Michael L. Corrado

Susceptibility of dematiaceous fungi to amphotericin B, miconazole, ketoconazole, flucytosine and rifampin alone and in combination

The dematiaceous fungi comprise a group of organisms that are deeply pigmented and found in soil or on decaying organic material, such as wood. The majority of infections with these fungi presumably results from traumatic inoculation. Although various forms of infection have been appreciated for some time, none of the presently available antifungal drugs have been shown to have predictable activity against these organisms. We report on the activity in vitro of various antifungal agents alone and in combination against various dematiaceous fungi.

Subcutaneous infection with Phialophora richardsiae and its susceptibility to 5-fluorocytosine, amphotericin B and miconazole

Two patients are described with subcutaneous infections due to Phialophora richardsiae. Both were diabetics and originally came from subtropical areas. One of the patients had a cystic lesion which was well encapsulated while the other had a large ulcerating lesion with draining sinus tracts. The organisms were found to be susceptible to cycloheximide but resistant to 5-fluorocytosine, miconazole and amphotericin B. There was some variability in the degree of resistance depending upon whether the primary or secondary phialoconidia were tested. While simple excision appears curative for the solitary cystic type of lesion, therapy of the ulcerating form of the disease remains problematic.

The course of cryptococcal capsular polysaccharide antigenemia/human cryptococcal polysaccharide elimination kinetics

SummaryThe detection of cryptococcal polysaccharides in the serum is diagnostic of cryptococcosis in the absence of rheumatoid factor. The significance of the continued detection of this antigen in the serum during antifungal therapy is not known. Prolonged anti-genemia might indicate ongoing active infection, delayed clearance of the polysaccharides from the blood, or continued release of the polysaccharide antigens from a reservoir of nonviable organisms. In seven cases of cryptococcosis with prolonged and high levels of cryptococcal polysaccharide antigenemia, the courses of antigenemia were determined. During the convalescent phase, the T1/2s were approximately 48 hours for the antigen clearance in all the cases studied. The polysaccharide antigens recovered from the serum of one patient had molecular weights of greater than 200,000 daltons. In rabbits, a single intravenous injection of cryptococcal capsular polysaccharides showed a similarly slow clearance of the antigen with a T1/2 of approximately 24 to 48 hours. These data suggest that adequately treated cases of cryptococcosis may have a predictable rate of antigen clearance from the serum during convalescence.ZusammenfassungDer Nachweis von Cryptococcus-Polysacchariden im Serum sichert — sofern kein Rheumafaktor vorliegt — die Diagnose der Kryptokokkose. Es ist nicht bekannt, welche Bedeutung der Persistenz dieses Antigens im Serum unter der Therapie mit einem Antimykotikum zukommt. Eine prolongierte Antigenämie könnte das Zeichen für eine fortschreitende aktive Infektion, für die verzögerte Elimination der Polysaccharide aus dem Blut oder für eine anhaltende Freisetzung von Polysaccharidantigen aus einem Reservoir nicht lebensfähiger Organismen sein. Der Verlauf der Antigenämie wurde bei sieben Fällen von lange anhaltenden hohen Spiegeln von Cryptococcus-Polysaccharidantigen im Blut bestimmt. Während der Rekonvaleszenz betrug T1/2 für die Antigenclearance in allen untersuchten Fällen etwa 48 Stunden. Die im Serum eines Patienten nachgewiesenen Polysacharidantigene hatten Molekulargewichte von über 200 000 Dalton. Bei Kaninchen war nach der intravenösen Injektion einer Einzeldosis von Cryptococcus-Kapselpolysaccharid eine ähnlich langsame Antigenclearance mit einer T1/2 von 24–48 Stunden nachzuweisen. Daraus läßt sich schließen, daß adäquat behandelte Fälle von Kryptokokkose während der Erholungsphase eine vorausbestimmbare Serum-Antigenclearance haben.

Susceptibility of Zygomycetes to human serum.

Seven members of the class Zygomycetes were tested for serum susceptibility. Five of the isolates were inhibited to different degrees by pooled fresh human serum. Heating the serum at 56 degrees C for 30 min to inactivate complement did not abolish the inhibitory activity in the serum. Members of the genera Cunninghamella and Absidia appeared most susceptable to the inhibitory effects of serum while members of the genus Rhizopus were most resistant. One isolate of R. arrhizus appeared to have enhanced growth in the presence of human serum. Our findings suggest certain species of the class Zygomycetes are strongly inhibited by serum, and this may account for the rarity of human infections by these species.