Effect Of Fluconazole Prophylaxis Research Articles

Effectiveness of Fluconazole Prophylaxis in a Targeted High-Risk Group in a Surgical Intensive Care Unit.

Background: Candidemia is an important nosocomial infection in intensive care units (ICUs), with total parenteral nutrition (TPN) a well-recognized risk factor. Antifungal prophylaxis may be an effective intervention to prevent candidemia in high-risk patients. In this report, the effectiveness of fluconazole prophylaxis was examined in patients located in a combined surgical-neurosurgical ICU serving an urban Level 1 trauma center who were receiving prolonged courses of TPN. Methods: Fluconazole was administered prophylactically for patients receiving TPN for more than six days. Rates of candidemia during the intervention were compared with those prior to the intervention. Results: During the 27-month pre-intervention period, seven episodes of candidemia occurred during 1,277 days of parenteral nutrition therapy. During the 17-month post-intervention period, there were zero episodes during 852 days of therapy (p = 0.03). Similarly, during the pre-intervention period, there were six episodes of candidemia during 867 high-risk days of therapy, compared with zero during 643 days of high-risk therapy in the post-intervention period (p = 0.04). The rates of bacteremia did not change, and emergence of fluconazole-resistant Candida species was not evident. Conclusions: At our surgical ICU, this fluconazole prophylaxis was associated with a significant decrease in the number of patients with candidemia, without emergence of resistant species.

Fluconazole Prophylaxis of Candida Infections in Preterm Neonates

Abstract Infections belong to the most serious health problems in neonates. Invasive candidiases are one of the leading causes of mortality and morbidity in Neonatal intensive care units (NICUs). A more cautious approach is adequate when dealing with fungal infections in premature neonates. Sometimes it is necessary to cure an infection at the very beginning just before manifestation of clinical symptoms. Neonatal colonization due to Candida albicans or non-albicans Candidae predisposes to invasive candidiasis. Pregnancies complicated by preterm delivery should be considered for screening and treatment of maternal Candida colonization to decrease the occurrence of neonatal fungal colonization and its consequences. It is important to prevent infection to spread among patients and avoid complications. Prophylaxis in neonates must be safe and effective. Most authors prefer selective prophylaxis. Fluconazole is the drug of choice for prophylaxis in extremely low birth weight (ELBW) neonates. The prophylaxis is beneficial especially in NICUs with high rates of invasive candidiases. The authors describe benefits and trends in prophylaxis. They also summarize evidence on timing, dosing, and effect of fluconazole prophylaxis.

Preventive effect of Fluconazole prophylaxis on invasive fungous infections of premature infants

Objective To explore the preventive effect of Fluconazole on invasive fungous infections in premature infants. Methods Two hundred and thirty-four cases of preterm infants hospitalized in Jiangmen Central Hospital from Feb.2008 to Oct.2013 were analyzed by retrospective study.The subjects were divided into 3 groups based on whether Fluconazole was used and it was used orally or intravenously for the prevention of invasive fungous infections in premature infants.The Fluconazole prophylaxis was not given to group A, whereas oral Fluconazole prophylaxis[6 mg/(kg·times), every other day] and intravenous Fluconazole prophylaxis [3 mg/ (kg·times), once every 3 days] were applied in group B and group C. The incidence of invasive fungous infections and the clinical effects of Fluconazole on the 3 groups were evaluated and compared. Results The number of cases analyzed in the study were 53, 115 and 66 cases in group A, group B and group C, respectively.There were no significant differences between the 3 groups in terms of gender, gestational age, birth weights, length of hospitalization, intravenous nutrition, and number of peripherally inserted central catheter, antibiotics and invasive mechanical ventilation use days (all P>0.05). The incidences of invasive fungal infections were 11.32% (6/53 cases), 6.96% (8/115 cases) and 0 in group A, group B and group C, respectively.The prophylaxis effects between the 3 groups were significantly different (χ2=7.078, P=0.029). Group A and group B were not significantly different (χ2=0.905, P=0.342), but group C was better than group A and group B, and the differences were significant (P=0.007, 0.028). Conclusions Prevention of invasive fungous infections by intravenous Fluconazole has good curative effects, and which can be used as the first choice. Key words: Fluconazole; Fungus; Prophylaxis; Infant, newborn

Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial.

Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. Fluconazole (6 mg/kg of body weight) or placebo. The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes-defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18 to 22 months corrected age. Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%-22%) vs 21% in the placebo group (95% CI, 15%-28%; odds ratio, 0.73 [95% CI, 0.43-1.23]; P = .24; treatment difference, -5% [95% CI, -13% to 3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%-6%]) vs the placebo group (9% [95% CI, 5%-14%]; P = .02; treatment difference, -6% [95% CI, -11% to -1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole, 31% [95% CI, 21%-41%] vs placebo, 27% [95% CI, 18%-37%]; P = .60; treatment difference, 4% [95% CI, -10% to 17%]). Among infants with a birth weight of less than 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely low-birth-weight infants. clinicaltrials.gov Identifier: NCT00734539.

Fluconazole prophylaxis is associated with a decreased rate of coagulase-negative Staphylococcal infections in a subset of extremely low birth weight neonates.

Fluconazole prophylaxis is being used efficaciously in the neonatal intensive care unit (NICU) for fungal prophylaxis in very low birth weight and extremely low birth weight (ELBW) neonates. Little is known about the effect of fluconazole prophylaxis on bacterial infections. The purpose of this study was to examine that issue in a subset of ELBW, those weighing ≤900 g at birth. This is a retrospective study conducted in a level III NICU at state-designated children hospital in New Jersey (USA). We examined the data from our records of neonates ≤ 900 g birth weight during the period March 1, 2007-February 28, 2011. Inclusion in the study was all infants ≤ 900 g before (n = 67) and after (n = 81) the institution of fluconazole prophylaxis. Fluconazole prophylaxis was accompanied by a significant decrease in both the rate and number of days of bacterial infections as well as co-infections. We found that the incidence of coagulase-negative Staphylococcus (CONS) decreased from 46.2 to 24.7 % (OR 2.63; 95 % CI 1.31-5.27). Similarly, days of infection also decreased significantly (p < 0.0001). These data suggest that fluconazole prophylaxis may be associated with a reduction in CONS infections in that subset of ELBW neonates.

AO-44. Effect of fluconazole prophylaxis to control Candida infection in high-risk preterm infants

AO-44. Effect of fluconazole prophylaxis to control Candida infection in high-risk preterm infants

Fluconazole Prophylaxis in High-Risk Neonates

To evaluate the literature regarding the use of fluconazole prophylaxis in high-risk neonates. Literature was accessed through MEDLINE (February 2001-August 2009) using the search terms fluconazole and prophylaxis, with limits for age group (ie, birth-18 y). Reference citations from identified articles were also reviewed. DATA SELECTION AND DATA EXTRACTION: All prospective and retrospective studies in English identified from MEDLINE were evaluated. Critically ill neonates possess a number of risk factors that predispose them to fungal colonization with Candida spp. In many cases, colonization may progress to invasive systemic infections despite efforts aimed at early diagnosis and treatment. Because of its success among immunocompromised patients, fluconazole prophylaxis has been suggested as a possible approach for reducing the rates of both colonization and invasive fungal infections among at-risk neonates. To date, 4 prospective randomized controlled trials and 8 retrospective cohort studies have examined fluconazole prophylaxis in neonates. Although fluconazole prophylaxis appears to reduce the rates of colonization and invasive fungal infections, no trial in this review was able to demonstrate a significant difference in long-term morbidity or mortality. Concerns also remain regarding the adverse effects associated with prolonged exposure to fluconazole therapy. Lack of standardized study designs and treatment regimens also limit widespread recommendation for the use of fluconazole prophylaxis in clinical practice. While it may be beneficial for critically ill neonates with certain predisposing risk factors (eg, central venous access, sustained exposure to broad-spectrum antibiotics, or units with significantly high incidence of invasive fungal infections), existing research does not support the use of fluconazole prophylaxis based on birth weight or gestational age alone. Multifactor analysis evaluating the effect of fluconazole prophylaxis is necessary to establish which neonates would benefit from this practice.

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

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 nonfluconazole 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

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

In an effort to bring novel diagnostic and prognostic biomarkers or even potential targets for vaccine design for systemic candidiasis (SC) into the open, a systematic proteomic approach coupled with bioinformatic analysis was used to decode the serological response to Candida wall immunome in SC patients. Serum levels of IgG antibodies against Candida wall-associated proteins (proteins secreted from protoplasts in active wall regeneration, separated by two-dimensional gel electrophoresis, and identified by mass spectrometry) were measured in 45 SC patients, 57 non-SC patients, and 61 healthy subjects by Western blotting. Two-way hierarchical clustering and principal component analysis of their serum anti-Candida wall antibody expression patterns discriminated SC patients from controls and highlighted the heterogeneity of their expression profiles. Multivariate logistic regression models demonstrated that high levels of antibodies against glucan 1,3-beta-glucosidase (Bgl2p) and the anti-wall phosphoglycerate kinase antibody seropositivity were the only independent predictors of SC. Receiver operating characteristic curve analysis revealed no difference between their combined evaluation and measurement of anti-Bgl2p antibodies alone. In a logistic regression model adjusted for known prognostic factors for mortality, SC patients with high anti-Bgl2p antibody levels or a positive anti-wall enolase antibody status, which correlated with each other, had a reduced 2-month risk of death. After controlling for each other, only the seropositivity for anti-wall enolase antibodies was an independent predictor of a lower risk of fatality, supporting that these mediated the protective effect. No association between serum anti-cytoplasmic enolase antibody levels and outcomes was established, suggesting a specific mechanism of enolase processing during wall biogenesis. We conclude that serum anti-Bgl2p antibodies are a novel accurate diagnostic biomarker for SC and that, at high levels, they may provide protection by modulating the anti-wall enolase antibody response. Furthermore serum anti-wall enolase antibodies are a new prognostic indicator for SC and confer protection against it. Bgl2p and wall-associated enolase could be valuable candidates for future vaccine development.

Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy

The aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy. Sixty-three patients, with malignant head and neck tumor, eligible to receive radiotherapy, entered the study. Thirty-four patients (group A) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients, who received radiotherapy alone (group B). The two groups were similar in terms of patients and radiotherapy characteristics. Smear to test for Candida carriage was taken before and after radiotherapy. Oral candidiasis was diagnosed using the criteria described before. Oral mucositis was recorded according to EORTC/RTOG criteria. A significant reduction of severe mucositis at the end of radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017) was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a significant reduction of Candida carriage of 40.7% (p=0.001). Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients. The current study provides data on the build of a randomized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy.

Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy.

To investigate the utility of blood culture of invasive fungal infections in patients with haematological malignancies, an autopsy survey was conducted in 720 patients who were treated between 1980 and 1999. We identified 252 patients with invasive mycosis. These included Candida (n = 94), Aspergillus (n = 91), Zygomycetes (n = 34), Cryptococcus (n = 7), Trichosporon (n = 11), Fusarium (n = 1), and unknown fungi (n = 20). Of the 94 patients with invasive candidiasis, 20 had positive blood cultures. Of the 11 patients with invasive trichosporonosis, seven had positive blood cultures. The sensitivities of blood cultures were 1.1%, 0% and 14% for detecting invasive aspergillosis, zygomycosis and cryptococcosis respectively. Multiple regression analysis showed a significant correlation between results of Candida blood cultures and some variables, including prophylactic use of absorbable antifungals (P = 0.0181) and infection by Candida albicans (P = 0.0086). The sensitivity of blood cultures decreased when patients received antifungal chemoprophylaxis. Unless these agents are inactivated in culture bottles, conventional blood cultures might produce false-negative results.

Effects of Fluconazole Singly and in Combination with 5-Fluorocytosine or Amphotericin B in the Treatment of Cryptococcal Meningoencephalitis in an Intracranial Murine Model

In this study we developed a highly reproducible intracranial murine model of cryptococcosis. Mice (Balb/c, 5-7 weeks old) were challenged intracranially and treated with intermediate (30 mg/kg) or high (90 mg/kg) dose fluconazole, and amphotericin B (0.75 mg/kg), administered singly or in combination with flucytosine (100 mg/kg). Survival and brain CFU analyses were performed. Effect of fluconazole prophylaxis was also determined. Our data show that the developed model mimics clinical signs of cryptococcal meningitis. In single treatment, fluconazole (30 mg/kg) was more efficacious than amphotericin B or flucytosine (P <0.0001). Combination treatment led to significantly increased anticryptococcal activity, which was highest for high dose fluconazole + flucytosine (P <0.0001). However, no significant difference was observed between high dose fluconazole treatment with and without flucytosine (P >0.05). Fluconazole prophylaxis led to a significant decrease in brain CFU. In conclusion, high dose fluconazole administered post-infection, or as prophylaxis, may be highly efficacious in the treatment and prevention of meningoencephalitis.