No abstract

The correlation between antifungal susceptibility testing and in vivo response to antifungal therapy was examined in experimental murine candidiasis. In vitro susceptibility testing was done using a microbroth dilution method. Twenty-two Candida albicans, 4 Candida lusitaniae, and 2 Candida krusei isolates were tested against fluconazole, flucytosine, and amphotericin B. In vivo antifungal activity was tested in murine hematogenous candidiasis. Normal CF1 mice were infected with each of the C. albicans strains; immunosuppressed CF1 mice were inoculated with C. lusitaniae or C. krusei. Mice received various doses of antifungal agents, and survival was monitored for 21 days. Kidney fungal burden was examined on day 4. Antifungal therapy significantly prolonged survival and reduced tissue counts in animals infected with organisms susceptible to the agent tested (P < .05). In vitro resistance to a drug predicted its lack of in vivo activity. These results appear to correlate well with outcome of murine hematogenous candidiasis.

We assessed the activities of amphotericin B deoxycholate, liposomal amphotericin B, fluconazole, and SCH 39304 against 10 strains of Trichosporon beigelii in mice with hematogenous infections. Cyclophosphamideimmunosuppressed CF1 male mice were challenged intravenously with a lethal inoculum of T. beigelii (5 x 106 conidia per mouse) and were assigned to different treatment groups or were left untreated. Amphotericin B deoxycholate (1 mg/kg of body weight and liposomal amphotericin B (1, 5, and 10 mg/kg) were given parenteraily once daily. Escalating doses (5, 10, and 20 mg/kg/day) of fluconazole and SCH 39304 were tested.We also compared the activity of amphotericin B deoxycholate plus fluconazole (1 and 10 mg/kg/day, respectively) with that of each agent alone. Fluconazole significantly prolonged the survival of mice infected with each of the 10 strains tested. Amphotericin B deoxycholate achieved various responses, improving the outcomes in mice infected with seven of the strains. Liposomal amphotericin B was not more effective than amphotericin B deoxycholate against the two strains tested. Both fluconazole and SCH 39304 reduced the kidney fungal counts in a dose-dependent pattern, with SCH 39304 being more active than fluconazole against one of the two strains tested. The activity of the combination of amphotericin B deoxycholate plus fluconazole appeared to be superior to that of either agent alone, especially in reducing the kidney fungal burden.Fluconazole is more active than amphotericin B deoxycholate against experimental murine trichosporonosis.Trichosporon beigelii is increasingly recognized as a fungal opportunistic pathogen. Infection with this pathogen is frequently disseminated and carries a high mortality rate, particularly in the setting of immunosuppression (3, 6-11, 13, 16-26, 28, 32). The treatment of choice for disseminated trichosporonosis remains to be established. While amphotericin B is active against a variety of fungal infections, the agent appears to have limited activity against T. beigelii (32). In recent years, several antifungal agents have become available. These include liposomal amphotericin B and the triazoles fluconazole and SCH 39304 (2,4,5). In the present work, we evaluated these antifungal agents and the role of combination antifungal chemotherapy in the treatment of disseminated murine trichosporonosis. We sought to determine whether triazoles were as efficacious as amphotericin B deoxycholate and whether liposomal amphotericin B was superior to amphotericin B deoxycholate. Additionally, we tried to determine whether a dose response to triazole therapy was present and whether the combination of a triazole with amphotericin B was associated with antagonism.MATERLIALS AND METHODS Animals. Outbred CF1 male mice (average weight, 25 g; Harlan Breeding Laboratories, Indianapolis, Ind.) were used. All mice were housed in standard boxes with corncob bedding and were given food and water ad libitum. Five mice were housed in each box.Organisms and culture conditions. Ten T. be...

ABSTRACT.Purpose: The intraocular pressure (IOP) is determined by a dynamic equilibrium between the production and outflow of the aqueous humour. The relationship between IOP and the outflow rate through the conventional and unconventional pathway is quantified by the outflow facility coefficient (C). The purpose of this study is to employ a direct (manometric) tonographic technique and determine C as well as its inverse, resistance (R), as a function of IOP in the living human eye. Methods: Nineteen cataract patients were enrolled in the study. An intraoperative manometric device was used to measure IOP. After cannulation of the anterior chamber, the IOP was increased by infusion of controlled amounts of saline solution. At 40 mmHg, the infusion stopped, and a pressure sensor recorded the IOP. The measured pressure-volume relationship was considered in order to convert pressure changes to corresponding ocular volume changes. An appropriate mathematical model was applied to calculate C and (its inverse), R. Results: The average C was 0.0672 AE 0.0296 ll/min/mmHg at 40 mmHg and 0.2652 AE 0.1164 ll/min/mmHg at 20 mmHg. There was a strong dependence of coefficient C on IOP in all subjects (p < 0.001). The corresponding values for R were 17.9 AE 11.17 min mmHg/ll at 40 mmHg and 4.51 AE 2.69 min mmHg/ ll at 20 mmHg. Conclusion: This study provides measurement of outflow facility and its dependence with pressure in healthy living human eyes. This relation is shown to be non-linear, using a direct manometric method.