We studied fungemia over time in outbred mice infected with Cryptococcus neoformans and looked at its relationship with the intravenous (i.v.) inoculum size, tissue burden and survival. Fungemia was evaluated by culture of 10 ml of peripheral blood from living mice or by culture of buffy coats from sacrificed animals. For all inoculum sizes studied, fungemia could last several weeks after the i.v. inoculation. Individual susceptibility of outbred mice to cryptococcal infection was evidenced by variations in the course, duration and magnitude of fungemia and tissue localizations. These results suggest that the fungus can recirculate after the initial i.v. inoculation. Fungemia, assessed by culture of buffy coats, correlated with the extent of infection in the spleen, lung or brain (PB 0·001) on day 1 after inoculation but only with yeast burden in lung or spleen on day 8, thus demonstrating that brain reacts differently to C. neoformans infection than other organs. Comparison of blood culture techniques and examination of smears suggest that cryptococci might circulate within leucocytes. Finally, quantitative blood cultures may accurately assess the fungal load during experimental cryptococcosis.

The time of initiation of fluconazole treatment with or without dexamethasone, and the impact on mycological outcome and drug pharmacokinetics were assessed in a murine model of disseminated cryptococcosis. Non-infected mice and mice with disseminated cryptococcosis were given saline, dexamethasone, or fluconazole +/- dexamethasone, 1 or 8 days after infection. Cfus were counted in tissues, and fluconazole concentrations were determined in plasma and tissues by HPLC and a bioassay. Despite fluconazole tissue and plasma concentrations which were above the minimal inhibitory concentration, the numbers of cfus in brain and lung tissues were reduced after early (P = 0.002 and 0.04, respectively), but not after late fluconazole treatment. The administration of dexamethasone did not have a deleterious effect on the number of cfus, fluconazole pharmacokinetics or antifungal activity. In conclusion, the size of the fungal burden influences the effective level of fluconazole activity in lung and brain. These results strongly suggest that potential antifungal agents should be studied following both early and late administration in experimental cryptococcosis.

Background Kodamaea ohmeri is a yeast is frequently mistaken for Candida, which belongs to the same family. This micro-organism has been reported to cause life-threatening infections in humans. Case presentation A 81-year-old woman developed a severe fungemic pulmonary infection due to Kodamaea ohmeri that was identified from bronchoalveolar fluid and blood cultures, which is unusual in immunocompetent patients. Because K. ohmeri was first wrongly identified as Candida albicans , the patient inadequately received caspofungin, which was clinically ineffective, especially as the strain was resistant to echinocandins. Clinical cure was obtained after treatment was switched to voriconazole. Conclusions An increasing number of serious infections due to K. ohmeri has been reported in the literature, but the correct identification of this micro-organism remains difficult.

No abstract

We studied fungemia over time in outbred mice infected with Cryptococcus neoformans and looked at its relationship with the intravenous (i.v.) inoculum size, tissue burden and survival. Fungemia was evaluated by culture of 10 μl of peripheral blood from living mice or by culture of buffy coats from sacrificed animals. For all inoculum sizes studied, fungemia could last several weeks after the i.v. inoculation. Individual susceptibility of outbred mice to cryptococcal infection was evidenced by variations in the course, duration and magnitude of fungemia and tissue localizations. These results suggest that the fungus can recirculate after the initial i.v. inoculation. Fungemia, assessed by culture of buffy coats, correlated with the extent of infection in the spleen, lung or brain (P≪0·001) on day 1 after inoculation but only with yeast burden in lung or spleen on day 8, thus demonstrating that brain reacts differently to C. neoformans infection than other organs. Comparison of blood culture techniques and examination of smears suggest that cryptococci might circulate within leucocytes. Finally, quantitative blood cultures may accurately assess the fungal load during experimental cryptococcosis.