) Difference 0 (CI 95% −7 to −7) Difference −1 (CI 95% −9 to 7) Difference 4 (CI 95% −10 to 17) |
A-I |
Cetinkaya M et al.2828 Cetinkaya M, Ercan TE, Saglam OK, Buyukkale G, Kavuncuoglu S, Mete F. Efficacy of prophylactic fluconazole therapy in decreasing the incidence of Candida infections in extremely low birth weight preterm infants. Am J Perinatol. 2014;31:1043-8.
|
2014 |
Cohort - pre-post intervention |
Prophylaxis: 90 NB < 1.000 g No prophylaxis: 107 NB < 1.000 g |
IC |
p = 0.03 |
Prophylaxis: none IC Control: 5 (4.7%) IC |
A-II |
Kaufman D et al.2626 Kaufman DA, Morris A, Gurka MJ, Kapik B, Hetherington S. Fluconazole prophylaxis in preterm infants: a multicenter case-controlled analysis of efficacy and safety. Early Hum Dev. 2014;90(Suppl. 1):S87-90.
|
2014 |
Multicenter case-control |
Casos 127 RN < 1250 g receberam fluconazol Controls; 399 RN < 1250 g sem profilaxia |
IC Candida Bloodstream Infection |
p = 0.006 p = 0.02 |
1 (0.8%) of 127 NB 29 (7.3%) of 399 NB 1 (0.8%) of 127 NB 22 (5.5%) of 399 NB |
A-II |