Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists.

OBJECTIVE: To compare the management of invasive candidiasis between infectious disease and critical care specialists. DESIGN AND SETTING: Clinical case scenarios of invasive candidiasis were presented during interactive sessions at national specialty meetings. Participants responded to questions using an anonymous electronic voting system. PATIENTS AND PARTICIPANTS: Sixty-five infectious disease and 51 critical care physicians in Switzerland. RESULTS: Critical care specialists were more likely to ask advice from a colleague with expertise in the field of fungal infections to treat Candida glabrata (19.5% vs. 3.5%) and C. krusei (36.4% vs. 3.3%) candidemia. Most participants reported that they would change or remove a central venous catheter in the presence of candidemia, but 77.1% of critical care specialists would start concomitant antifungal treatment, compared to only 50% of infectious disease specialists. Similarly, more critical care specialists would start antifungal prophylaxis when Candida spp. are isolated from the peritoneal fluid at time of surgery for peritonitis resulting from bowel perforation (22.2% vs. 7.2%). The two groups equally considered Candida spp. as pathogens in tertiary peritonitis, but critical care specialists would more frequently use amphotericin B than fluconazole, caspofungin, or voriconazole. In mechanically ventilated patients the isolation of 10(4) Candida spp. from a bronchoalveolar lavage was considered a colonizing organism by 94.9% of infectious disease, compared to 46.8% of critical care specialists, with a marked difference in the use of antifungal agents (5.1% vs. 51%). CONCLUSIONS: These data highlight differences between management approaches for candidiasis in two groups of specialists, particularly in the reported use of antifungals.

Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000.

Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P<.001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P<.001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred.

Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography.

High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability. Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required. This constraint makes it difficult to determine drug levels when blood sample volumes are limited. However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction. This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC. Spiked FLC standards and unknowns were prepared in human and rat plasma. Samples (240 microl) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off. After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC. Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed. Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility. Cellulose filters were therefore used for the subsequent validation procedure. The quantification limit was 0.195 mgl(-1). Standard curves with a quadratic regression coefficient > or = 0.9999 were obtained in the concentration range of 0.195-100 mgl(-1). The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the +/-15% variation recommended by the current guidelines for the validation of analytical methods. Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents. Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 microl). The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate.

Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection.

BACKGROUND: Infections and their sequelae are a major cause of death among patients admitted to the surgical intensive care unit (ICU). Studies of passive immunotherapy with standard intravenous immune globulin and hyperimmune globulin directed against gram-negative core lipopolysaccharide to prevent gram-negative infections and their serious systemic complications have had equivocal results in such patients. METHODS: We performed a double-blind study to assess the efficacy of standard immune globulin and core-lipopolysaccharide hyperimmune globulin in preventing infections in surgical patients at high risk. The patients received standard immune globulin (400 mg per kilogram of body weight), hyperimmune globulin (400 mg per kilogram), or placebo (25 percent albumin, 8 ml per kilogram) weekly, for a maximum of four doses while in the ICU. RESULTS: A total of 352 patients were enrolled, and 329 could be evaluated. The number of patients in whom infections developed was significantly lower in the group receiving standard immune globulin than in the placebo group (36 of 109 vs. 53 of 112 patients, P = 0.03), as was the incidence of pneumonia (15 vs. 30 cases, P = 0.04), especially pneumonia due to gram-negative bacteria (5 vs. 16 cases, P = 0.02). The number of days spent in the ICU and the total days spent in the hospital were lower in the standard immune globulin group (medians of 2 and 7.5 days fewer; P = 0.02 and 0.06, respectively). In contrast, the hyperimmune globulin had no detectable prophylactic effect on infections (50 of 108 patients, with 25 cases of pneumonia). The rate of systemic infections and shock was similar in the three study groups, and hospital mortality did not differ significantly among them. CONCLUSIONS: Intravenous immune globulin given prophylactically to selected high-risk patients in the surgical ICU can reduce the incidence of infection. Core-lipopolysaccharide hyperimmune globulin is not effective in preventing gram-negative infections and their systemic complications.

Efficacy, tolerability and development of resistance in HIV-positive patients treated with fluconazole for secondary prevention of oropharyngeal candidiasis: a randomized, double-blind, placebo-controlled trial.

Over 37 months, we conducted a prospective double-blind, randomized study in a cohort of 138 HIV-infected patients to compare the effect of two different strategies on the prevention and treatment of oropharyngeal candidiasis relapses and on the development of clinical and microbiological resistance to fluconazole. Each episode was treated with a 7 day course of fluconazole 200 mg/day, followed by secondary prophylaxis with fluconazole 150 mg once weekly matched to placebo. The duration of the double-blind phase of the study, from the day of randomization to the first primary end-point, was 347 +/- 186 days for the fluconazole group and 196 +/- 128 days for the placebo group (P < 0.001). A total of 33 patients remained relapse-free during the course of the study. Clinical failure was observed in a total of five patients (four in the fluconazole group, one in the placebo group; P = 0.15). Microbiological resistance was recorded in 12 patients (eight in the fluconazole group, four in the placebo group; P = 0.20). There were no significant treatment group differences in microbiological resistance whether comparisons were made for all cases or for cases up to 1 month post-study. In the few patients who developed clinical and/or microbiological resistance, the cumulative dose of fluconazole before entry into the study was a mean value of 8.6 g (compared with 2.9 g in patients without clinical and/or microbiological resistance). In summary, patients treated with secondary prophylaxis suffered fewer relapses of oropharyngeal candidiasis. Development of resistant candidiasis (clinical and/or microbiological) was rarely seen in either group and its incidence was not significantly different.