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.

Reverse isolation and prophylactic oral nonabsorbable antibiotics were evaluated among 64 consecutive noninfected adults with acute nonlymphocytic leukemia admitted for remission induction. Patients were randomly allocated to laminar air flow room reverse isolation with oral nonabsorbable antibiotics (LAF plus A), routine hospital ward care with antibiotics (W plus A), or ward care alone (W). The LAF plus A patients had a significantly decreased incidence of total infection, bacteremias, pneumonias, rectal abscesses, urinary tract infection, and pharyngitis. Infectious deaths were reduced in the LAF plus A group and the time to the first infection or to fatal infection was delayed. The W plus A patients who regularly ingested the antibiotics had a reduction in infections similar to that of the LAF plus A patients but those who could not tolerate the antibiotics had an incidence of infection comparable to the ward patients. The LAF plus A and the W plus A patients also had higher complete remission rates and longer median survival than the unprotected ward patients.

Invasive candidiasis is a feared infection with mortality similar to that of septic shock (40-60%). Improved knowledge of its pathophysiology and the availability of new compounds for antifungal therapy and prophylaxis have contributed to improving the prognosis of severe candidal infections among immunosuppressed patients at the possible cost of the emergence of non-albicans strains of candida with lower susceptibility to azoles. This review focuses on the management of invasive deep-seated candidiasis in critically ill, non-immunocompromised patients. We discuss antifungal use, indications, potential benefit, and main secondary effects. Prevention strategies include pre-emptive antifungal therapy and azole-based prophylaxis. For patients at lower initial risk, pre-emptive therapy should be based on a management strategy that takes into account the presence of definite risk factors and the dynamics of candida colonisation. Among critically ill patients, azole prophylaxis is effective and is not associated with acquisition of resistance; it must be restricted to highly selected groups of patients at high risk only.

Eighty-three patients with 117 episodes of candidemia were reviewed to examine the clinically significant variables and the results of treatment for this problem. Mortality was 52%. Patients who had bacteremia either synchronously or metachronously in association with Candida species had poorer survival rates. Staphylococcal and enterococcal species were the most frequently associated bacteria. Patients with Candida parapsilosis had better survival rates than patients with other species. Portals of entry for fungemia were catheters, wounds, the urinary tract, and the peritoneal cavity, but were undefined in 54% of patients. Antifungal chemotherapy could not be identified as affecting the outcome in these patients. It is suggested that candidemia in most patients represents a failure of host defense, and that septicemia of either bacteria or fungi may arise from the gastrointestinal tract in critically ill, immunocompromised patients.

To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells, HIV-1-seropositive women were examined before and after treatment of Candida vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1 RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90 log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8; 95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating Candida and Trichomonas, respectively. These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation.

A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P =.04), and 13% and 34% of patients in the respective groups had Candida infections (P =.022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P =.024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%)(P =.12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.

Records of 65 surgical patients with positive fungal blood cultures were reviewed to address risk, overall mortality, and treatment. Negative urine cultures did not rule out sepsis. Staphylococcus epidermidis sepsis was present in 27 (42%) of the patients. In 70% of whom it occurred before or during fungemia. Increased mortality correlated with the use of multiple antibiotics, antibiotic use for prolonged periods, and with associated bacterial sepsis. Stopping antibiotic therapy did not reduce mortality. Amphotericin B reduced mortality in patients with dissemination, indicating that it is the treatment of choice for disseminated fungemia and that antibiotic therapy should not be discontinued when concomitant bacterial sepsis is present.

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.