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Biomedical subjects

H J Shadomy

Publications and source records attributed to H J Shadomy.

At least 19 recordsLinked to original sources

Infection due to the fungus Acremonium (cephalosporium).

Human infections due to fungi belonging to the genus Acremonium occur uncommonly, but unlike infections due to other filamentous fungi, usually affect immunocompetent individuals. Mycetoma, which usually develops following trauma, is the most common infection caused by Acremonium spp. Other sites of infection include the eye (generally following abrogation of ocular defenses), colonizing disease of the lung and gastrointestinal tract, as well as locally invasive infections such as osteomyelitis, sinusitis, arthritis, and peritonitis. Pneumonia and disseminated infections including meningitis, endocarditis, and cerebritis rarely have been reported. Optimal treatment of acremonium infections is not well defined both because infections due to these organisms are rare, and because many reports antedate effective antifungal therapy. In addition, susceptibility testing of filamentous fungi is poorly standardized, and in vitro sensitivity may not correlate with clinical response. Based on anecdotal reports, treatment of most invasive acremonium infections requires a combination of surgical intervention, when possible, and a regimen of amphotericin B. Some azoles also display inhibitory activity. Until more details are available regarding susceptibility of these organisms to antifungal agents, amphotericin B is recommended as initial therapy with the addition of either ketoconazole or fluconazole in infections of a life-threatening nature.

Acremonium

In vitro activities of polyene and imidazole antifungal agents against unusual opportunistic fungal pathogens.

Guidelines for the treatment of infections caused by unusual opportunistic fungi are limited and available in vitro data are scanty. In vitro susceptibility tests, employing an agar dilution procedure, were performed with amphotericin B (AMB), natamycin (NTC), itraconazole (ICZ), and ketoconazole (KTZ). Two media were used: Kimmig's agar (KA) and Yeast Morphology Agar (YMA). Fungi tested included isolates (n) of Acremonium spp. (10), Cunninghamella spp. (6), Fusarium spp. (18), Pseudallescheria boydii (14), and Trichosporon beigelii (5). All Acremonium and Cunninghamella isolates were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but many appeared to be resistant to AMB, (MIC greater than or equal to 32 micrograms/ml), KTZ and ICZ (MIC greater than or equal to 128 micrograms/ml). Most isolates of Fusarium spp. were susceptible to both AMB and NTC (MIC90 = 4 micrograms/ml); one isolate was cross-resistant to both polyenes (MIC greater than 32 micrograms/ml). Only two of 18 Fusarium isolates appeared susceptible to the imidazoles (MIC less than or equal to 4 micrograms/ml); the remaining isolates exhibited high MICs (greater than or equal to 64 micrograms/ml). All 14 isolates of P. boydii were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but four appeared to be resistant to AMB (MIC greater than or equal to 32 micrograms/ml). Most isolates of P. boydii were susceptible to both KTZ (MIC less than or equal to 4 micrograms/ml) and ICZ (MIC less than or equal to 16 micrograms/ml) but two isolates appeared to be resistant (MIC greater than or equal to 16 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Agents

Unusual structures of Sporothrix schenckii.

A series of environmental and clinical isolates of Sporothrix schenckii being studied in our laboratories under standard conditions of temperature, humidity and media, displayed, in some of the isolates, large dematiaceous hyphae. The large hyphae could be seen to produce the fine hyphae associated with S. schenckii on which typical microconidia developed. Typical microconidia also developed occasionally on the large hyphae, and strands of the unusually large hyphae also were seen to form arthroconidia. Some strains formed large, thin-walled cells on thin and/or thick hyphae resembling the 'balloon cells' seen in mature colonies of Trichophyton tonsurans. All strains which have demonstrated these various and unusual structures histopathologically produced typical sporotrichosis in laboratory animals. When reisolated from these animals, the cultures again exhibited the unusual structures, as well as those typical of S. schenckii.

Air Microbiology

Further in vitro studies with oxiconazole nitrate.

Oxiconazole nitrate was compared in vitro with ketoconazole and econazole nitrate in tests with 96 dermatophytes, 18 isolates of Malassezia furfur, and seven isolates of Exophiala werneckii. An agar dilution procedure was used employing either Kimmig's agar or Sabouraud's dextrose agar supplemented with Olive oil and Tween 80. Econazole was the more active compound in tests with Microsporum species (41 isolates) and most isolates of Trichophyton species (45 isolates). Oxiconazole was the more active compound in tests with T. tonsurans and T. rubrum. However, differences between results for oxiconazole and econazole and the dermatophytes were only marginal. Ketoconazole was the most active compound in tests with M. furfur; some cross resistance on the part of several isolates of M. furfur between oxiconazole and econazole was noted. All three compounds were active against E. werneckii with MIC90 values of either 0.25 or 0.5 microgram/ml. Epidermophyton floccosum was the most susceptible of all organisms tested with all MIC values for all three drugs being less than or equal to 0.063 microgram/ml, the lowest concentration tested.

Arthrodermataceae

Biochemical serogrouping of clinical isolates of Cryptococcus neoformans.

Three hundred twenty-three clinical isolates of Cryptococcus neoformans of diverse geographic origins were biochemically serogrouped using glycine-cycloheximide-phenol red agar (GCP), the same medium less cycloheximide (GOP), and glycine-L-canavanine bromothymol blue agar (CGB). Twenty isolates gave positive reactions on all three media typical of the B and C serotypes. Three were from the Peoples' Republic of China; three each were from Michigan (two patients) and Louisiana; two each were from California, Georgia, and Virginia; and one each was from Alabama, Florida, North Carolina, Oklahoma, and Tennessee. Two hundred seventy-six isolates were identified as belonging to the A/D serogroup; 272 were of American origin and four were from China. Twenty-seven isolates were biochemically ungroupable. Evaluations of the reactions on all three media were open to subjective interpretations. Utilization of glycine was the most frequent atypical variable; 36 of 276 (13%) A/D isolates utilized glycine while being inhibited by either GCP or CGB or both. Significant differences between A/D and B/C serogroups in terms of susceptibility to 5-fluorocytosine but not to amphotericin B were observed; B/C serogroup isolates appeared to be less susceptible to 5-fluorocytosine in vitro than were the A/D serogroup isolates. These results provided new evidence on the distribution of B/C serogroup isolates of C. neoformans in America and demonstrate the difficulties of using biochemical tests for serotyping purposes. They also offer a possible explanation for the apparent more refractory therapeutic responses of infections caused by B and C serotypes to conventional antifungal chemotherapy.

Amphotericin B

An overview of macrophage-fungal interactions.

A review of the literature (148 references) on the interactions of fungi with polymorphonuclear cells, monocytes and macrophages is presented. The interactions of Aspergillus species, Coccidioides immitis, Blastomyces dermatitidis, Histoplasma capsulatum, Cryptococcus neoformans, Candida albicans, and Candida species with human and experimental animal derived immune cells are examined in this overview. An effort has been made to present the reader with a comprehensive list of references with the intent of encouraging additional reading and research in this important area.

Animals

Cryptococcus neoformans: in vivo protection of mice by pretreatment with pyran copolymer.

Synthetic polyanions have been shown to alter host resistance to infection. The anticryptococcal effect of pyran copolymer was assessed in vivo and in vitro. Pretreatment with pyran copolymer significantly extended mean survival in mice lethally infected with Cryptococcus neoformans when compared to untreated animals (p less than 0.01). The anticryptococcal effect of peritoneal exudate cells (PEC) elicited by 10% thioglycollate or pyran copolymer (25 mg/kg) was assessed in vitro. Initial percent phagocytosis of both encapsulated and non-encapsulated isolates of C. neoformans was greatest in the pyran elicited PEC. Significant killing of C. neoformans in vitro was observed only in pyran-activated PEC cultures combined with non-encapsulated cells of C. neoformans, although pyran PEC did inhibit initial growth of phagocytized encapsulated yeast cells. The protection of pyran copolymer pretreated mice from infection with C. neoformans, but the absence of significant killing of encapsulated yeast in vitro suggest a complex mechanism of host defense which may involve an activation of the reticuloendothelial system by pyran copolymer.

Animals

Exoantigen test for differentiation of Exophiala jeanselmei and Wangiella dermatitidis isolates from other dematiaceous fungi.

Concentrated (25X) exoantigens of 105 isolates of pathogenic and saprophytic dematiaceous fungi and 3 isolates of Sporothrix schenckii were analyzed by the microimmunodiffusion method. The reagents used were nonadsorbed and adsorbed sera produced in New Zealand rabbits. One set of rabbits was immunized with soluble antigens of a 1-month-old culture of Exophiala jeanselmei (ATCC 34123), and the other set was immunized with soluble antigens from a culture of Wangiella dermatitidis (ATCC 28869). The reference antigens were 25X-concentrated exoantigens of the above cultures. This exoantigen test permitted the differentiation of E. jeanselmei and W. dermatitidis from one another as well as from other Exophiala species, Fonsecaea species, Phialophora species, Cladosporium species, Rhinocladiella species, and Sporothrix schenckii by presence or absence of lines of identity or of partial identity, or lines of nonidentity. Using adsorbed serum eliminated the problems with cross-reactivity seen with nonadsorbed serum. Thus, with an adsorbed serum as the reagent, it was possible to presumptively differentiate E. jeanselmei and W. dermatitidis from one another and from other dematiaceous fungi.

Antigens, Fungal

In vitro antibacterial activity of norfloxacin compared with eight other antimicrobial agents.

The antibacterial activity of norfloxacin, an organic acid structurally related to nalidixic acid, was compared with that of the oral cephalosporins cefaclor and cephalexin, and with that of nalidixic acid, cinoxacin, amikacin, ampicillin, trimethoprim alone and the combination of trimethoprim and sulfamethoxazole. Agar dilution studies were performed with a total of 398 clinical isolates of gram-negative bacteria. Norfloxacin was found to be the most active drug studied against each of the different groups of organisms tested. MIC90 values for norfloxacin were as follows: Citrobacter spp., 2 micrograms/ml; Enterobacter spp., 0.13 micrograms/ml; Escherichia coli, 0.06 micrograms/ml; Klebsiella spp., 0.13 micrograms/ml; Proteus spp., 0.06 micrograms/ml; Salmonella spp., 1 microgram/ml; Serratia spp., 0.13 micrograms/ml; and Pseudomonas spp., 2 micrograms/ml. MIC90 values for the other drugs were 4 micrograms/ml or greater and many organisms were totally resistant to one or more of the other drugs (MIC greater than 128 micrograms/ml). Cross resistance between norfloxacin and the related drugs nalidixic acid and cinoxacin was not observed.

Anti-Bacterial Agents

Immunization of mice with stable, acapsular, yeast-like mutants of Cryptococcus neoformans.

Immune responses, including lymphocyte transformation and protection, were evaluated in a new model of experimental murine cryptococcosis. Newly developed, genetically stable, acapsular mutants of Cryptococcus neoformans were used to immunize C3H/HeN mice. Intraperitoneal and subcutaneous routes of immunization without adjuvant were studied. Spleen cells and pooled popliteal and inguinal lymph node cells responded significantly to heat-killed, whole-cell C. neoformans antigen but not to Candida albicans antigen in lymphocyte transformation assays. No significant difference in lymphocyte transformation response to antigens was observed between intraperitoneally and subcutaneously immunized animals. Mean survival time of immunized mice was extended significantly in comparison to controls following intravenous challenge with virulent C. neoformans. Degree of protection was independent of route of immunization but dependent upon the magnitude of the challenge inoculum. This model should prove valuable in the study of immunoregulation of cryptococcosis and vaccine development.

Animals

Decreased virulence in stable, acapsular mutants of cryptococcus neoformans.

Six acapsular strains of Cryptococcus neoformans obtained by chemical mutagenesis failed to produce a capsule in vivo and were avirulent in mice following high dose intramuscular, intraperitoneal or intravenous inoculation. Peritoneal granulomas were observed in all animals inoculated with the acapsular mutants. These granulomas were characterized by a large central mass consisting of intact, degenerating and necrotic yeast cells. This was surrounded by concentric layers of a broad band of histiocytes, a narrow band of fibroblasts, and around the periphery, a mass of lymphocytes and plasma cells. These isolates did not revert to an encapsulated or virulent state after more than a year of subculturing or 18 passages through mice.

Animals

Immunity in cryptococcosis: an overview.

Cryptococcosis is an often fatal opportunistic fungal infection. Despite efforts to elucidate the role of immunity in host defense against the disease, much remains to be learned. The purpose of this brief review is to provide the reader with an overview of the history of research concerned with host immunity in cryptococcosis. both humoral and cell-mediated studies are included. An effort has been made to present the reader with a comprehensive list of references in the hope of encouraging additional reading and research in this important area.

Animals

Serotype B/C Cryptococcus neoformans isolated from patients in nonendemic areas.

Of 90 clinical isolates of Cryptococcus neoformans studied, 3 were determined to be serotype B/C. The patients from whom these B/C isolates were obtained were identified as never having lived in or visited the areas associated with B/C serotypes. This finding suggests a broader geographic distribution of this serotype group than previously believed. The glycine-cycloheximide-phenol red medium described by Salkin and Hurd (J. Clin. Microbiol. 15:169-171, 1982) was shown to be more accurate in differentiating A/D and B/D serotype pairs of C. neoformans than the creatinine-dextrose-bromthymol blue medium described by Kwon-Chung et al. (Int. J. Syst. Bacteriol. 28:616-620, 1978).

Cryptococcosis

Comparison of the in vitro antifungal activities of miconazole and a new imidazole, R41,400.

R41,400 is a recently synthesized, water-soluble imidazole. Its antifungal properties were compared in vitro with those of miconazole using an agar dilution procedure and 175 isolates of human fungal pathogens. The filamentous forms of Histoplasma capsulatum and Blastomyces dermatitidis were inhibited by less than or equal to 2 microgram of either drug/ml; Coccidioides immitis was inhibited by less than or equal to 0.5 microgram of R41,400/ml. Among the yeasts tested, Cryptococcus neoformans and Candida parapsilosis were the most susceptibel to the two drugs, whereas Candida albicans and Candida tropicalis were the least susceptible; 0.5 microgram of either drug/ml was inhibitory for 90%-100% of tested isolates of C. neoformans but for only less than or equal to 20% of isolates of C. albicans, C. tropicalis, and Torulopsis glabrata. Both drugs were inhibitory for most isolates of Trichophyton and Microsporum species at concentrations of less than or equal to 4 microgram/ml; Epidermophyton floccosum was uniquely susceptible to both drugs.

Antifungal Agents

In vitro studies with ambruticin, a new antifungal antibiotic.

The in vitro antifungal inhibitory activities of ambruticin and of various antifungal drugs of choice against 190 fungal pathogens representative of the major human mycoses were compared using a modification of the ICS agar dilution technique. Ambruticin compared favorably with amphotericin B and miconazole when tested against the dimorphic pathogens Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis and against Aspergillus fumigatus. Miconazole was the most active compound against Sporothrix schenckii, Allescheria (Petriellidium) boydii, and selected dematiaceous fungi, with ambruticin giving minimal inhibitory, concentrations from 3- to 74-fold higher. Ambruticin compared unfavorably with amphotericin B and 5-fluorocytosine when tested against Candida and Torulopsis species. Ambruticin was not as active in vitro as tolnaftate when tested against the three genera of dermatophytic fungi, but compared favorably with miconazole.

Antifungal Agents

In vitro comparison of the antifungal activities of R34,000, miconazole and amphotericin B.

In vitro susceptibilities of 78 isolates of pathogenic filamentous fungi to the imidazole compounds R34,000 and miconazole and to amphotericin B were determined using an agar dilution technique. Allescheria boydii, Sporothrix schenckii and the dematiaceous fungi (Cladosporium, Fonsecaea and Phialophora spp.) were most susceptible to miconazole with minimum inhibitory concentration (MIC) values ranging from less than or equal to 0.25 to 32 microgram/ml and with geometric mean MIC (G-MIC) values of 0.56-1.24 microgram/ml. Isolates of Aspergillus fumigatus were more susceptible to amphotericin B and miconazole than to R34,000 with G-MIC values of 1.20 and 3.48 microgram/ml, respectively. Coccidioides immitis, Histoplasma capsulatum and Blastomyces dermatitidis were highly susceptible to all three drugs (G-MICs greater than 1 microgram/ml); R34,000 was the most active of the three compounds against C. immitis (G-MIC = 0.44 microgram/ml).

Amphotericin B