Prophylactic Use Of Fluconazole Research Articles

Prophylactic fluconazole protocol in very low birth weight infants: invasive candidiasis prevention in a Latin American neonatal intensive care unit.

To evaluate the effect of prophylactic fluconazole for very low birth weight infants (VLBWI) in a neonatal intensive care unit (NICU) with a 7.8% incidence of invasive candidiasis (IC). Interventional pre-post cohort study comparing 2 years with and without fluconazole prophylaxis protocol (2016-2018 = 228 infants and 2019-2021 = 125 infants). Fluconazole was administered to all extremely low birth weight infants (ELBWI) and infants with BW 1001-1500 g with risk factors or positive carrier cultures. Liver function tests were performed weekly. The incidence of IC decreased from 7.8% to 2.4% (OR:0.3, p = 0.05) with the use of prophylactic fluconazole for VLBWI and in ELBWI decreased from 16,7% to 3,7% (OR:0.1, p = 0.04). No significant differences were seen in mortality. Fluconazole is a safe, effective, and feasible strategy to prevent IC in a Latin American country.

Detection of ERG11 Overexpression in Candida albicans isolates from environmental sources and clinical isolates treated with inhibitory and subinhibitory concentrations of fluconazole.

Candida species can cause serious infection in patients with changes in defence mechanisms and/or when anatomical barriers are compromised. Mutations and overexpression in the ERG11 gene are described as molecular mechanisms of azole resistance. Information is limited on these mechanisms in the presence of subinhibitory concentrations of fluconazole. This study aimed to evaluate the expression of ERG11 gene from Candida albicans isolates, from clinical and hospital environments, in the absence and presence of inhibitory and subinhibitory concentrations of fluconazole. The American Type Culture Collection 10231 strain, five clinical isolates and three isolates from hospital environment colonisation were exposed to inhibitory and subinhibitory concentrations of fluconazole. Susceptibility tests were performed according to EUCAST 7.1 guidelines, and the relative expression analysis of ERG11 was performed by qPCR. Differences in response to fluconazole concentrations were observed, with the exception only one clinical isolate when treated with 1/4 of the FLU-minimum inhibitory concentration (MIC). All the other isolates, regardless of the isolation source, had an increase in expression. The overexpression occurred in a very broad range, from 1.086 to 126.105 times. In general, treatment with the highest dose of fluconazole (MIC) was the one that most influenced the ERG11 expression, followed by treatments with 1/2 and 1/4 MIC. The increased expression of ERG11 by Calbicans in the presence of different concentrations of fluconazole is relevant, raising concerns in the care and cleaning of the hospital environment and the prophylactic use of fluconazole that could lead to the selection of potential azole-resistant isolates.

Invasive Fungal Infections in the Pediatric Intensive Care Unit.

Invasive Fungal Infections in the Pediatric Intensive Care Unit.

Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

Fluconazole Prophylaxis in Neonates (Non-Systematic) Literature Review

Background: Nosocomial infection remains an important contributing factor for morbidity and mortality in neonates. Coagulase-negative staphylococci have emerged as the predominant pathogens of late onset sepsis. This is followed by staphylococcus aurous, gram negative bacilli, and fungi. Old studies noted that mortality due to candidemia was higher in infants weigh less than 2000 g after being exposed to risk factors. The prophylactic use of fluconazole for the prevention of IC in extremely low birth weight was first reported in 2001. Methods: Current guidelines from Europe and North America that refer to the treatment of fungal infections are included. Literature search was performed using Medline, Scopus and Cochrane Central Register of Controlled Trials through March, 2016. Conclusion: Mortality was not different in early studies. However, recent studies concluded that mortality was reduced in the fluconazole arms. Risk-based approach towards fluconazole prophylaxis seems to be safe and effective.

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 and selective digestive decontamination for prevention of Candida infection in high risk critically ill patients

ObjectiveInvasive fungal infections are common in critically ill patients specially those on prolonged mechanical ventilation. Fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant and other immunocompromized patients. This study aimed to evaluate prophylactic use of fluconazole and selective digestive decontamination (SDD) in the prevention of invasive Candida infections in high risk critically ill patients. DesignA prospective, randomized, placebo-controlled trial. SettingCritical care department, Main Alexandria University Hospital. PatientsSeventy five critically ill patients with anticipated prolonged mechanical ventilation. MethodsThey were randomly assigned to three groups; control group, SDD group, and SDD+fluconazole according to the type of the drug they had received. Cultures were obtained after 5, 10, and 15days. End point was 15days from admission or the occurrence of Candida infection. ResultsIn a time-to-event analysis, the SDD+fluconazole group showed an absolute risk reduction of 48% when compared to the control group, and 28% when compared to the SDD group. The number needed to treat was 2.08 in the SDD+Fluconazole group, while in the SDD group it was 5. ConclusionSDD+fluconazole safely and effectively decreased the incidence of Candida infections in the high-risk, critically ill patients.

European survey on the use of prophylactic fluconazole in neonatal intensive care units

Neonatal fungal infections are associated with substantial mortality and morbidity. Although prophylactic use of several antifungals has been proposed, this practice remains controversial. In order to evaluate the use of fluconazole prophylaxis in European NICUs, we conducted a cross-sectional survey by means of a structured questionnaire that was sent to European level II and III neonatal intensive care units, over a 9-month period, as part of a neonatal research FP7 European project. A total of 193 questionnaires from 28 countries were analysed. Use of antifungal prophylaxis was reported by 55% of the responders, and the most frequently used antifungal agent was fluconazole (92%). Main indications for prophylaxis were low gestational age (<28 weeks) and birth weight (<1,000 g). A dose of 3 mg/kg was used in 66% of NICUs using fluconazole, with an administration interval of 72 h in 52% of them. All responders acknowledged the need for additional trials on the efficacy of prophylactic fluconazole. Non-users of fluconazole prophylaxis were more likely to be influenced by the local incidence of candidiasis, the risk of increasing antifungal resistance and the absence of specific recommendations by paediatric societies. Conclusions: Major concerns about the use of fluconazole prophylaxis include its efficacy, the risk of emergence of resistant species and the absence of clear consensus to support routine use. Future studies that address these issues will contribute to a more rational use of fluconazole prophylaxis.

Number Needed to Treat in Fluconazole Prophylaxis in the Neonatal Intensive Care Unit

To the Editors: In a recent publication in this journal, Rueda et al1 conducted a study in a developing country and demonstrated that routine prophylactic use of fluconazole at birth versus placebo in 523 neonates less than 1250 g is associated with significant impact on the frequency of documented systemic Candida infection (CI). The control group developed CI in 21 (7.7%), whereas the treatment group had only 3 (1.1%) CI. The benefit of prophylactic fluconazole (PF) to prevent a systemic CI was represented by the number needed to treat (NNT) with a nominal value of 7 according to Rueda et al.1 This measure is calculated on the inverse of the absolute risk reduction.2 NNT of 7 means that it is necessary to treat 7 neonates with PF to prevent 1 CI. This NNT is calculated incorrectly. Considering the absolute risk reduction of 6.6% (7.7% − 1.1%), the NNT should be 15.2 (calculated by 1/6.6%) instead of 7. Although this error does not change the statistical significance of the benefit of fluconazole in the study of Rueda et al (P = 0.007),1 for pharmacoeconomic analysis studies, this error has an important impact. There is scant information from developing countries about PF in neonates,1 and the estimated NNT of 15.2 is acceptable. A broader view on the updated systematic review results of the Cochrane meta-analysis of 5 of 8 eligible trials on “systemic antifungal agents prophylatic in low birth weight infants,” issue 12, 2010,3 revealed that NNT for PF is in line with the confidence intervals of PF, with significant reduction in the risk of invasive fungal infection in the infants who received prophylaxis (NNT = 11; 95% confidence interval, 7–33).3 Although it requires confirmation from future studies, the prophylactic use of fluconazole in premature infants of lower weight, with higher natural risk of systemic candidiasis (extremely low birth weight <1000 g),4 suggests a greater benefit: the calculated NNT is 2.68 for fungal colonization (22% PF × 60% placebo) and NNT of 5 for systemic fungal infection (0% PF × 20% placebo).4 Moreover, the systematic reviews still show a nonsignificant decrease in the risk of death before hospital discharge (typical relative risk, 0.74 [95% confidence interval, 0.51–1.09]).3 To date, the only untoward effects reported with fluconazole use in preterm infants are reversible elevations in hepatic enzymes or bilirubin, without sequelae.5 ACKNOWLEDGMENT The authors thank Dr. Débora Cristina Raulik Shieh of Universidade Federal do Paraná for her assistance in the preparation of the manuscript. Huei Hsin Shieh, MD Pediatric Intensive Care Unit University Hospital University of Sao Paulo Silvia Maria Ibidi, MD, MSc Neonatal Intensive Care Unit University Hospital University of Sao Paulo Alfredo Elias Gilio, MD, PhD Division of Pediatrics University Hospital University of Sao Paulo Sao Paulo, Brazil

A systematic review of oral fungal infections in patients receiving cancer therapy

The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections. Thirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization. For all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care. There is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents.

Aspergillosis of Biliary Tract After Liver Transplantation: A Case Report

We reported a case of aspergillosis presented as cholangitis in a patient after liver transplantation, even with prophylactic use of fluconazole. The patient had multiple predisposing factors, such as leukocytopenia, immunosuppressive drug therapy. He died 2 days after an exploratory laparotomy was carried out. The histopathologic finding of biopsy specimen from biliary tract was positive for Aspergillus. And the pathogen was identified as Aspergillus flavus by mycological culture and PCR. The patient was confirmed as a case of Aspergillosis of biliary tract that was responded poorly to fluconazole. This indicated that azole should have been switched to more effective antifungal agents at earlier stage when the patients responded poorly to the original treatment.

Empiric Antifungal Therapy with Amphotericin B in the Era of Fluconazole Prophylaxis: a Cohort Study in Adults with Acute Myeloid Leukemia Treated within An Institutional Antifungal Policy.

Abstract 1390Poster Board I-412 Purpose:To determine whether fluconazole prophylaxis was effective in decreasing the need for parenteral empiric antifungal therapy in patients with acute myeloid leukemia (AML) and persistent febrile neutropenia or suspected fungal infection at our center. Background:Prophylaxis with fluconazole in patients with severe chemotherapy-related neutropenia has been found to be beneficial in decreasing the need for parenteral antifungal therapy, and preventing superficial and invasive fungal infections and fungal infection-related mortality (Bow et al., Cancer 2002;94:3230-3246). Methods:The records of all patients at our hospital who presented with AML from January 1999 to July 2009 were reviewed retrospectively. As of September 2005 we adopted an institutional antifungal policy consisting of routine antifungal prophylaxis with fluconazole followed by amphotericin B as the first line parenteral agent in the event of persistent fever despite broad spectrum antibiotics or suspected fungal infection. The policy included criteria for switching from amphotericin B to a second line agent (caspofungin) for continued empiric therapy or another agent depending on clinical or laboratory data or suspicion of a particular pathogen. Explicit criteria were also developed for switching to a second line agent including baseline renal function or change in renal function while receiving amphotericin B or other adverse effects such as significant infusion reactions or electrolyte disturbances. Fluconazole was given at a dose of 400 mg daily starting with induction chemotherapy and continued until blood count recovery or switch to parenteral antifungal agent. Results:We identified a total of 170 patients with a median age of 61 years (range 18-89 years), 53 % were female and the median follow-up time was 187 days (range 2-2549 days). Baseline cytogenetics grouped patients into poor risk (40%), standard risk (39%) and favorable risk (10%) categories, with 11% unknown or inconclusive. Two-thirds of patients had de-novo AML. Twenty-four percent of patients did not receive induction chemotherapy and were treated with best supportive care, leaving 130 patients who received induction chemotherapy. Overall median survival for chemotherapy treated patients was 409 days, compared with 44 days for patients treated with best supportive care. The majority of patients (77%) who received chemotherapy were treated with standard induction consisting of 3 days of an anthracycline and 7-10 days of continuous infusion cytarabine. Of the patients treated with induction chemotherapy, 65% received prophylaxis with fluconazole and 32% did not, the remainder received prophylaxis with other antifungal agents. The use of prophylactic fluconazole coincided with implementation of our antifungal policy. Of patients who were treated with fluconazole prophylaxis, 62% required parenteral antifungal therapy and 38% did not. Of patients who did not receive fluconazole prophylaxis 56% required parenteral antifungals and 44% did not. These differences relating to receiving fluconazole prophylaxis were not statistically significantly different. For those patients requiring empiric antifungal therapy, they received a median of 18 days of fluconazole (range 3-156 days). Of the 56 patients who were treated with amphotericin B as empiric therapy, 59% were changed to another agent due to renal effects (42%), fever (27%) or other adverse effects (21%). Switching off amphotericin B occurred after a median of 7.5 days (range 0-59 days). Fifty-six percent of patients received caspofungin as the second line agent while the policy was in effect. Conclusion:Based on our retrospective analysis of the practical use of antifungal prophylaxis within our institutional antifungal policy, fluconazole prophylaxis did not decrease the need for empiric parenteral antifungal therapy. The majority of patients treated with empiric amphotericin B were switched to a second line agent, mostly due to intolerance or adverse effects. Disclosures:No relevant conflicts of interest to declare.

The changing epidemiology of invasive candidiasis

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST). The medical and electronic records of all patients with cancer who had candidemia at the authors' institution from 1993 to 2003 were reviewed for demographic data and clinical information, including the use of prophylactic fluconazole, the infecting Candida species, and the source of candidemia (catheter-related vs other apparent sources). Six hundred thirty-five patients with candidemia were analyzed. C. glabrata and C. krusei were the leading causes of candidemia in 31% and 24% of patients with HM, respectively, and in 18% and 2% of patients with ST, respectively (P < .001). A catheter was the source of candidemia in 36% of the patients with ST and in 12% of the patients with HM (P < .001). Response to antifungal therapy occurred in 73% of the ST group compared with 49% of the HM group (P < .001). Multivariate logistic regression analysis revealed that fluconazole prophylaxis was a risk factor for both C. glabrata and C. krusei candidemia. The analysis also identified neutropenia as a risk factor for all candidemia and catheter-related infection as a risk factor for C. parapsilosis candidemia. The results of this study indicated that C. glabrata and C. krusei were the leading causes of candidemia in patients with HM. Neutropenia was the leading risk factor for all candidemia, whereas the catheter was the leading risk factor for C. parapsilosis candidemia.

Analytical Reviews: Antifungal Therapies in the Intensive Care Unit

Fungal infections are increasing nationwide, paralleling increases in the number of immunosuppressed hosts. Most of the candida infections seen in the intensive care unit are likely due to iatrogenic factors such as hyperalimentation, catheters, broad-spectrum antibiotics, and postprocedure complications that are prevalent in intensive care unit patients. Delays in appropriate therapy are common and may compromise care. Fortunately, the recognition of several clinical syndromes in the intensive care unit that require specialized treatment can improve outcomes. The issue of antifungal prophylaxis has to be balanced against issues of resistance, and current guidelines are reviewed here for prophylactic use of fluconazole only in selected intensive care unit patients. Finally, several new antifungal agents are available to treat the emerging resistant fungi, with better toxic/therapeutic ratios than in the past. Thus, there are an increasing number of safer and more effective options for treating fungal infections in the intensive care unit.

Antifungal drug susceptibility of Cryptococcus neoformans from clinical sources in Nairobi, Kenya

The serotypes and mating types of 80 clinical isolates of Cryptococcus neoformans from Kenya were studied and subjected to broth microdilution susceptibility testing to amphotericin B (AMP), flucytosin, fluconazole (FLC), itraconazole (ITC) and miconazole (MCZ). The isolates included C. neoformans var. grubii- 75 of 80 (serotype A; 93.7%), C. neoformans var. neoformans- three of 80 (3.8%) and C. neoformans var. gattii- two (serotype B; 2.5%). Mating experiment confirmed all the isolates to be alpha-mating type. Seventy-eight (97.5%) of the isolates had minimum inhibitory concentration (MIC) of < or =0.5 microg ml(-1) to AMP and at 1 microg ml(-1), 100% of the isolates were inhibited. Flucytosin resistance was observed in 21% with MIC in which 90% of the isolates were inhibited (MIC90) of 64 microg ml(-1). Only 23.8% of the strains were susceptible to FLC with 65% susceptible dose-dependent (SDD) and 11.2% resistant. Itraconazole susceptibility was 61.3% while the rest were either SDD or resistant. The MIC90 for ITC and MCZ were 0.5 and 2 microg ml(-1) respectively. The study reports the serotypes, mating types and highlights the existence of azoles resistance in C. neoformans in Nairobi which calls for antifungal drug resistance surveillance as prophylactic use of FLC increases because of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in sub-Saharan Africa.

Use of prophylactic fluconazole in a neonatal intensive care unit: efficacy is similar to that described in adult high-risk surgical patients

We read with great interest the recent article by Ho and coworkers [1] concerning the use of prophylactic fluconazole in high-risk surgical patients, in which those authors reported on seven randomized controlled studies from the Cochrane Controlled Trial Register. Ho and colleagues concluded that the use of prophylactic fluconazole in immunocompetent high-risk surgical patients is associated with a reduced incidence of candidaemia, fewer patients requiring systemic amphotericin B as rescue therapy for systemic fungal infection, and no increase in the proportion of patients colonized with or infected with fluconazole-resistant fungi, but with only a trend toward a reduction in hospital mortality. In addition to the high-risk surgical patients considered by Ho and coworkers [1], preterm neonates in the neonatal intensive care unit are at increased risk for fungal colonization and infection but – despite positive reports from a limited number of institutions including ours [2-4] – the use of prophylactic fluconazole in these subsets is not yet viewed as a standard of care [5]. Nevertheless, in our tertiary neonatal intensive care unit we began to use fluconazole in 2001 in all neonates with birth weight less than 1500 g, and our findings are fully consistent with the data reported by Ho and colleagues. In particular, when we analyzed the decade from 1996 to 2005 and compared the period 2001–2005 with the 5-year period before the introduction of fluconazole prophylaxis (388 versus 345 patients, respectively), we found significant reductions in fungal colonization (any site: from 45.2% to 23.9%, 95% confidence interval 0.265–0.608; P < 0.0001), fungal systemic infection (from 16.1% to 4.6%, 95% confidence interval 0.135–0.498; P < 0.0001) and rates of progression from colonization to infection (from 0.36 to 0.18, 95% confidence interval 0.148–0.802; P = 0.01), with no increase in the number of infants colonized (10/345 versus 11/388; P = 0.45) or infected (5/345 versus 4/388; P = 0.35) by fluconazole-resistant fungi. Similarly to the findings reported by Ho and coworkers, overall hospital mortality was not significantly reduced with fluconazole (from 11.8% to 10.4%; P = 0.29); however, colonized infants treated with prophylactic fluconazole were significantly more likely to survive than were those who were not treated (mortality rate 4.1% versus 17.7%, 95% confidence interval 0.039–0.778; P = 0.008). Our data confirm the effectiveness of the strategy of administering prophylactic fluconazole in a population of high-risk patients other than those most frequently described (i.e. high-risk surgical patients), and suggest that extension of this policy to high-risk patients in neonatal intensive care settings is warranted.

Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis

To investigate the relative pathogenicity of Candida albicans treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. Previous studies indicate that these cells secrete 10 times more farnesol than do untreated cells. In our usage, subinhibitory means a concentration which causes a prominent decrease in turbidity but still allows some cell growth. C. albicans A72 cells were grown overnight in 0-5.0 microM fluconazole, washed, and inoculated in mice by tail vein injection. Groups of 15 or 16 mice were injected with 1.3 x 10(6) cells and mortality was recorded for 7 days post-inoculation. The levels of farnesol in control and treated C. albicans were determined by GC/MS. The MIC50 for strain A72 was 0.125 mg/L (0.4 microM). Mice administered C. albicans pre-treated with 0.5 to 1.0 microM fluconazole died 2.5 to 4 days earlier and had 2 to 4 times higher mortality rates than mice given untreated C. albicans. Fluconazole (0.5 to 1.0 microM) pre-treated cells were 4.2 to 8.5 times more lethal (P < 0.001) than untreated cells. The extracellular, membrane bound, and intracellular farnesol concentrations of cells pre-treated with 1.0 muM fluconazole were 12-, 2- and 6-times those of untreated cells. The effects of fluconazole on C. albicans are very concentration-dependent. The enhanced pathogenicity of fluconazole pre-treated C. albicans in mice should be relevant to the therapeutic and prophylactic use of fluconazole. Further research is needed to explore whether farnesol production by C. albicans is a virulence factor.

Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta‐analysis of randomised‐controlled trials

Fluconazole and itraconazole are used as antifungal prophylaxis in neutropenic patients with haematological malignancies. A meta-analysis of randomised-controlled trials (RCTs) was performed in order to compare their safety and effectiveness in this population. Data were obtained from PubMed, Current Contents, Cochrane Central Register for Controlled Trials and references from relevant articles. Five RCTs were included in the analysis. Publication bias and statistically significant heterogeneity was not observed among the analysed studies. Fewer patients were withdrawn due to the development of adverse effects associated with fluconazole when compared with itraconazole [odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.18-0.41]. On the contrary, prophylactic use of fluconazole resulted in significantly more fungal infections (documented and suspected infections combined, OR = 1.62, 95% CI: 1.06-2.48). There were no statistically significant differences regarding documented fungal infections (OR = 1.51, 95% CI: 0.97-2.35), invasive fungal infections (OR = 1.44, 95% CI: 0.96-2.17), overall mortality (OR = 0.89, 95% CI: 0.63-1.24) and mortality attributed by the authors to fungal infections (OR = 1.30, 95% CI: 0.75-2.25) between the two medications. These data suggest that, even though itraconazole is more effective than fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies, the development of more adverse effects may limit its use.

Candida species distribution in bloodstream cultures in Lyon, France, 1998–2001

In order to determine the types of Candida spp. isolated from bloodstream cultures in Lyon, France, a retrospective study of isolates collected at five different bacteriology laboratories from 1998 to 2001 was conducted. During this period Candida spp. were isolated from 190 patients hospitalized in the internal medicine (32%), hematology (23%) and surgery (23%) wards, and in intensive care units (22%). C. albicans was the leading cause of Candida infection (49.5%), followed by C. glabrata (12.6%) and C. parapsilosis (12.1%). Among the onco-hematology patients, the major cause of candidemia was C. krusei (34%), followed by C. albicans (19%), while these two species were identified in 4% and 59% of patients in the other wards, respectively. In the single onco-hematology ward that was specialized in treating acute myeloid leukemia, 14 C. krusei isolates were identified in this study, which contrasts with the single C. krusei isolate recorded between 1992 and 1996. Since C. krusei has inherent resistance to the antifungal agent fluconazole, prophylactic use of fluconazole in these patients was investigated, but no relationship between these two parameters was found.

The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis

IntroductionHigh-risk surgical patients are at increased risk of fungal infections and candidaemia. Evidence from observational and small randomised controlled studies suggests that prophylactic fluconazole may be effective in reducing fungal infection and mortality. We evaluated the effects of prophylactic fluconazole on the incidence of candidaemia and hospital mortality in immunocompetent high-risk surgical patients.MethodsRandomised controlled studies involving the use of fluconazole in immunocompetent high-risk surgical patients from the Cochrane Controlled Trial Register (2005, issue 1) and from the EMBASE and MEDLINE databases (1966–30 April 2005), without any language restriction, were included. Two reviewers reviewed the quality of the studies and performed data extraction independently.ResultsSeven randomised controlled studies with a total of 814 immunocompetent high-risk surgical patients were considered. The use of prophylactic fluconazole was associated with a reduction in the proportion of patients with candidaemia (relative risk [RR] = 0.21, 95% confidence interval [CI] = 0.06–0.72, P = 0.01; I2 = 0%) and fungal infections other than lower urinary tract infection (RR = 0.39, 95% CI = 0.24–0.65, P = 0.0003; I2 = 0%), but was associated with only a trend towards a reduction in hospital mortality (RR = 0.82, 95% CI = 0.62–1.08, P = 0.15; I2 = 7%). The proportion of patients requiring systemic amphotericin B as a rescue therapy for systemic fungal infection was lower after prophylactic use of fluconazole (RR = 0.35, 95% CI = 0.17–0.72, P = 0.004; I2 = 0%). The proportion of patients colonised with or infected with fluconazole-resistant fungi was not significantly different between the fluconazole group and the placebo group (RR = 0.66, 95% CI = 0.22–1.96, P = 0.46; I2 = 0%).ConclusionThe use of prophylactic fluconazole in immunocompetent high-risk surgical patients is associated with a reduced incidence of candidaemia but with only a trend towards a reduction in hospital mortality.