Prophylaxis or preemptive therapy of invasive candidiasis in the intensive care unit?
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Candidiasis↗
Biomedical subjects
Luis Ostrosky-Zeichner
Publications and source records attributed to Luis Ostrosky-Zeichner.
Therapy of common superficial fungal infections.
Superficial fungal infections are common, especially onychomycosis, dermatophytoses, and superficial Candida infections. Most superficial fungal infections are treated with topical antifungal agents unless the infection covers an extensive area or is resistant to initial therapy. Onychomycosis often requires systemic therapy with griseofulvin, itraconazole, or terbinafine. The objective of this review is to provide the practicing dermatologist with the recommended available therapy for the treatment of common superficial fungal infections.
Antifungal Agents↗
Combination antifungal therapy.
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Animals↗
In vitro activity of anidulafungin against selected clinically important mold isolates.
In this study, we evaluated the in vitro activity of anidulafungin against selected mold isolates. Anidulafungin showed promising activity against Bipolaris spicifera, Exophiala jeanselmei, Fonsecaea pedrosoi, Madurella mycetomatis, Penicillium marneffei, Phialophora verrucosa, Pseudallescheria boydii, Sporothrix schenckii, and Wangiella dermatitidis.
Amphotericin B↗
Pharmacokinetics of intravenous itraconazole in stable hemodialysis patients.
The pharmacokinetics of intravenous itraconazole (ITC) was studied in dialysis patients. Dialysis had no effect on the half-life and clearance of ITC or OH-ITC. However, dialysis allowed the clearance of hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The area under the concentration-time curve from time zero to infinity (AUC(0- infinity)) for HP-beta-CD administered before dialysis was lower than the AUC(0- infinity) when it was administered after dialysis (P < 0.01). Administration of ITC intravenously just prior to hemodialysis appears to produce adequate systemic exposures of ITC and OH-ITC while allowing dialysis clearance of HP-beta-CD. Studies of multiple administrations are warranted.
2-Hydroxypropyl-beta-cyclodextrin↗
Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species.
Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC(2)) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode +/- one dilution range across all 17 laboratories. MIC(2) at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.
Antifungal Agents↗
Novel approaches to antifungal prophylaxis.
Antifungal prophylaxis represents a significant advance in the management of patients at risk from fungal infections in a variety of settings. Identification of patients at the highest risk and the utilisation of safe and effective drugs maximises the benefits of prophylaxis. Situations in which antifungal prophylaxis has been shown to be useful are bone marrow transplantation, liver and lung transplantation, surgical and neonatal intensive care units, secondary prophylaxis of fungal infections associated with HIV and neutropenia associated haematological malignancies and their treatment. New antifungal agents, such as the echinocandins and the new azoles, are available and have a potential role in antifungal prophylaxis. Future studies should evaluate which strategy is more useful; prophylaxis or pre-emptive therapy.
Acquired Immunodeficiency Syndrome↗
Amphotericin B: time for a new "gold standard".
When introduced in 1959, amphotericin B deoxycholate (AmBD) was clearly a life-saving drug. Randomized studies demonstrating its efficacy were not thought to be necessary, and it was granted indications for many invasive fungal infections. Despite its formidable toxicities, AmBD is thus often used as the primary comparator in studies of invasive fungal infections. Safer lipid-based versions of amphotericin B (AmB) have been introduced, but difficulties with studying these agents generally led to licensure for salvage therapy, not primary therapy. However, the cumulative clinical experience to date with the lipid-based preparations is now adequate to demonstrate that these agents are no less active than AmBD, and, for some infections, it can now be stated that specific lipid-based preparations of AmB are superior to AmBD. Given their superior safety profiles, these preparations can now be considered suitable replacements for AmBD for primary therapy for many invasive fungal infections in clinical practice and research.
Amphotericin B↗
Peritonitis due to Aspergillus and zygomycetes in patients undergoing peritoneal dialysis: report of 2 cases and review of the literature.
Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) has been associated with high mortality and high CAPD-discontinuation rates. Most cases are due to Candida spp. while Aspergillus spp. and zygomycetes have only rarely been implicated. We report one case each of CAPD-related peritonitis caused by Aspergillus terreus and Mucor sp., which have previously been described in the literature once and twice, respectively. The former had a slowly progressive course, did not respond to amphotericin B (AB), and died; the latter improved after a prolonged course of liposomal-AB. Among reported cases of CAPD-related peritonitis due to molds (22 Aspergillus spp. and seven zygomycetes), previous bacterial peritonitis was a common event, the related mortality associated with Aspergillus and zygomycetes was 27% and 57%, respectively, prompt removal of the Tenckoff catheter was critical for survival, and most patients were not able to resume CAPD.
Adult↗
New approaches to the risk of Candida in the intensive care unit.
PURPOSE OF REVIEW: Candidemia is the fourth most common bloodstream infection in the United States with similar trends reported worldwide. This infection is particularly relevant in the intensive care setting, and is independently associated with increased morbidity and mortality. Identification of patients at risk and developing new prophylactic strategies is a priority area of research. This review focuses on recent advances in risk identification and the groundwork for prophylaxis of invasive candidiasis in the intensive care setting. RECENT FINDINGS: Although risk factors for invasive candidiasis have been clearly identified (such as colonization, length of stay, use of parenteral nutrition, antibiotics, central lines, and abdominal surgery), there are few risk assessment strategies that clearly define or predict a population at high risk of getting this disease. Currently available risk assessment strategies are yet to be validated in multiple centers and settings. Geographically limited or population specific clinical trials (such as surgical patients) have shown early indications that antifungal prophylaxis is useful in reducing the incidence of invasive candidiasis by more than 50% in units with high incidence of infection, or in carefully selected high-risk patients. Interesting advances in non-culture diagnostic methods and surrogate markers of infection may also have an impact in early identification of infection and preemptive treatment. SUMMARY: Invasive candidiasis is a relevant problem in the intensive care setting. Better risk assessment strategies will permit identification of the subpopulations of patients that would benefit from prophylactic antifungal therapy the most, having the potential to save millions of lives and dollars.
Candidiasis↗
Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States.
Candida bloodstream isolates (n = 2,000) from two multicenter clinical trials carried out by the National Institute of Allergy and Infectious Diseases Mycoses Study Group between 1995 and 1999 were tested against amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), caspofungin (CFG), micafungin (MFG), and anidulafungin (AFG) using the NCCLS M27-A2 microdilution method. All drugs were tested in the NCCLS-specified RPMI 1640 medium except for AMB, which was tested in antibiotic medium 3. A sample of isolates was also tested in RPMI 1640 supplemented to 2% glucose and by using the diluent polyethylene glycol (PEG) in lieu of dimethyl sulfoxide for those drugs insoluble in water. Glucose supplementation tended to elevate the MIC, whereas using PEG tended to decrease the MIC. Trailing growth occurred frequently with azoles. Isolates were generally susceptible to AMB, 5FC, and FLU. Rates of resistance to ITR approached 20%. Although no established interpretative breakpoints are available for the candins (CFG, MFG, and AFG) and the new azoles (VOR and POS), they all exhibited excellent antifungal activity, even for those strains resistant to the other aforementioned agents.
Analysis of Variance↗
Correlation between E-test, disk diffusion, and microdilution methods for antifungal susceptibility testing of fluconazole and voriconazole.
The activities of fluconazole and voriconazole against isolates of Candida spp. (n = 400) were tested by the E-test, disk diffusion, and the National Committee for Clinical Laboratory Standards (NCCLS) M27-A2 broth microdilution-based reference methods. More than 96% of isolates found to be susceptible to fluconazole by the reference method were identified as susceptible by the agar-based methods. Lesser degrees of correlation with the reference method were seen for isolates identified as resistant by the agar-based methods. Interpretive categories are not available for voriconazole, but results qualitatively similar to those for fluconazole were seen. The agar-based E-test and disk diffusion methods are reliable alternatives to the NCCLS M27-A2 reference microdilution method for isolates that test susceptible to fluconazole.
Antifungal Agents↗
Disk diffusion-based methods for determining Candida parapsilosis susceptibility to anidulafungin.
Zone diameters for anidulafungin by disk diffusion for 139 isolates of C. parapsilosis were compared with MICs by NCCLS M27-A2 broth microdilution. The comparison was poor unless the disks were prepared by dissolving anidulafungin in 1% dimethyl sulfoxide plus 0.1% Tween 80 and testing on Mueller-Hinton agar flooded with glucose and methylene blue.
Anidulafungin↗
Deeply invasive candidiasis.
The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology. Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease. Although identification to the species level and antifungal susceptibility testing should guide therapy, at this time amphotericin B preparations are the usual initial therapy for severe life-threatening disease. Azole therapy has an expanding body of evidence that proves it is as effective as and safer than amphotericin B therapy. Some forms of candidiasis (e.g., those with ocular, bone, or heart involvement) require a combined medical and surgical approach.
Antibiotic Prophylaxis↗
In vitro activities of investigational triazoles against Fusarium species: effects of inoculum size and incubation time on broth microdilution susceptibility test results.
We studied the effects of inoculum size and incubation time on the susceptibility testing results for various antifungal agents against 22 Fusarium isolates by the NCCLS microdilution method. Increased inoculum size and extended incubation time resulted in elevated MICs. Posaconazole and voriconazole exhibited promising antifungal activities.
Antifungal Agents↗
In vitro antifungal susceptibilities of Trichosporon species.
The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of Trichosporon spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC ratios were observed for voriconazole, posaconazole, and ravuconazole, suggesting fungicidal activity.
Amphotericin B↗
Effect of the echinocandin caspofungin on expression of Candida albicans secretory aspartyl proteinases and phospholipase in vitro.
Although the echinocandin caspofungin primarily inhibits the synthesis of cell wall 1,3-beta-D-glucan, its fungicidal activity could also potentially perturb the expression of virulence factors involved in the ability of Candida albicans to cause infection. Expression of the C. albicans secretory aspartyl proteinase (SAP) and phospholipase B (PLB) virulence genes was determined by reverse transcription-PCR after the addition of caspofungin to cells grown for 15 h in Sabouraud dextrose broth. In cells that remained viable, expression of SAP1 to SAP3, SAP7 to SAP9, and PLB1 was unaltered after exposure to fungicidal concentrations (4 to 16 micro g/ml) of caspofungin over a period of 7 h. However, expression of SAP5 increased steadily beginning 1 h after exposure to caspofungin. These results indicate that caspofungin is rapidly fungicidal against C. albicans, before any suppression of SAP or PLB1 gene expression can occur.
Anti-Bacterial Agents↗
In vitro activity of nystatin compared with those of liposomal nystatin, amphotericin B, and fluconazole against clinical Candida isolates.
We investigated the in vitro activity of nystatin and liposomal nystatin against 103 Candida isolates to determine the effect of both time and medium on MICs. We also compared the nystatin MICs with those of amphotericin B and fluconazole. Testing was performed in accordance with the National Committee for Clinical Laboratory Standards M27-A microdilution methodology with RPMI 1640, RPMI 1640 supplemented with glucose to 2% (RPMI-2), and antibiotic medium 3 supplemented with glucose to 2% (AM3). While nystatin MICs were similar to or slightly lower than liposomal nystatin MICs in RPMI 1640 and RPMI-2, they were markedly higher than liposomal nystatin MICs in AM3. Use of AM3 and determination of the MIC after 24 h of incubation provided a slightly wider range of liposomal nystatin MICs (0.06 to >16 microg/ml). Under these conditions, the MICs at which 90% of isolates were inhibited of nystatin and liposomal nystatin were 2 and 1 microg/ml, respectively. Nystatin and liposomal nystatin in general showed good activity against all Candida spp. tested. Although the MICs of nystatin and liposomal nystatin tended to rise in parallel with the amphotericin B MICs, nystatin and liposomal nystatin MICs of 1 to 2 and 0.5 to 1 microg/ml, respectively, were obtained for seven and six, respectively, of nine isolates for which amphotericin B MICs were >or=0.25 microg/ml. No correlation between fluconazole and nystatin or liposomal nystatin MICs was observed. As amphotericin B MICs of >or=0.25 microg/ml correlate with in vitro resistance, these results suggest that liposomal nystatin might have activity against some amphotericin B-resistant isolates. In vivo testing in animal models is required for clarification of this issue.
Amphotericin B↗