Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ketoconazole prophylaxis in patients with solid tumours receiving aggressive immunosuppressive therapy. An open randomized comparison between 200 mg/d and 400 mg/d doses. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight. Infection prophylaxis in acute leukemia. Comparative effectiveness of sulfamethoxazole and trimethoprim, ketoconazole, and a combination of the two. Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. Prevention and therapy of fungal infection in severe acute pancreatitis: A prospective clinical study.
Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.
                Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.
                Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).
                At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia. To evaluate the prophylactic use of enteral fluconazole to prevent invasive candidal infections in critically ill surgical patients.
                Invasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant patients, few studies have focused on surgical patients and prevention of fungal infection.
                The authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU). A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral fluconazole 400 mg or placebo per day during their stay in the surgical ICU at Johns Hopkins Hospital.
                The primary end point was the time to occurrence of fungal infection during the surgical ICU stay, with planned secondary analysis of patients "on-therapy" and alternate definitions of fungal infections. In a time-to-event analysis, the risk of candidal infection in patients receiving fluconazole was significantly less than the risk in patients receiving placebo. After adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed between patients receiving fluconazole and those receiving placebo.
                Enteral fluconazole safely and effectively decreased the incidence of fungal infections in high-risk, critically ill surgical patients. Forty-three patients, most with solid tumours, were included in a study comparing the antifungal prophylactic effect of ketoconazole (Nizoral; Janssen) 200 mg/d and 400 mg/d during the period of immunosuppressive therapy. Seven patients were not seen for follow-up and 6 died of their underlying disease without clinical evidence of mycosis. Twelve of the patients who could be evaluated received ketoconazole 200 mg/d and 18 received 400 mg/d. No infections occurred during the period of prophylactic treatment. In the group receiving 200 mg/d 10 of 36 cultures (28%) were positive for Candida albicans before prophylaxis. During prophylaxis 5 of 18 cultures (28%) were positive and at the end of the prophylactic regimen 1 out of 37 cultures (3%) was positive. In the 400 mg/d group, 13 of 47 cultures (28%) were positive at the start, 2 out of 20 (10%) were positive during prophylaxis and 1 out of 45 (2%) was still positive at the end. The drug was clinically well tolerated. Twenty of the 30 evaluable patients had no significant biochemical abnormalities, 5 had an increased serum transaminase level, 2 had an increased alkaline phosphatase level, and 3 had combined increases of serum transaminase and alkaline phosphatase levels. These abnormalities are regularly seen in patients with metastatic malignant disease, and are not necessarily related to the ketoconazole prophylaxis. To evaluate the efficacy and safety of fluconazole for prevention of fungal infections.
                A randomized, placebo-controlled, double-blind, multicenter trial.
                Adults (257) undergoing chemotherapy for acute leukemia.
                Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity.
                Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality.
                Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups.
                Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths. We tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants.
                We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients.
                Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented.
                Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance. In a comparative study of infection prophylaxis, patients with acute leukemia receiving remission induction therapy were assigned either no prophylaxis, sulfamethoxazole and trimethoprim, ketoconazole, or the combination of sulfamethoxazole and trimethoprim and ketoconazole. Both sulfamethoxazole and trimethoprim and the combination of sulfamethoxazole and trimethoprim and ketoconazole substantially reduced the overall incidence of infection consequent to a marked decrease in bacterial infection. However, sulfamethoxazole and trimethoprim were associated with an increased rate of fungal infection, while ketoconazole decreased this complication. No form of prophylaxis reduced infectious mortality or increased the complete remission rate. However, because of its effect in reducing infectious morbidity, we conclude that patients with acute leukemia receiving remission induction treatment should be given antibacterial and antifungal prophylaxis. The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 I.U. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5%; confidence interval 2%-23%) on fluconazole and 17 of 48 patients (35.4%; confidence interval 22%-52%) (p < 0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1%) and 11 (22.9%) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8%) and 9 of 48 patients (18.8%) respectively (p < 0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p < 0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease. Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count > 0.5 x 10(9)/L, toxicity precluding further fluconazole use, and death. By Kaplan-Meier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01). To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP).
                Seventy patients with SAP admitted from Jan. 1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were compared.
                The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16% vs 30%, P<0.05 and 9% vs 30%, P<0.01, respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole group.
                Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with SAP. But once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective.
Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one half and total mortality by one quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.