Fluconazole Prophylaxis in Prevention of Symptomatic Candida Vaginitis.

Due to broad spectrum susceptibility of Candida species to fluconazole, its convenience as an oral agent, and predictable patient tolerance and safety, current practice guidelines recommend the use of long-term suppression regimens of fluconazole as prophylaxis for recurrent vulvovaginal candidiasis (RVVC), as well as in abbreviated doses when known trigger factors emerge and inevitable symptomatic episodes are predictable. However, recent concerns of fluconazole-resistant Candida albicans strains may impact fluconazole use, particularly, concerns of overuse. This literature review discusses current recommendations for prophylaxis of vulvovaginal candidiasis with fluconazole.

Fluconazole prophylaxis in preterm infants: a systematic review

ABSTRACT Objective: This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. Methods: This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Results: Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Conclusion: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.

Fluconazole prophylaxis in preterm infants: a systematic review.

OBJECTIVE: This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. METHODS: This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". RESULTS: Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. CONCLUSION: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.

Fluconazole prophylaxis in preterm infants: a multicenter case-controlled analysis of efficacy and safety.

BACKGROUND: Fluconazole prophylaxis has demonstrated efficacy in single and multicenter randomized controlled trials without side effects or emergence of resistance. Additional evidence based on incidence of invasive Candida infections, multicenter data, resistance, and safety is desired. METHODS: We conducted a case-control analysis of efficacy and safety of fluconazole prophylaxis from a multicenter database from a neonatal infection study that included 2017 infants <1250 grams from 95 NICUs. Infants receiving intravenous antifungal prophylaxis were pre-identified during enrollment in the parent study. For each infant receiving antifungal prophylaxis (case), three infants not receiving antifungal (controls) were matched by birth weight (± 50 g), by gestational age (± 1 week), gender, and study site. RESULTS: Fluconazole prophylaxis was administered to 127 patients [754 ± 163 g birth weight (BW) and 25.4 ± 1.7 weeks gestational age (GA)] and were compared with 399 control patients (756 ± 163 g BW and 25.5 ± 1.8 weeks GA). Invasive Candida infection occurred in 0.8% (1 of 127) infants who received fluconazole prophylaxis compared with 7.3% (29 of 399) of matched controls (p = 0.006). Candida bloodstream infection occurred in 0.8% (1 of 127) fluconazole prophylaxis infants compared with 5.5% (22 of 399) of matched controls (p = 0.02). There were no differences in late-onset sepsis due to gram-positive or gram-negative organisms, focal bowel perforation, necrotizing enterocolitis, cholestasis, or overall mortality. CONCLUSION: Fluconazole prophylaxis is safe and efficacious in preventing invasive Candida infections. Even in NICUs with a low incidence of invasive Candida infections, antifungal prophylaxis for high-risk infants is a proven and safe opportunity for infection prevention in these patients.

Adrenocortical insufficiency is not a problem in preterm infants treated with antifungal prophylaxis with fluconazole.

AIM: Fluconazole prophylaxis of invasive fungal infections is a cornerstone of neonatal care, but in vitro studies have shown that it inhibits corticosteroid production. This study assessed whether preterm infants demonstrated an association between fluconazole administration, and its duration, and symptoms of adrenocortical insufficiency. METHODS: We compared two groups who were treated before and after we introduced the use of fluconazole to our neonatal intensive care unit. Infants with a gestational age of ≤27 weeks or with a birth weight of ≤750 g were considered for the retrospective analysis. In order to assess whether the duration of prophylaxis was related to adrenocortical insufficiency, regression models were performed in all preterm infants in the fluconazole group. RESULTS: The fluconazole group (n = 37) and nonfluconazole group (n = 41) were compared. No differences were found in the percentage of infants with symptoms of adrenocortical insufficiency, such as hypotension or need of vasopressor therapy. The incidence of hypotension and the use of vasopressor therapy were not related to duration of fluconazole prophylaxis. CONCLUSION: Fluconazole and it duration were not associated with the incidence of symptoms related to adrenocortical insufficiency. Further prospective trials are needed to better define the relationship between fluconazole and adrenocortical insufficiency.

Changes in the incidence of candidiasis in neonatal intensive care units.

OBJECTIVE: Neonatal invasive candidiasis is associated with significant morbidity and mortality. We describe the association between invasive candidiasis and changes in use of antifungal prophylaxis, empirical antifungal therapy, and broad-spectrum antibacterial antibiotics over time. METHODS: We examined data from 709,325 infants at 322 NICUs managed by the Pediatrix Medical Group from 1997 to 2010. We determined the cumulative incidence of invasive candidiasis and use of antifungal prophylaxis, broad-spectrum antibacterial antibiotics, and empirical antifungal therapy by year. RESULTS: We identified 2063 (0.3%) infants with 2101 episodes of invasive candidiasis. Over the study period, the annual incidence of invasive candidiasis decreased from 3.6 episodes per 1000 patients to 1.4 episodes per 1000 patients among all infants, from 24.2 to 11.6 episodes per 1000 patients among infants with a birth weight of 750-999 g, and from 82.7 to 23.8 episodes per 1000 patients among infants with a birth weight <750 g. Fluconazole prophylaxis use increased among all infants with a birth weight <1000 g (or <1500 g), with the largest effect on birth weights <750 g, increasing from 3.8 per 1000 patients in 1997 to 110.6 per 1000 patients in 2010. The use of broad-spectrum antibacterial antibiotics decreased among all infants from 275.7 per 1000 patients in 1997 to 48.5 per 1000 patients in 2010. The use of empirical antifungal therapy increased over time from 4.0 per 1000 patients in 1997 to 11.5 per 1000 patients in 2010. CONCLUSIONS: The incidence of invasive candidiasis in the NICU decreased over the 14-year study period. Increased use of fluconazole prophylaxis and empirical antifungal therapy, along with decreased use of broad-spectrum antibacterial antibiotics, may have contributed to this observation.

Prevention of Invasive Candida Infections in the Neonatal Intensive Care Unit / 소아감염

Invasive Candida infections (ICI) have become the third most common cause of late-onset infection among premature infants in the neonatal intensive care unit (NICU). Risk factors include birth weight less than 1,000 g, exposure to more than two antimicrobials, third generation cephalosporin exposure, parenteral nutrition including lipid emulsion, central venous catheter, and abdominal surgery. Candida colonization of the skin and gastrointestinal tract is an important first step in the pathogenesis of invasive disease. Strict infection control measures against the infection should be done in the NICU. The following practices are likely to contribute to reducing the rate of ICI: (1) restriction of broad-spectrum antibiotics, antacids and steroid; (2) introduction of early feeding and promoting breast milk. Fluconazole prophylaxis may be an effective control measure to prevent Candida colonization and infections in individual units with high incidence of fungal infection. In addition, there is a need of further data including the development of resistant strains and the effect on long-term neurodevelopmental outcomes of infants exposed to drugs before the initiation of routine application of antifungal prophylaxis in the NICU.

Effect of Fluconazole Prophylaxis to Control Candida Infection in High-Risk Preterm Infants / 대한주산의학회잡지

OBJECTIVE: Candida species are becoming one of the most common pathogens associated with nosocomial infection in the neonatal intensive care units (NICU). This study was undertaken to evaluate the efficacy of fluconazole prophylaxis (FP) to control candida infection in high-risk preterm infants. METHODS: A prospective, randomized clinical trial was conducted over a 17-month period (Aug. 2008-Dec. 2009) in very low birth weight (VLBW) infants who were admitted to NICU of Dongsan Medical Center, Keimyung University. The 55 VLBW infants with mechanical ventilation, central vascular access and parenteral nutrition at early time of life were enrolled for this study. The infants were randomly assigned to FP and control group in the first three days of life. Fluconazole was administered by intravenous route for 4- to 6-week after birth at dose of 3 mg per kilogram of body weight. All enrolled infants underwent weekly surveillance culture for candida colonization. RESULTS: The 28 infants with FP and the 27 control infants were similar in comparison of the perinatal parameters such as gestational age, birth weight and antenatal steroid therapy. And also, there were no differences between the two groups in terms of presence of common risk factors for invasive candida infection. During prophylactic period, candida colonization was identified in 5 infants of the fluconazole group and 15 infants of the control group (17.9% vs. 55.6%; P<0.005). And also candida sepsis was more frequently developed in the control group, but the result was not significant. No differences in liver function tests after prophylactic period were noted. Between two groups, prognostic factors such as duration of stay in hospital, combined diseases and mortality were not different. CONCLUSIONS: FP may help to control candida infection in high-risk preterm infants, but large scaled multicenter studies including development of resistant strains are necessary before initiation of routine prophylaxis.

Fluconazole prophylaxis in high-risk, very low birth weight infants / 소아과

PURPOSE: Fluconazole prophylaxis for very low birth weight (VLBW) infants has been shown to reduce invasive fungal infection and its mortality. This study aims to evaluate the effect of fluconazole prophylaxis in VLBW infants on the incidence and mortality of fungal infection. METHODS: VLBW infants with endotracheal intubation and central vascular access admitted to the Neonatal Intensive Care Unit (NICU) at Chonnam University Hospital were enrolled. Twenty eight infants of 7-month baseline period from January to July 2005 ('non-fluconazole group') were compared with 29 infants of a 7-month fluconazole period from January to July 2006 ('fluconazole group'). RESULTS: Gestational age, birth weight, sex, mode of delivery, frequency of twin pregnancy, chorioamnionitis, antenatal steroid and rupture of membranes were similar between the fluconazole and non- fluconazole groups. The rate of extremely low birth weight (ELBW) infants, frequency and duration of prophylactic antibiotics, total parenteral nutrition and umbilical catheters, duration of intralipid, mechanical ventilation and nasal continuous positive airway pressure (CPAP) were also not significant. However, frequency of percutaneous central venous catheterization (PCVC) and intralipid administration, and duration of PCVC were significant between the two groups. The overall incidence and mortality of fungal infection were not different between the two groups. Although the Malassezia infection was increased in the fluconazole group (P<0.05), candida was significantly decreased compared to the non- fluconazole group (P<0.05). CONCLUSION: Fluconazole prophylaxis in high risk VLBW infants decreased the candida infection significantly. Antifungal prophylaxis is recommended in terms of cost effectiveness, but further study is needed to clarify the reason for the increase of Malassezia infection.