Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants

Abstract

Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of most of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.

Duration and intensity of fluconazole for prophylaxis in preterm neonates: a meta-analysis of randomized controlled trials

“…The current meta-analysis demonstrates that the use of fluconazole for prophylaxis, compared with no prophylaxis, decreases the risk of invasive fungal infections in preterm infants in NICUs. These findings are consistent with the results of Austin’s study, which pooled data from seven trials and showed that the RR of invasive fungal infections between a systemic antifungal agent and no prophylaxis was 0.41 (95 %CI: 0.27 to 0.61) [ 15 ]. This effect was driven by the studies that employed a 42-day course of prophylaxis (RR: 0.30 ([95 % CI: 0.27–0.61]).…”

“…Prophylactic fluconazole did not significantly reduce death before discharge. This finding is similar to those obtained in other meta-analyses [ 15 , 28 ], but should be carefully explained because the mortality rates in the RCT studies that were included in the meta-analysis were ≤20 % and invasive fungal infections contributed to approximately 20 % of the mortalities [ 29 ]. The previous RCT studies may not have had sufficient power to detect the impact of prophylactic fluconazole on mortality associated with fungal infection due to their relatively small sample sizes (<200 infants in each arm) [ 8 – 11 , 17 ].…”

Duration and intensity of fluconazole for prophylaxis in preterm neonates: a meta-analysis of randomized controlled trials

“…The current meta-analysis demonstrates that the use of fluconazole for prophylaxis, compared with no prophylaxis, decreases the risk of invasive fungal infections in preterm infants in NICUs. These findings are consistent with the results of Austin’s study, which pooled data from seven trials and showed that the RR of invasive fungal infections between a systemic antifungal agent and no prophylaxis was 0.41 (95 %CI: 0.27 to 0.61) [ 15 ]. This effect was driven by the studies that employed a 42-day course of prophylaxis (RR: 0.30 ([95 % CI: 0.27–0.61]).…”

“…Prophylactic fluconazole did not significantly reduce death before discharge. This finding is similar to those obtained in other meta-analyses [ 15 , 28 ], but should be carefully explained because the mortality rates in the RCT studies that were included in the meta-analysis were ≤20 % and invasive fungal infections contributed to approximately 20 % of the mortalities [ 29 ]. The previous RCT studies may not have had sufficient power to detect the impact of prophylactic fluconazole on mortality associated with fungal infection due to their relatively small sample sizes (<200 infants in each arm) [ 8 – 11 , 17 ].…”

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…In addition, fluconazole is administered in high-risk VLBWIs for prophylaxis from Candida infections. A recent meta-analysis of nine RCTs showed that fluconazole is effective in reducing the Candida's colonization rate, the incidence of IC, and its in-hospital and infection-attributed mortality, which is similar to that reported in previous systematic reviews and meta-analyses [133,138,139]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24-72 h), and varying durations (4 to 6 weeks) [111].…”

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…Based on a recent meta-analysis of nine randomized clinical trials on the prophylactic use of fluconazole in VLBWI, fluconazole is effective in reducing the Candida colonization rate, incidence of invasive candidiasis, and the in-hospital and infection-attributed mortality, which is similar to what was reported in previous systematic reviews and meta-analyses [66,76,77]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24 -72 hours), and varying duration (4 to 6 weeks) [61].…”

Duration and intensity of fluconazole for prophylaxis in preterm neonates: a meta-analysis of randomized controlled trials

“…The current meta-analysis demonstrates that the use of fluconazole for prophylaxis, compared with no prophylaxis, decreases the risk of invasive fungal infections in preterm infants in NICUs. These findings are consistent with the results of Austin’s study, which pooled data from seven trials and showed that the RR of invasive fungal infections between a systemic antifungal agent and no prophylaxis was 0.41 (95 %CI: 0.27 to 0.61) [ 15 ]. This effect was driven by the studies that employed a 42-day course of prophylaxis (RR: 0.30 ([95 % CI: 0.27–0.61]).…”

“…Prophylactic fluconazole did not significantly reduce death before discharge. This finding is similar to those obtained in other meta-analyses [ 15 , 28 ], but should be carefully explained because the mortality rates in the RCT studies that were included in the meta-analysis were ≤20 % and invasive fungal infections contributed to approximately 20 % of the mortalities [ 29 ]. The previous RCT studies may not have had sufficient power to detect the impact of prophylactic fluconazole on mortality associated with fungal infection due to their relatively small sample sizes (<200 infants in each arm) [ 8 – 11 , 17 ].…”

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…In addition, fluconazole is administered in high-risk VLBWIs for prophylaxis from Candida infections. A recent meta-analysis of nine RCTs showed that fluconazole is effective in reducing the Candida's colonization rate, the incidence of IC, and its in-hospital and infection-attributed mortality, which is similar to that reported in previous systematic reviews and meta-analyses [133,138,139]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24-72 h), and varying durations (4 to 6 weeks) [111].…”

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…Based on a recent meta-analysis of nine randomized clinical trials on the prophylactic use of fluconazole in VLBWI, fluconazole is effective in reducing the Candida colonization rate, incidence of invasive candidiasis, and the in-hospital and infection-attributed mortality, which is similar to what was reported in previous systematic reviews and meta-analyses [66,76,77]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24 -72 hours), and varying duration (4 to 6 weeks) [61].…”

Duration and intensity of fluconazole for prophylaxis in preterm neonates: a meta-analysis of randomized controlled trials

“…The current meta-analysis demonstrates that the use of fluconazole for prophylaxis, compared with no prophylaxis, decreases the risk of invasive fungal infections in preterm infants in NICUs. These findings are consistent with the results of Austin’s study, which pooled data from seven trials and showed that the RR of invasive fungal infections between a systemic antifungal agent and no prophylaxis was 0.41 (95 %CI: 0.27 to 0.61) [ 15 ]. This effect was driven by the studies that employed a 42-day course of prophylaxis (RR: 0.30 ([95 % CI: 0.27–0.61]).…”

“…Prophylactic fluconazole did not significantly reduce death before discharge. This finding is similar to those obtained in other meta-analyses [ 15 , 28 ], but should be carefully explained because the mortality rates in the RCT studies that were included in the meta-analysis were ≤20 % and invasive fungal infections contributed to approximately 20 % of the mortalities [ 29 ]. The previous RCT studies may not have had sufficient power to detect the impact of prophylactic fluconazole on mortality associated with fungal infection due to their relatively small sample sizes (<200 infants in each arm) [ 8 – 11 , 17 ].…”

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…In addition, fluconazole is administered in high-risk VLBWIs for prophylaxis from Candida infections. A recent meta-analysis of nine RCTs showed that fluconazole is effective in reducing the Candida's colonization rate, the incidence of IC, and its in-hospital and infection-attributed mortality, which is similar to that reported in previous systematic reviews and meta-analyses [133,138,139]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24-72 h), and varying durations (4 to 6 weeks) [111].…”

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

“…Based on a recent meta-analysis of nine randomized clinical trials on the prophylactic use of fluconazole in VLBWI, fluconazole is effective in reducing the Candida colonization rate, incidence of invasive candidiasis, and the in-hospital and infection-attributed mortality, which is similar to what was reported in previous systematic reviews and meta-analyses [66,76,77]. Several prophylactic dosage regimens have been studied, with different dose ranges (from 3 to 6 mg/kg), different dosing intervals (every 24 -72 hours), and varying duration (4 to 6 weeks) [61].…”