The risk of opportunistic infections is greatly increased in patients who are immunocompromised due to AIDS, cancer chemotherapy and organ or bone marrow transplantation. Candida albicans is often associated with serious systemic fungal infections, however other Candida species such as Candida krusei, Candida tropicalis and Candida glabrata, as well as Cryptococcus neoformans and filamentous fungi such as Aspergillus, have also emerged as clinically significant fungal pathogens. Two triazole antifungal agents, fluconazole and itraconazole, were introduced over a decade ago and since then have been used extensively for the prophylaxis and treatment of a variety of fungal infections. Although both drugs are effective and have their place in therapy, limitations regarding the utility of these agents do exist. For example, fluconazole is not effective for the prophylaxis or treatment of Aspergillus species and has limited activity against C. krusei and C. glabrata. The use of itraconazole has been limited secondary to concerns regarding unpredictable bioavailability. The rising incidence of fungal infections and the reported increase of non-albicans candidal infections noted over the past two decades highlight the need for new antifungal agents with improved spectra of activity. Several new triazole agents are in various phases of preclinical and clinical trials and may be available for human use in the near future. Three such agents voriconazole, posaconazole and ravuconazole are reviewed and compared with existing agents.

We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, <0.12 g/ml), nine isolates exhibiting low-level, mefA-mediated resistance (clarithromycin and azithromycin MICs, 0.5 to 32 g/ml), and five isolates expressing high-level, ermB-mediated macrolide resistance (clarithromycin and azithromycin MICs, >64 g/ml).

Four Candida albicans isolates and six non-albicans Candida isolates were evaluated by time-kill methods to characterize the relationship between nystatin concentrations, the rate and extent of fungicidal activity, and the postantifungal effect (PAFE). Against Candida species, nystatin exhibits concentration-dependent fungicidal activity and a pronounced PAFE.The incidence of superficial infections and disseminated fungal infections has steadily risen over the past decade (1). Candida now ranks as the fourth most frequently encountered microbe among nosocomial bloodstream pathogens (11). Nystatin, a polyene antifungal agent produced by Streptomyces noursei, exhibits antifungal activity against a broad spectrum of fungal pathogens. Clinical studies have reported nystatin to be effective against azole-resistant strains of Candida and, in some cases, amphotericin B-resistant strains of Candida albicans (1, 6).Currently, knowledge of the pharmacodynamic characteristics of nystatin is limited. We have previously described the in vitro concentration-response characteristics of several antifungal agents, including fluconazole, flucytosine, amphotericin B, and the echinocandins (3-5, 9). Knowledge of the concentration-effect relationship allows for description of the rate and extent of antifungal activity and provides a more rational basis for determining optimal dosing regimens. The purpose of this study was twofold: (i) to describe the concentration-effect relationship of nystatin for a variety of Candida species, and (ii) to characterize the postantifungal effect (PAFE) of nystatin on these isolates.Nystatin (Sigma Chemical Company, St. Louis, Mo.) was utilized for MIC determination, carryover demonstrations, and time-kill curve procedures. Dimethyl sulfoxide (DMSO) was used to aid in solubilizing nystatin. The final concentration of DMSO comprised less than 1% (vol/vol) of the total solution concentration used for each experiment in the study. Growth curves have been determined in previous studies and displayed no inhibition of fungal growth in the presence of DMSO when used at similar concentrations (2, 9). Stock solution was separated into unit-of-use vials and frozen at Ϫ70°C until needed.Ten Candida isolates were obtained from the Division of Medical Microbiology, Department of Pathology, The University of Iowa College of Medicine, for use in this study. The strains used included four Candida albicans strains (OY31.5, 142-5609, 2733A, and ATCC 90028) and two strains each of Candida glabrata (582 and 350), Candida krusei (37-5696A, ATCC 6258), and Candida tropicalis (2697 and 3829). Test isolates were stored in sterile water at room temperature until used.The MIC for each isolate was determined by broth microdilution techniques as outlined by the National Committee for Clinical Laboratory Standards (10). The MIC of nystatin was defined as the lowest concentration of drug that resulted in complete inhibition of visible fungal growth at 48 h.Prior to performing time-kill studies, carryover effects were examined as ...

With the rising frequency of fungal infections, as well as increasing reports of resistance to antifungal agents, it is imperative that clinically applicable antifungal susceptibility testing be available. In 1997 the National Committee for Clinical Laboratory Standards published standard guidelines for antifungal susceptibility testing of Candida sp and Cryptococcus neoformans with amphotericin B, flucytosine, fluconazole, itraconazole, and ketoconazole. Although the methods are standard, they are time consuming, can be difficult to interpret, and are approved only for testing limited organisms and drugs. Modifications to the methods and alternative approaches have been proposed to make these tests more convenient and efficient, applicable to a greater number of species, and appropriate for performing in the clinical laboratory.