Ketoconazole and candidiasis: a controlled study. Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study. Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. Prophylaxis of candidiasis in cancer patients. Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse. An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis. Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer. Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer. Once-weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS-related complex: a double-blind placebo-controlled study. Gentian violet, ketoconazole and nystatin in oropharyngeal and esophageal candidiasis in Zairian AIDS patients. Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis. A randomized trial comparing ketoconazole and nystatin prophylactic therapy in neutropenic patients. Fluconazole once a week as secondary prophylaxis against oropharyngeal candidiasis in HIV-infected patients. A double-blind placebo-controlled study. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Fluconazole versus ketoconazole in the treatment of oropharyngeal candidiasis in HIV-infected children. Multicentre Study Group. Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials. Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection. Effect of chlorhexidine rinsing on the oropharyngeal ecology in patients with head and neck cancer who have irradiation mucositis. A comparative study of the efficacy of fluconazole and amphotericin B in the treatment of oropharyngeal candidosis in patients undergoing radiotherapy for head and neck tumours. Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. Selective decontamination of the digestive tract to prevent postoperative infection: a randomized placebo-controlled trial in liver transplant patients. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS.
A double-blind, placebo-controlled study was undertaken to determine the efficacy of ketoconazole in the treatment of candidiasis. The drug was administered orally in the dosage of 200 mg/m2 of body surface per day for two weeks to cancer patients with oral candidiasis. Randomization in a 2:1 ratio provided 36 patients treated with ketoconazole and 20 managed with a placebo. Regression of visible lesions was achieved in 26 (72%) of 36 ketoconazole-treated and four (20%) of 20 untreated patients; eradication of culturable organisms occurred in 12 (36%) of 33 ketoconazole-treated and one (7%) of 14 untreated patients; and resolution of lesions plus eradication of Candida albicans occurred in nine (25%) of 36 ketoconazole-treated and one (5%) of 20 untreated patients. Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired. A prospective, randomized, controlled, double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer. Fifty-six patients receiving induction chemotherapy for acute leukemia, autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms, multidrug chemotherapy for malignant lymphoma, or corticosteroids for brain metastases were randomized to receive either oral ketoconazole, 400 mg/d, or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped. Oral candidiasis developed in eight (28%) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole. However, ketoconazole failed to prevent Candida esophagitis and vulvovaginitis in two patients and one patient, respectively. Furthermore, prophylactic use of ketoconazole did not significantly alter the total number of hospital days, febrile days, or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant. Since oral candidiasis can be successfully managed by several different treatment modalities when it does occur, we do not think that the routine prophylactic use of ketoconazole is justified. Optimal therapy for oropharyngeal candidiasis, a common infection in immunocompromised patients, has yet to be clearly defined. Topical therapy is usually poorly tolerated; ketoconazole is effective but absorption is highly variable. New antifungal agents have been developed to increase the therapeutic options. Fluconazole is active against yeasts, is available in both oral and intravenous formulations, and has a pharmacokinetic profile different from that of ketoconazole. This randomized double-blind study evaluates systemic antifungal therapy with fluconazole (100 mg daily) or ketoconazole (400-mg daily) for oropharyngeal candidiasis in patients with cancer. Clinical cure was observed in 15 of 19 and 14 of 18 patients treated with fluconazole and ketoconazole, respectively. Eradication of pathogenic yeasts ws documented for 10 patients in both groups. The rates of relapse were similar, but relapse occurred earlier in patients in the ketoconazole group. Overall, this study demonstrates the value of a dosage of 100 mg of fluconazole or of 400 mg of ketoconazole daily for the management of oropharyngeal candidiasis in patients with cancer. 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. 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. Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole. An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer. The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biotène Oral Balance gel [Lacléde Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biotène products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biotène products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer. Fluconazole 50 mg daily for 14-28 days was effective in the treatment of patients with AIDS and AIDS-related complex with severe oropharyngeal and oesophageal candidiasis. Of 24 patients entered, 17 (81%), including seven with oesophageal candidiasis, were clinically cured and two (9.5%) improved at the end of treatment. Following clinical cure, 14 patients were entered into the double-blind phase of the study, where fluconazole (150 mg) or placebo capsules were given once weekly. Treatment was double blind. Fluconazole 150 mg once weekly was found to be effective in maintaining patients both clinically and mycologically free of oropharyngeal candidiasis. A randomized un-blinded study on the treatment of oropharyngeal and esophageal candidiasis was conducted in Kinshasa (Zaire), among 141 inpatients with AIDS and oropharyngeal candidiasis, of whom 136 also had esophageal candidiasis. The study compared the efficacy of gentian violet mouth washes (1.5 ml 0.5% aqueous solution b.i.d.), oral ketoconazole (200 mg/day, after a meal) and nystatin mouth washes (200.000 U oral suspension q.i.d.). Patients treated with mouth washes swallowed their medication after mouth washing. Patients enrolled in this study had a very high mortality (probability of death: 41.6% after 14 days). After 14 days, 72 patients could be evaluated. At that time, oropharyngeal lesions had disappeared in similar proportions of patients treated with gentian violet (11/26, 42%) and ketoconazole (10/23, 43%), and in a lower proportion of patients treated with nystatin (2/23, 9%; p less than 0.05). In esophageal candidiasis, ketoconazole seemed more efficient than both other treatments: esophageal lesions had disappeared in 5 (24%) of the 21 patients on ketoconazole, compared to less than 10% of patients on both other treatments (p = 0.07). The suboptimal results observed with all 3 treatments could be explained by the profound immunosuppression of patients enrolled in the study. This study suggests that gentian violet is effective treatment for oropharyngeal candidiasis. As it is very cheap (0.5 US$/treatment course in Kinshasa), we suggest that its use should be assessed in larger studies. In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intraarterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n = 7) was given G-CSF and group B (n = 7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (< 2,000/mm3). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3: group A-1 (n = 3) and group A-2 (n = 4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis. 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. To assess the efficacy and tolerance of fluconazole (150 mg oral dose, once a week) in the prevention of recurrent oropharyngeal candidiasis in patients with moderate to severe human immunodeficiency virus (HIV) infection.
                A randomised, double-blind, placebo-controlled trial.
                Eighty-four patients with moderate to severe HIV infection who had successfully completed two to four weeks treatment with fluconazole for oropharyngeal candidiasis were randomly allocated to receive either placebo or fluconazole. Pre-treatment clinical and laboratory characteristics were similar in the two groups.
                Success was classified as absence throughout the course of treatment of clinical evidence of oropharyngeal candidiasis, and failure as recurrence or relapse of symptomatic oropharyngeal candidiasis.
                Of 73 evaluable patients the median time to relapse was > or = 168 days in the fluconazole group and 37 days in the placebo group (P < 0.0001). One patient in the placebo group and 18 patients in the fluconazole group completed six months' treatment without clinical relapse (P < 0.001).
                Fluconazole was well tolerated and prevented clinical relapse of oropharyngeal candidiasis in 71% of patients who completed three months of treatment (95% confidence interval [CI], 55-86) and 58% (95% CI, 41-75) who completed six months of treatment. To evaluate the efficacy and safety of intravenous fluconazole for the prevention of intra-abdominal Candida infections in high-risk surgical patients.
                Randomized, prospective, double-blind, placebo-controlled study.
                Two university-affiliated hospitals in Switzerland.
                Forty-nine surgical patients with recurrent gastrointestinal perforations or anastomotic leakages.
                Prophylaxis with intravenous fluconazole (400 mg per day) or placebo continued until resolution of the underlying surgical condition.
                Patients were evaluated daily, and specimens for culture were obtained three times per week during prophylaxis. The primary study end points were the frequency of and the time to intra-abdominal Candida infections. Secondary end points were the frequency of candidiasis (intra-abdominal and extra-abdominal) and the emergence or persistence of Candida colonization. Among patients who were not colonized at study entry, Candida was isolated from surveillance cultures during prophylaxis in 15% of the patients in the fluconazole group and in 62% of the patients in the placebo group (relative risk, 0.25; 95% confidence interval, 0.07 to 0.96; p = .04). Candida peritonitis occurred in one of 23 patients (4%) who received fluconazole and in seven of 20 patients (35%) who received placebo (relative risk, 0.12; 95% confidence interval, 0.02 to 0.93; p = .02). In addition, one catheter-related Candida albicans sepsis occurred in a fluconazole-treated patient. Thus, overall, candidiasis developed in two fluconazole patients and seven placebo patients (relative risk, 0.25; 95% confidence interval, 0.06 to 1.06; p = .06). C. albicans accounted for 87% of the Candida species isolated before or during prophylaxis, and all C. albicans strains were susceptible to fluconazole. Fluconazole was well tolerated, and adverse events occurred at similar frequencies in both treatment groups.
                Fluconazole prophylaxis prevents colonization and invasive intra-abdominal Candida infections in high-risk surgical patients. In an open multicentre study the efficacy and safety of fluconazole versus ketoconazole were evaluated in the treatment of 46 pediatric patients with oropharyngeal candidiasis and AIDS or HIV infection. Twenty-four subjects received oral fluconazole in a dosage of 3 mg/kg/day and 22 subjects received oral ketoconazole in a dosage of 7 mg/kg/day. The treatment duration ranged from 5 to 49 days. Results showed that fluconazole and ketoconazole have comparable efficacy and safety in the treatment of oropharyngeal candidiasis in HIV-infected children. Patients treated with fluconazole had higher clinical and mycological cure rates at the end of therapy (88% and 71% respectively) than those treated with ketoconazole (81% and 57% respectively). One case of drug-related side effects (diarrhea and abdominal pain) in a patient receiving ketoconazole resulted in discontinuation of treatment. Follow-up examinations 2 and 4 weeks post-treatment showed a comparably high rate of relapse in both patient groups. Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year.
                This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer.
                The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P =.04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P <.001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex.
                Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer. To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children.
                Multicenter, randomized, observer-masked trial.
                Thirty-two centers participated, including hospitals and ambulatory care clinics.
                We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety.
                Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug.
                Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated. To evaluate the efficacy of pure natural honey as prophylaxis against radiochemotherapy-induced mucositis, through clinical scoring of oral and oropharyngeal mucositis, and culturing of pathogenic oral and oropharyngeal microbes.
                The study was done in Assiut University Hospital, Egypt, between January 2005 and July 2006. Forty patients diagnosed with head and neck cancer were entered into the trial. Enrolled patients were randomised to either the treatment group, receiving concomitant chemotherapy and radiotherapy (with a significant area of directly visible oral and/or oropharyngeal mucosa included in the radiation fields) plus prior topical application of pure natural honey, or the control group, receiving concomitant chemotherapy and radiotherapy without honey. Patients were evaluated clinically every week to assess development of radiation mucositis. Aerobic cultures and candida colonisation assessment were undertaken, via oral and oropharyngeal swabs, prior to and at the completion of irradiation, and when infection was evident.
                In the treatment group, no patients developed grade four mucositis and only three patients (15 per cent) developed grade three mucositis. In the control group, 13 patients (65 per cent) developed grade three or four mucositis (p < 0.05). Candida colonisation was found in 15 per cent of the treatment group and 60 per cent of the control group, either during or after radiotherapy (p = 0.003). Positive cultures for aerobic pathogenic bacteria were observed in 15 per cent of the treatment group and 65 per cent of the control group, during or after radiotherapy (p = 0.007).
                This study shows that prophylactic use of pure natural honey was effective in reducing mucositis resulting from radiochemotherapy in patients with head and neck cancer. To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis.
                A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed.
                The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034).
                Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings. Oral flora is thought to contribute to irradiation mucositis in patients with head and neck cancer. Neglect of oral hygienic care may also contribute to mucositis. The purpose of this prospective, randomized, placebo-controlled, double-blind study was to evaluate the effect of chlorhexidine 0.1% mouthrinses on oral flora and irradiation mucositis. This study included 30 patients with head and neck cancer who had comparable irradiation portals. One group (N = 15) rinsed four times daily with chlorhexidine 0.1%, the other group (N = 15) with a placebo. The oral flora was cultured (oral washing technique) twice before and three times per week during the period of radiotherapy. On the same days, the severity of mucositis was determined. The colonization index of viridans streptococci was significantly reduced only after 5 weeks of chlorhexidine 0.1% treatment. The colonization patterns of Candida species, Streptococcus faecalis, staphylococci, and Enterobacteriaceae, Pseudomonadaceae, and Acinetobacter species were not influenced by 5 weeks of use of chlorhexidine rinses when compared with the placebo. No differences were seen between the two study groups in the development and severity of mucositis. In conclusion, suppression of oral flora and a lowering of the severity of mucositis by means of disinfecting mouthrinses were not successful. Radiotherapy given during treatment of oral and pharyngeal malignancy is frequently associated with colonization of the oral mucosa by Candida species. Treatment of these infections has included topical and systemic agents. In the present study 73 patients with oropharyngeal candidosis were treated with either amphotericin B (10 mg lozenges, four times daily for 14 days, 36 patients) or fluconazole (50 mg daily for 7 days, 37 patients). The yeasts most frequently isolated were C albicans and C glabrata. Clinical signs and symptoms showed improvement at end of treatment in 72% of patients who received amphotericin B compared with 92% of patients who received fluconazole. Mycological cure at end of treatment was achieved in 31% of the amphotericin B group and 46% of patients who received fluconazole. For both treatments the cure rate was less in denture wearers than in non denture wearers. Infections caused by Candida spp. are a major cause of morbidity and mortality in critically ill patients and usually develop from endogenous colonization. We assessed the effectiveness of adding fluconazole to a selective digestive decontamination regimen to prevent candidal infections.
                We performed a prospective, randomized, double-blind, placebo-controlled trial among medical and surgical intensive care unit patients at a large university hospital.
                All adult patients mechanically ventilated for at least 48 h with an expectation to remain so for at least an additional 72 h, and receiving selective decontamination of the digestive tract.
                Patients were randomly assigned fluconazole 100 mg daily (n=103) or placebo (n=101).
                Candida infections occurred less frequently in the fluconazole group (5.8%) than in the placebo group (16%; rate ratio 0.35; Cl(95) 0.11-0.94). Some 90% of candidemia episodes occurred in the placebo group (rate ratio for fluconazole use 0.10; Cl(95) 0.02-0.74). The rate of treatment failure, development of candidal infection, or increased colonization, was 32% in the fluconazole group and 67% in the placebo group (P<0.001). Crude in-hospital mortality was similar in the two groups (39% fluconazole vs. 41% placebo).
                Prophylactic use of fluconazole in a selected group of mechanically ventilated patients at high risk for infection reduces the incidence of Candida infections, in particular candidemia. 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 determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver.
                Randomized, double-blind, placebo-controlled study.
                Two academic teaching hospitals.
                Adult patients undergoing elective liver transplantation: 26 patients receiving SDD and 29 patients receiving a placebo.
                Patients undergoing SDD were administered 400 mg of norfloxacin once daily as soon as they were accepted for transplantation. Postoperative treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and 10 mg of amphotericin B, four times daily, combined with an oral paste containing a 2% solution of the same drugs until postoperative day 30. Prophylactic intravenous administration of antibiotics was not part of the SDD regimen in this study. Control patients were given a similar regimen with placebo drugs.
                The mean number of postoperative bacterial and fungal infections in the first 30 days after transplantation was the primary efficacy end point. Days on a ventilator, days spent in the intensive care unit, and medical costs were registered as secondary outcome variables.
                Of the 26 patients undergoing SDD, 22 (84.5%) developed an infection in the postoperative study period; in the placebo group (n = 29), these numbers were not significantly different (25 patients, 86%). The mean number of postoperative infectious episodes per patient was also not significantly different: 1.77 (SDD) vs. 1.93 (placebo). Infections involving Gram-negative aerobic bacteria and Candida species were significantly less frequent in patients receiving SDD (p <.001 and p <.05). Total costs were higher in the group receiving SDD.
                Selective decontamination of the digestive tract does not prevent infection in patients undergoing elective liver transplantation and increases the cost of their care. It does, however, affect the type of infection. Infections with Gram-negative bacilli and with Candida species are replaced by infections with Gram-positive cocci. In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). 20 episodes (18 patients) were treated with fluconazole and 20 episodes (19 patients) with ketoconazole. Pretreatment clinical features and laboratory test results were similar in both groups. 17 episodes (85%) in the fluconazole group and 16 (80%) in the ketoconazole group could be evaluated. There was clinical cure at the end of therapy in all fluconazole-treated and 12 of 16 (75%) ketoconazole-treated episodes. Cultures were negative at the end of therapy in 87% of the fluconazole group and 69% of the ketoconazole group. 1 patients stopped taking fluconazole because of severe nausea. 1 of 18 fluconazole-treated and 4 of 19 ketoconazole-treated patients had transient rises in alanine or aspartate aminotransferase. Fluconazole seemed more effective than ketoconazole in the treatment of oral thrush among AIDS and ARC patients.
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.