Cryptococcosis and the basidiospore.
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Basidiomycota↗
Biomedical subjects
J R Perfect
Publications and source records attributed to J R Perfect.
Treatment of experimental cryptococcal meningitis with amphotericin B, 5-fluorocytosine, and ketoconazole.
Ketoconazole, amphotericin B, 5-fluorocytosine, and combinations of these drugs were compared as therapy for chronic cryptococcal meningitis in steroid-treated rabbits. Two hours after treatment of rabbits with meningitis with single drugs the mean cerebrospinal fluid concentration of 5-fluorocytosine was 4.4 microgram/ml, that of amphotericin B was less than 0.3 microgram/ml, and that of ketoconazole ranged from less than 0.2 to 0.8 microgram/ml. Serial quantitative cultures indicated that amphotericin B was the best single-drug regimen. Ketoconazole provided little or no additive effect when used in combination with fluorocytosine or therapeutic doses of amphotericin for two weeks. However, the combination of ketoconazole plus amphotericin B was at least as effective as amphotericin B plus 5-fluorocytosine over a two-week treatment regimen. The addition of ketoconazole to subtherapeutic dose of amphotericin B significantly increased the killing of cryptococci in cerebrospinal fluid.
Amphotericin B↗
Method for the purification of Filobasidiella neoformans basidiospores by flow cytometry.
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Cryptococcus↗
Leukocyte subpopulations in cerebrospinal fluid of normal rabbits.
Cerebrospinal fluid leukocytes from 48 apparently healthy New Zealand white rabbits were examined to define the number and types of cells present. The cerebrospinal fluid contained 0 to 7 leukocytes/mm3 (median 3/mm3). This small pool of mononuclear cells was comprised of 40 to 79% lymphocytes (median 67%) and 21 to 60% monocytes (median 33%). T lymphocytes were the predominant cell type, outnumbering B cells by approximately 100 to 1. In contrast to cerebrospinal fluid, normal rabbit blood contained nearly equal proportions of B and T cells (median 39% and 46% of lymphocytes, respectively). Three cerebrospinal fluid samples from apparently healthy rabbits had greater than 20 leukocytes/mm3.
Animals↗
Pharmacokinetics of cefoperazone, moxalactam, cefotaxime, trimethoprim and sulphamethoxazole in experimental meningitis.
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Animals↗
Potential value of cefoperazone in bacterial meningitis: experimental studies.
To assess the potential value of cefoperazone in treating bacterial meningitis, its pharmacokinetics in the cerebrospinal fluid of rabbits were studied. Cefoperazone penetrated poorly into the cerebrospinal fluid of rabbits with uninflamed meninges, but in the presence of meningitis concentrations increased 2- to 3-fold. These concentrations were above the minimum inhibitory concentrations for the majority of Enterobacteriaceae, indicating the potential value of cefoperazone in treating bacterial meningitis. The half-lives of cefoperazone and moxalactam in cerebrospinal fluid, measured by a bioassay, were marked prolonged by meningeal inflammation. In contrast, the half-life of cefotaxime in cerebrospinal fluid was short. Consequently both cefoperazone and moxalactam provided significantly better antibacterial effect in cerebrospinal fluid than did cefotaxime.
Animals↗
Influence of agglutinating antibody in experimental cryptococcal meningitis.
A model for chronic Cryptococcus neoformans meningitis in corticosteroid-treated rabbits was used to determine the influence of pre-formed agglutinating antibody to cryptococcal polysaccharide on the progress of this infection. Immunized rabbits developed serum agglutinating antibody with a geometric mean titre of 1:32, but none was detected in cerebrospinal fluid. Prior immunization did not enhance immunity to infection, had no effect on the number of viable cryptococci in cerebrospinal fluid, and did not prevent dissemination outside the central nervous system. Future investigations in this field should focus on cellular rather than humoral defence mechanisms.
Agglutinins↗
Mediastinitis complicating cellulitis of the head and neck.
A patient with mediastinitis caused by Streptococcus pyogenes and/or Staphylococcus aureus responded to antibiotic therapy without surgical intervention, although fever was prolonged and recovery slow. The medical and surgical management of mediastinitis is discussed.
Cellulitis↗
Comparison of cotrimoxazole, ampicillin, and chloramphenicol in treatment of experimental Haemophilus influenzae type B meningitis.
To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of infected rabbits, reaching 40 and 26%, respectively, of their simultaneous serum levels. Levels measured 30 and 60 min after intravenous injection exceeded the minimum inhibitory concentration of this combination for H. influenzae by 10- to 100-fold. The mean ratio of trimethoprim to sulfamethoxazole in cerebrospinal fluid was 1:22. Cotrimoxazole was as effective as ampicillin in therapy of beta-lactamase-negative H. influenzae meningitis and as effective as chloramphenicol for a beta-lactamase positive strain. These findings corroborate favorable preliminary clinical experience reported by others and indicate that cotrimoxazole deserves further study in the therapy of bacterial meningitis.
Ampicillin↗
Chronic cryptococcal meningitis: a new experimental model in rabbits.
This paper describes the salient features of a new model for chronic cryptococcal meningitis in cortisone-treated rabbits. Normal rabbits soon recovered after intracisternal inoculation of Cryptococcus neoformans, but cortisone-treated animals developed chronic progressive meningitis that was fatal in 2-12 weeks. Incidence and severity of infection was related to cortisone dose, not to inoculum size. The number of mononuclear cells that migrated into the subarachnoid spaces and cerebrospinal fluid of infected rabbits was strikingly reduced by cortisone treatment. Rabbits with cryptococcal meningitis were febrile; their high body temperature did not confer resistance to this infection. Cortisone-treated rabbits provide a new and expedient laboratory model for cryptococcal disease. Potential applications include study of the pathogenesis of cryptococcosis, investigation of the immunobiology of the CNS in chronic meningitis, and in vivo evaluation of newer anticryptococcal treatment regimens.
Adult↗
The actin gene from Cryptococcus neoformans: structure and phylogenetic analysis.
Using heterologous probing of a genomic library, we have cloned and sequenced the actin gene from the pathogenic yeast Cryptococcus neoformans. The actin gene is 1371 bp in length, and exists as a single copy, as is the case for all fungi studied to date. The locations of the introns in the C. neoformans actin gene are unique among all other known actin genes, and the deduced coding sequence results in a 375 amino acid chain with very high homology to other actins. A phylogenetic tree comprising 31 actin-coding sequences from a wide variety of organisms shows that the C. neoformans actin gene is grouped on a distinct branch together with all other known fungal actin sequences. The availability of the C. neoformans actin gene will aid future phylogenetic and molecular studies of this important human pathogen.
Actins↗
Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review.
Actinobacillus actinomycetemcomitans is a small fastidious gram-negative coccobacillus that fails to grow on MacConkey's agar. Slow growth in broth may lead to delays in diagnosis. First described in 1912, A. actinomycetemcomitans has been recognized since 1962 as capable of causing serious infections in humans. Such infections include periodontal infection, soft tissue abscess (often in association with Actinomyces species), and systemic infection, most commonly endocarditis. Fifteen cases and a review of the English-language literature are presented to define the epidemiology and clinical features of infection due to A. actinomycetemcomitans. Therapy for infection due to A. actinomycetemcomitans has most commonly involved ampicillin or penicillin, often in conjunction with an aminoglycoside. However, resistance to penicillin or ampicillin is common. Antimicrobial agents with a high degree of in vitro activity included cefazolin, cefotaxime, cetriaxone, aminoglycosides, and chloramphenicol. Therapy should be guided by clinical response and in vitro susceptibility testing.
Actinobacillus Infections↗
Infection and cyclosporine.
Cyclosporine is a potent immunosuppressive agent that selectively impairs T cell function. The steady growth of its importance makes knowledge of its activity and effects clinically relevant. The intrinsic antibiotic activity of cyclosporine is limited; although it inhibits certain viruses, fungi, protozoa, and helminths, in practical terms these effects are insignificant. Both controlled and noncontrolled studies have shown that infection is an infrequent problem in patients with autoimmune diseases who are receiving relatively low doses. The use of cyclosporine in the setting of transplantation does not increase--and may in fact decrease--the incidence of infection in comparison with that during standard immunosuppressive therapy. Fungal, viral, and bacterial diseases remain a risk, however, and are a significant cause of morbidity in this population. Antimicrobial therapy may alter cyclosporine levels and cause nephrotoxicity or graft rejection. Careful monitoring of cyclosporine levels during antimicrobial treatment is therefore recommended.
Animals↗
Disseminated zygomycosis: report of four cases and review.
We present four cases of disseminated zygomycosis that illustrate the characteristic clinical syndromes and natural history of this infection. The zygomycetes affect individuals immunosuppressed by age, drug therapy, or underlying disease. A previous splenectomy or deferoxamine therapy may be an additional factor in the development of disseminated zygomycosis. Clinical syndromes reflect vascular invasion and organ infarction. Diagnosis requires consideration of risk factors followed by biopsy of the affected organ for culture and for demonstration of broad nonseptate hyphae in tissue sections. Despite advances in the management of many bacterial and fungal infections in the immunosuppressed host, the results of therapy for disseminated zygomycosis remain dismal.
Adult↗
Fluconazole therapy for experimental cryptococcosis and candidiasis in the rabbit.
Fluconazole is a second-generation azole compound with broad-spectrum antifungal activity. It has been examined in several animal models emphasizing important clinical sites of infection with common yeast pathogens. The drug has an excellent pharmacokinetic profile for central nervous system, renal, and ocular infections; at these sites fluconazole has been successful in the treatment of infections with Cryptococcus neoformans or Candida albicans. On the basis of the experience in animals, fluconazole should be critically evaluated in the treatment of human mycoses such as cryptococcosis of the central nervous system and renal/ocular candidiasis. This agent represents the new wave of interest in the increasingly troublesome problem of deep-seated fungal infections.
Animals↗
The use of amphotericin B in nosocomial fungal infection.
The use of potent broad-spectrum antibacterial agents, the increasing number of immunocompromised hosts, and the use of invasive treatment modalities have exacerbated the problems involved in the management of nosocomial fungal infection. The hospital records at a tertiary-care medical center were retrospectively reviewed in an effort to determine the magnitude of these problems. A plethora of fungal species were isolated from patients. Hospital infection surveillance revealed between 30 and 40 nosocomial yeast infections per month, with 20% of nosocomial urinary tract infections caused by yeasts rather than by bacterial pathogens and one or two cases of fungemia per week. Although these figures represent a large number of nosocomial fungal infections, a significant increase in the number of such infections over the last several years could not be documented. The use of amphotericin B was found to have increased each year. The patterns of use of amphotericin B changed little between 1983 and 1987, but the number of patients treated with this agent increased dramatically.
Administration, Intravesical↗
Trimethoprim-sulfamethoxazole vs. ampicillin in the treatment of experimental meningitis due to Streptococcus pneumoniae.
When given in combination, both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis, reaching concentrations that should have been adequate for synergistic killing of Streptococcus pneumoniae. However, trimethoprim-sulfamethoxazole was less effective than ampicillin in the treatment of this experimental infection. The effect of the combination on pneumococci in vivo was bacteriostatic rather than bactericidal, possibly because the number of pneumococci in the cerebrospinal fluid of the rabbits at the start of treatment was larger than that in the inoculum used for in vitro sensitivity tests.
Ampicillin↗
Combined therapy with amphotericin B and 5-fluorocytosine for Candida meningitis.
The course and outcome of combined treatment with amphotericin B and 5-fluorocytosine were analyzed in 17 patients with candida meningitis. Eleven patients were twelve months of age or younger; seven of these were neonates. All but two patients had underlying conditions or therapy that could predispose them to systemic candidiasis. The median duration of concurrent dual therapy was 26 days; in ten cases, therapy with either drug alone was continued longer. Fifteen patients improved; 14 were cured of their infection. Cultures of cerebrospinal fluid became sterile a median of seven days after the start of therapy. Primary resistance to 5-fluorocytosine was found in four of the Candida isolates, and acquired resistance, in one. Serious adverse drug reactions were uncommon. The two patients who died had received intrathecal rather than systemic amphotericin B. One of eight infants who survived had psychomotor retardation; three of eleven infants developed hydrocephalus. Although experience with candida meningitis is limited, the combination of amphotericin B and 5-fluorocytosine is effective and offers potential advantages over amphotericin B alone.
Adult↗