A randomized trial comparing ketoconazole and nystatin prophylactic therapy in neutropenic patients. Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse. Prevention of mycosis in granulocytopenic patients with prophylactic ketoconazole treatment. Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome. Prophylaxis of oropharyngeal candidiasis with clotrimazole. Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study. Prophylaxis of candidiasis in cancer patients. Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients. Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study. Effects of chlorhexidine mouthrinse on oral health in patients with acute leukemia. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Clotrimazole treatment for prevention of oral candidiasis in patients with acute leukemia undergoing chemotherapy. Results of a double-blind study. 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 versus itraconazole for the prevention of fungal infections in haemato-oncology. Oral anticandidal prophylaxis in patients undergoing chemotherapy for acut- leukemia. Prophylaxis of oral candidiasis with clotrimazole troches. Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation. A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Prevention of bacterial and fungal infections in acute leukemia patients: a new and potent combination of oral norfloxacin and amphotericin B. Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group. Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias. Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Antifungal chemoprophylaxis in cancer children: a prospective randomized controlled study. A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto.
A randomized trial was conducted comparing ketoconazole and nystatin in the prevention of oral candidiasis and appearance of invasive fungal infections in 51 neutropenic leukemic patients undergoing induction chemotherapy. Ketoconazole was administered in a 200 mg dose twice daily. Nystatin oral suspension was given in doses of 500,000 units four times daily. Surveillance cultures of the throat and urine were obtained prior to treatment and conducted weekly. Patients were enrolled in the study if the absolute granulocyte count was less than 1500/microliter, if physical examination revealed no evidence of oral candidiasis, no evidence of urinary tract infection, and there was no pulmonary infiltrate on chest x-ray. Patients were continued on study until the absolute granulocyte count reached 1500/microliter, evidence of oral candidiasis appeared, or presumed or proven invasive fungal infections appeared. Of the 46 evaluable patients, 22 received ketoconazole, 3 (14%) developed oral candidiasis, and 5 developed suspected systemic fungal infections (23%). Of 24 patients who received nystatin, 4 (17%) developed oral candidiasis and 8 (33%) developed systemic fungal infections, 4 proven and 4 suspected. Significantly more patients on the nystatin arm progressed to invasive fungal infections. Ketoconazole was not superior to nystatin in reducing the frequency of oral candidiasis but possibly reduced the frequency of invasive fungal infections. Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation. nan Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls. Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls. However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization. Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S). Differences in the clinical course of colonized and non-colonized patients were observed. Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05). Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01). Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02). We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection. Nystatin altered colonization patterns but did not prevent disseminated fungal infection. A total of 202 evaluable cancer patients were randomly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization. Oropharyngeal candidiasis occurred in 1% of the former patients and 27% of the latter patients (P less than .00001). Candida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis. Oropharyngeal candidiasis subsequently developed in 2% of the former patients and 38% of the latter patients (P = less than .00001). Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients. The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS). Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated. 72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients. In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis. The effects of chlorhexidine mouthrinses, used as a supplement to mechanical oral hygiene measures, were studied in patients receiving treatment for acute leukemia. Twenty-eight patients were randomly divided into two groups. During two periods, when the patients were taking medication for the leukemia, one group rinsed with a 0.2% chlorhexidine solution twice daily and the other group did not. Chlorhexidine had no effects of any clinical significance on parameters such as number of days with fever, number of oral lesions, plaque score, gingival bleeding score, or occurrence of candidiasis. There was, however, an increased number of patients who had a burning sensation in the mouth, and a tendency toward increased numbers of salivary enterococci, enterobacteria, and/or Pseudomonas in patients who rinsed with chlorhexidine. The results of the present study do not support the use of chlorhexidine mouthrinses in patients who are able to maintain good oral hygiene by mechanical means during their illness. 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. Fungal infections have become an increasing cause of morbidity in patients with acute leukemia undergoing chemotherapy. Oral candidiasis is prone to develop in these patients, and there is also a risk of the development of esophageal Candida infection. Clotrimazole troches have been previously reported to be effective in the treatment of documented oral Candida infection. This report documents a double-blind controlled study in 30 patients with acute leukemia in which the effectiveness of clotrimazole troches in preventing oropharyngeal candidiasis was assessed. Patients were randomly assigned to receive 10 mg troches of clotrimazole or a placebo three times per day. Mucosal scrapings were obtained weekly and examined directly by smear and culture. There were 28 evaluable patients. Of 12 patients with oral Candida infection, 11 were taking placebo and one received clotrimazole (p = 0.0002). Clotrimazole is effective in preventing oropharyngeal candidiasis. 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 compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies.
                213 consecutive, afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies.
                A randomised, double blind, single centre study. Patients were randomly assigned to receive fluconazole 50 mg or itraconazole 100 mg, both twice daily in identical capsules. An intention to treat analysis was performed on 202 patients, 101 in each group.
                Microbiologically documented systemic fungal infections occurred in four patients in each group. Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole. In all 202 patients, 29 proceeded to intravenous amphotericin (amphotericin B), 16 in the fluconazole group and 13 in the itraconazole group. Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group. All these infections were oral. No major differences were noted in the isolates of fungi in mouth washes and fecal samples. Overall mortality was 8.9% (18 deaths; seven in the fluconazole group, 11 in the itraconazole group). Mortality from microbiologically and clinically documented fungal infection was 4.5% (nine deaths; three in the fluconazole group, six in the itraconazole group). Median time to suspected or proven fungal infection was 16 days in both groups. None of these comparisons reached statistical significance (p < 0.05). No major clinical toxicity was noted and compliance was excellent.
                In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation, fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease. Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals. Fifty-six untreated patients with acute leukemia (38 acute myelogenous leukemia, 16 acute lymphoblastic leukemia, and 2 blast crisis of chronic granulocytic leukemia) were randomized on admission to one of three groups--one to receive oral anticandidal prophylaxis through the period of remission induction chemotherapy with nystatin, another to receive natamycin, and the third to receive no anticandidal prophylaxis. Neither of the first two groups show any advantage over the last and it is concluded that provided gut sterilization regimes are not employed, prophylactic oral anticandidal treatment is of no value in these patients and should be reserved until there is clinical evidence of infection. Oropharyngeal candidiasis is frequently a complication of patients with altered immune states. Clotrimazole troches are effective in the treatment of Candida and were evaluated in this study in a prophylaxis regimen. Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were randomized to receive either clotrimazole (10 mg) or placebo troches three times a day in a prospective, double-blinded study. Eighty-four patients were randomized into the study, 18 patients with leukemia, 19 patients with malignant neoplasms, and 47 patients with renal transplants. Among all patients, thrush developed in 57% while receiving placebo compared with 13% while receiving clotrimazole prophylaxis. Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms, but not for the leukemic patients. Clotrimazole troches are effective in preventing oral candidiasis in a select group of patients. The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers. The current randomized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine, nystatin, and saline solution rinses to reduce the findings of oral mucositis, gingivitis, and oral infection. The results of this study did not show a reduction in mucositis with the use of these rinses. However, potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse. To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B. The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P < 0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy. An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia. We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts. To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.
                A randomized, controlled, multicenter trial.
                30 hematologic units in tertiary care or university hospitals.
                820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.
                Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.
                An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.
                Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).
                Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated. We report a prospective, randomized, controlled study of antifungal chemoprophylaxis in forty immunocompromised children with hematologic malignancies, receiving respectively itraconazole, ketoconazole, amphotericin-B and no prophylaxis. Fungal isolates from patients' saliva or stools were obtained from 19/40 patients (Candida albicans from 15 patients). Disseminated infection was never observed. Fungal isolates were significantly less frequent in the ketoconazole group of patients vs any other group. Systemic antifungal chemoprophylaxis with ketoconazole appears more effective even than the recently introduced itraconazole. In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole. To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections, a randomized, placebo-controlled, double-blind, multicenter trial was conducted: 405 neutropenic patients with hematologic malignancies were randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201 patients), or placebo (204 patients). Proven and suspected deep fungal infection occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole recipients and in 4% of placebo recipients, a difference of 3.5 percentage points (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the itraconazole recipients compared with 4 placebo recipients, a difference of 2 percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was documented in four itraconazole recipients (one death) and one placebo recipient (one death). Side effects causing drug interruption occurred in 18% of itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to Candida species.
There is strong evidence, from randomised controlled trials, that drugs absorbed or partially absorbed from the GI tract prevent oral candidiasis in patients receiving treatment for cancer. There is also evidence that these drugs are significantly better at preventing oral candidiasis than drugs not absorbed from the GI tract.