Ninety-three hospitalizations of 70 patients, who underwent induction chemotherapy for acute leukemia to determine the effectiveness of oral nystatin in preventing oropharyngeal and systemic candidiasis were reviewed. Sixty-two percent of patients who received prophylactic nystatin and 58% of patients who did not receive nystatin developed oropharyngeal candidiasis; 11% of patients who received prophylaxis and 21% of those who did not receive prophylaxis developed systemic candidiasis. The use of oral nystatin did not significantly diminish the risk of developing either type of Candida infection. Oropharyngeal candidiasis occurred more commonly in patients who had severe and prolonged leukopenia, had received more parenteral antibiotics, and had developed chemotherapy-induced mucositis. Systemic candidiasis developed almost exclusively in patients who had prior oropharyngeal candidiasis. Guidelines for the empiric use of amphotericin B in these patients are provided.

The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.

113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.

Polyene antibiotics such as nystatin and amphotericin B are among the most widely recommended drugs for use against oral candidiasis. It is also generally accepted that chlorhexidine gluconate is an appropriate adjunct or an alternative to specific antimycotic drugs. The aim of the present study was to examine the effect of the combination of nystatin and chlorhexidine digluconate on Candida albicans in vitro. The minimum inhibitory concentration (MIC) value for the combination of the two drugs was found to be significantly higher than the values for each of the drugs alone, approximately 33 times the MIC value for the nystatin solution and 4 times the value for chlorhexidine digluconate. The results of the MIC study and the presence of a precipitate in all combinations of nystatin and chlorhexidine digluconate showed that the combination of the drugs is not effective in vitro against Candida albicans. The most likely reason is that a low solubility chlorhexidine-nystatin salt is formed, thus rendering the combined drug complex ineffective as an antibiotic agent.

The efficacy and safety of itraconazole oral solution and a combination of amphotericin B capsules plus nystatin oral suspension were compared in the prophylaxis of fungal infections in neutropenic patients. In an open, randomized, multicentre trial, 144 patients received itraconazole oral solution 100 mg bd, and 133 patients received amphotericin B 500 mg tds plus nystatin 2 MU qds. Overall, 65% of itraconazole-treated patients were considered to have had successful prophylaxis, compared with 53% in the polyene group. Proven deep fungal infections occurred in 5% of patients in each group. Fewer patients receiving itraconazole than amphotericin plus nystatin had superficial infections (3 versus 8%; P = 0.066). This trend in favour of itraconazole was seen in patients with profound neutropenia (neutrophil count <0.1 x 10(9) cells/L at least once) or prolonged neutropenia (neutrophil count <1.0 x 10(9) cells/L for >14 days). The median time to prophylactic failure was longer in the itraconazole group (37 days) than in the polyene group (34 days). The number of patients with fungal colonization (nose, sputum, stool) changed more favourably from baseline to endpoint in the itraconazole group than in the polyene group. Both treatments were safe and well tolerated; however, patients receiving amphotericin plus nystatin had a higher incidence of nausea and rash. In conclusion, itraconazole oral solution at doses of 100 mg bd and oral amphotericin B plus nystatin have similar prophylactic efficacy against fungal infections in neutropenic patients. On the basis of reduced incidence of superficial fungal infections, fungal colonization and specific adverse events, itraconazole may be the preferred treatment.

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.

The authors reviewed the charts of 26 recipients of a left ventricular assist device to determine the incidence of fungal infections and the clinical course of these patients. Nine patients (35%) had positive fungal cultures. Of these, six had clinical infections and three were colonized asymptomatically. Three of the six infected patients (including one with mediastinal sepsis and another requiring left ventricular assist device replacement for intractable fungemia) underwent orthotopic heart transplantation after successful therapy. Of the remaining three, one died of a thromboembolic stroke (probably septic in nature), one died secondary to driveline rupture, and the third succumbed to culture-negative sepsis. Two of the colonized patients underwent transplantation, and the third succumbed to perioperative right sided circulatory failure and hypoxia. Positive fungal cultures were a common finding in our series. Because of a significant incidence of fungal infection-related morbidity, the authors revised their pre operative and post operative protocol to include: 1) 2 weeks of fluconazole therapy (200 mg intravenously daily) for patients receiving broad spectrum antibiotics and for those with evidence of preoperative fungal colonization; 2) daily dressing changes around drivelines; 3) daily nystatin swish and swallow; and 4) empiric fluconazole treatment for culture-negative sepsis. Using this protocol, three left ventricular assist device recipients received prophylactic fluconazole and had no evidence of fungal morbidity or mortality on short-term follow-up.

Denture biofilms represent a protective reservoir for oral microbes. The study of the biology of Candida in these biofilms requires a reliable model. A reproducible model of C. albicans denture biofilm was developed and used to determine the susceptibility of two clinically relevant C. albicans isolates against 4 antifungals. C. albicans, growing as a biofilm, exhibited resistance to amphotericin B, nystatin, chlorhexidine, and fluconazole, with 50% reduction in metabolic activity (50% RMA) at concentrations of 8, 16, 128, and > 64 microg/mL, respectively. In contrast, planktonically cultured C. albicans were susceptible (50% RMA for the same antifungals was obtained at 0.25, 1.0, 4.0, and 0.5 microg/mL, respectively). In conclusion, results obtained by means of our biofilm model show that biofilm-associated C. albicans cells, compared with cells grown in planktonic form, are resistant to antifungals used to treat denture stomatitis.

Patients with cancer and infectious diseases often have changes in the composition and concentration of their different blood components. These changes include variations in the composition and concentration of plasma lipoprotein lipids, in transfer rates of endogenous lipid between different lipoprotein classes, and in concentrations of phagocytic cells (i.e., monocytes and macrophages). It appears that the interaction of many lipid-based drug formulations with plasma lipoproteins and blood phagocytic cells may be responsible for the unpredictable pharmacokinetics and pharmacodynamics of those compounds when administered to patients with diseases. This review examines the potential mechanisms that may explain the biological behavior of lipid-based drug formulations used in the treatment of infectious diseases and cancer.

Candidal adherence to denture acrylic surfaces is implicated as the first step in the pathogenesis of Candida-associated denture stomatitis, the most prevalent form of oral candidosis in the West. This condition is treated by topically administered antifungal agents, mainly belonging to the polyenes and azoles. As the intraoral concentrations of antifungals fluctuate considerably due to the dynamics of the oral environment, the effect of short exposure to sublethal concentrations of antifungals on the adhesion of Candida albicans to denture acrylic surfaces was investigated. Seven oral C. albicans isolates were exposed to four-eight times minimum inhibitory concentrations (MIC) of five antifungal drugs, nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole, for 1 h. After removing the drug (by repeated washing) the adhesion of these isolates to acrylic strips was assessed by an in vitro adhesion assay. Exposure to antifungal agents significantly reduced the adherence of all seven C. albicans isolates to denture acrylic. The mean percentage reductions of adhesion after limited exposure to nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole were 86.48, 90.85, 66.72, 65.88 and 47.42%, respectively. These findings indicate that subtherapeutic doses of antifungals may modulate oral candidal colonization. Further, these results may have an important bearing on dosage regimens currently employed in treating oral candidosis.