The postantifungal effect (PAFE) of fluconazole, MK-0991, LY303366, and amphotericin B was determined against isolates of Candida albicans and Cryptococcus neoformans. Concentrations ranging from 0.125 to 4 times the MIC were tested following exposure to the antifungal for 0.25 to 1 h. Combinations of azole and echinocandin antifungals (MK-0991 and LY303366) were tested against C. neoformans. Fluconazole displayed no measurable PAFE against Candida albicans or Cryptococcus neoformans, either alone or in combination with either echinocandin antifungal. MK-0991, LY303366, and amphotericin B displayed a prolonged PAFE of greater than 12 h against Candida spp. when tested at concentrations above the MIC for the organism and 0 to 2 h when tested at concentrations below the MIC for the organism.As the frequency of fungal infections increases, there is a need for new antifungal agents and increased understanding of the pharmacodynamic properties of these agents. The echinocandin antifungals represent a new class of antifungal agents that inhibit fungal growth by inhibition of glucan synthase, an enzyme responsible for fungal cell wall formation. The activity of these agents has been described as either fungicidal or fungistatic, depending on the isolate and test conditions (1, 3). Amphotericin B (AMB), the mainstay of therapy for fungal infections, is described as having concentration-dependent fungicidal activity (8). In comparison, the azole antifungal agents are described as exhibiting concentration-independent fungistatic activity (8).The postantifungal effect (PAFE) is the suppression of fungal growth that persists after limited exposure to an antifungal agent. This has been described for the azole antifungals and AMB, but not for the echinocandin antifungal agents (10, 12). The PAFE may have clinical relevance to the design of dosing regimens for new antifungal agents such as the echinocandins. Antimicrobials with long PAFEs may be given less frequently than antimicrobials with short PAFEs, which may require more frequent administration.We sought to determine the PAFEs of echinocandin antifungals MK-0991 and LY303366 and compare them to the PAFEs of AMB and fluconazole (FLC). Secondarily, we sought to determine if the addition of an echinocandin antifungal would enhance the relatively short PAFE generally observed with FLC.(This work was presented at the American College of Clinical Pharmacy Annual Meeting, Phoenix, Ariz., 9 to 12 November 1997.)Stock solutions of AMB (Sigma Chemical Company, St. Louis, Mo.), FLC (Pfizer, Inc., New York, N.Y.), MK-0991 (Merck and Co., Inc., Rahway, N.J.), and LY303366 (Eli Lilly and Co., Indianapolis, Ind.) were prepared in RPMI 1640 medium (Sigma) buffered to a pH of 7.0 with 0.165 M morpholinopropanesulfonic acid (MOPS). All antifungals were solubilized with less than a 1% (vol/vol) final volume of dimethyl sulfoxide.One clinical isolate, OY31.5, and one American Type Culture Collection isolate, 90028, of Candida albicans were selected for study based upon extensive experience ...

This study was designed to examine the effects of antifungal carryover, agitation, and starting inoculum on the results of time-kill tests conducted with various Candida species. Two isolates each of Candida albicans, Candida tropicalis, and Candida glabrata were utilized. Test antifungal agents included fluconazole, amphotericin B, and LY303366. Time-kill tests were conducted in RPMI 1640 medium buffered with morpholinepropanesulfonic acid (MOPS) to a pH of 7.0 and incubated at 35°C. Prior to testing, the existence of antifungal carryover was evaluated at antifungal concentrations ranging from 1× to 16× MIC by four plating methods: direct plating of 10, 30, and 100 μl of test suspension and filtration of 30 μl of test suspension through a 0.45-μm-pore-size filter. Time-kill curves were performed with each isolate at drug concentrations equal to 2× MIC, using a starting inoculum of approximately 105 CFU/ml, and incubated with or without agitation. Last, inoculum experiments were conducted over three ranges of starting inocula: 5 × 102 to 1 × 104, >1 × 104 to 1 × 106, and >1 × 106 to 1 × 108 CFU/ml. Significant antifungal carryover (>25% reduction in CFU/milliliter from the control value) was observed with amphotericin B and fluconazole; however, carryover was eliminated with filtration. Agitation did not appreciably affect results. The starting inoculum did not significantly affect the activity of fluconazole or amphotericin B; however, the activity of LY303366 may be influenced by the starting inoculum. Before antifungal time-kill curve methods are routinely employed by investigators, methodology should be scrutinized and standardized procedures should be developed.

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Pharmacists are key partners in antimicrobial stewardship efforts, yet their degree of education on and attitudes toward this topic during training are not well documented. An electronic survey measuring knowledge and attitudes regarding antimicrobial use and resistance was administered to graduating pharmacy students at 12 US schools of pharmacy. Of 1445 pharmacy students, 579 (40%) completed the survey. The vast majority (94%) believed that strong knowledge of antimicrobials was important for their pharmacy careers, and 89% desired more education on appropriate antimicrobial use. Most students (84%) considered their pharmacy education regarding antimicrobials useful or very useful, but there was significant variability on perceptions of preparation for most antimicrobial stewardship activities according to the students' school. The mean number of correct answers on a section of 11 knowledge questions was 5.8 (standard deviation 2.0; P value for score between schools <.001). On multivariable linear regression analysis, significant predictors of a higher knowledge score were pharmacy school attended, planned postgraduate training, completion of a clinical rotation in infectious diseases, perception of pharmacy school education as useful, use of resources to answer the knowledge questions, and use of Infectious Diseases Society of America guidelines and smartphone applications as frequent resources for learning about antimicrobials. Pharmacy students perceive antimicrobial stewardship to be an important healthcare issue and desire more education on the subject. Student perceptions of antimicrobial coursework and actual antimicrobial knowledge scores significantly varied by the school of pharmacy attended. Sharing of best practices among institutions may enhance the preparation of future pharmacists to contribute to effective antimicrobial stewardship.