[Cryptococcoma and amphotericin B. Therapy of cryptococcosis - animal experiments. 2nd Communication:...

Since cryptococcosis is characterized by cryptococcoma formation, the antimycotic effect of amphothericin B was examined in view of such pathological-anatomical conditions. In white mice (NMRI), cryptococcoma formation was induced by intramuscular injection of Cryptococcus neoformans strain W71 into the hind leg (STAIB, 1962), using a suspension (0.2 ml) containing approximately 2.8 times 10-7 cells/ml. The mice were treated daily with 1 mg amphotericin B in 5% dimethyl sulfoxide by gastric intubation. Course of infection and effectivity of therapy were assessed by microbiological and patho-histological examination of the organs. In the present paper (2nd Communication) comparative patho-histological results in mice, treated with amphotericin B either immediately or from the 16th day p.i. or not at all, are reported. In the non-treated animals the course of infection we controlled by sacrificing 2 animals per day from the 2nd to the 25th day. Cryptococcoma found in the muscle, fat, and connective tissue in the hind leg of these animals were characterized by the two different patho-histological alterations: a) Masses of encapsulated cryptococci side by side were filling a paucireactive or non-reactive reticular structure with blood capillaries. b) Non-specific granulomatous tissue. The fungi were less abundantly found as non-encapsulated cells. On the 5th day after infection the first alterations due to dissemination were found in the lungs, then in other parenchymatous organs. Under immediate amphotericin B-therapy, no cryptococcoma was found at the place of infection; after a therapy of 30 days duration, C. neoformans could be detected in small conglomerates of non-encapsulated cells in muscle, fat and connective tissue. Histologically, a septic dissemination of the agent could not be found in this group. After a therapy of 25 days duration a shrinking of cryptococcoma was observed in animals treated from the 15th day after infection. Presumably this was caused by a loss of capsule and formation of non-specific granulomatous tissue. In the surroundings of blood vessels non-encapsulated cells were detectable. After therapy with amphotericin B, single cryptococci e.g. such disseminated into the lungs were increasingly showing morphological alterations which might be explained as forms of degeneration. The animal experiment in connection with microbiological and patho-histological follow-up studies is discussed with a view to the therapy of cryptococcosis in man. Because of the variable virulence of C. neoformans it has to be mentioned that this experiment was carried out with a strain of C. neoformans characterized by its capability to form cryptococcoma in mice.