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Biomedical subjects

M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Fatal cerebral mycoses caused by the ascomycete Chaetomium strumarium.

Three cases of fatal cerebral mycosis in males with prior histories of intravenous drug use from the United States and Australia are reported. Infection in each case was limited to brain abscess; no other sites of infection were observed. The fungus seen by histopathology and isolated from the brain tissue in each case was identified as Chaetomium strumarium. This is the first report of human infection by this species, and C. strumarium is the second species of Chaetomium known to cause primary brain infection. Chaetomium strumarium is unusual among members of the genus Chaetomium in forming ascocarps covered with pale, thin-walled, flexuous hairs, a feature leading to its original placement in the genus Achaetomium. Presence of pinkish exudate droplets and/or crystals associated with hyphae or ascocarps, sometimes accompanied by a pinkish diffusible pigment; good growth at 42 degrees C; and production of small conidia further distinguish this species. The brain abscess isolates were compared with isolates from prior cases of cerebral infection which had been identified as either Chaetomium atrobrunneum or Chaetomium globosum. With reidentification of one isolate originally identified as C. globosum to C. atrobrunneum, only C. strumarium and C. atrobrunneum have been confirmed to cause infection involving the brain.

Adult↗
PubMed1995

Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for azole antifungal susceptibility testing.

The use of Etest strips for antimicrobial susceptibility testing is a new and promising method with broad applications in microbiology. Since these strips contain a predefined continuous gradient of a drug, it is possible to obtain a reproducible, quantitative MIC reading. We performed a prospective and double-blinded study to compare the Etest and National Committee for Clinical Laboratory Standards (Villanova, Pa.) broth macrodilution methods for determining the MICs of fluconazole, itraconazole, and ketoconazole for 100 clinical isolates (25 Candida albicans, 25 Cryptococcus neoformans var. neoformans, 20 Torulopsis [Candida] glabrata, 15 Candida tropicalis, and 15 Candida parapsilosis). The Etest method was performed according to the manufacturer's instructions, and the reference method was performed according to National Committee for Clinical Laboratory Standards document M27-P guidelines. Despite differences between results for some species-drug combinations, Etest and macrobroth MICs were, in general, in good agreement. The MIC agreement rates for the two methods, within +/- 1 dilution, were 71% for ketoconazole, 80% for fluconazole, and 84% for itraconazole. According to our data, Etest has potential utility as an alternative method.

Antifungal Agents↗
PubMed1995

Disseminated Microascus cirrosus infection in pediatric bone marrow transplant recipient.

Microascus cirrosus Curzi and its associated anamorphic state, Scopulariopsis, were recovered from the cutaneous lesion of a 12-year-old male who had undergone an autologous bone marrow transplantation for acute myelogenous leukemia. Histopathology sections from the biopsied lesion demonstrated septate hyphae consistent with a fungal etiology. Radiographic studies of the lungs subsequent to progression of the lesion revealed a consolidation in the right upper lobe suggesting a primary focus of infection. While M. cirrosus is fairly abundant in nature and widely distributed in stored grains in North America, this is, to our knowledge, the first reported human infection by this species. Salient characteristics for the identification of this dematiaceous ascomycete, M. cirrosus, will be presented.

Ascomycota↗
PubMed1995

Quality control guidelines for National Committee for Clinical Laboratory Standards recommended broth macrodilution testing of amphotericin B, fluconazole, and flucytosine.

Amphotericin B, fluconazole, and flucytosine (5FC) were tested in a multilaboratory study to establish quality control (QC) guidelines for yeast antifungal susceptibility testing. Ten candidate QC strains were tested in accordance with National Committee for Clinical Laboratory Standards M27-P guidelines against the three antifungal agents in each of six laboratories. Each laboratory was assigned a unique lot of RPMI 1640 broth medium as well as a lot of RPMI 1640 common to all of the laboratories. The candidate QC strains were tested 20 times each against the three antifungal agents in both unique and common lots of RPMI 1640. A minimum of 220 MICs per drug per organism were generated during the study. Overall, 95% of the MICs of amphotericin B, fluconazole, and 5FC fell within the desired 3 log2-dilution range (mode +/- 1 log2 dilution). Excellent performance with all three drugs was observed for Candida parapsilosis ATCC 22019 and C. krusei ATCC 6258. With these strains, on-scale 3 log2-dilution ranges encompassing 96 to 99% of the MICs of all three drugs were established. These two strains are recommended for QC testing of amphotericin B, fluconazole, and 5FC. Reference ranges were also established for an additional four strains for use in method development and for training. Four strains failed to perform adequately for recommendation as either QC or reference strains.

Amphotericin B↗
PubMed1995

Three distinct genotypes within Candida parapsilosis from clinical sources.

Three genetically distinct groups of Candida parapsilosis were detected among clinical isolates. These were distinguishable on the basis of isoenzyme profiles and DNA sequences of internally transcribed spacer (ITS) sequences flanking the 5.8S RNA gene. In an investigation of 45 strains, including 32 clinical isolates from Texas, C. parapsilosis group I composed the majority of the common clinical isolates. The type strain of C. parapsilosis was a member of this group. The 10 group II isolates were indistinguishable from group I strains when tested with the API 20C kit. The two group III isolates differed from those in groups I and II by being D-xylitol positive by the API 20C kit; however, isolates in all groups assimilated D-xylitol from broth. Isoenzyme profiles excluded the close relationship of any of these groups to Lodderomyces elongisporus, which is a teleomorphic yeast that has a physiological profile similar to that of C. parapsilosis. Although there were insignificant differences in the ITS2 rDNA sequences, comparisons of the ITS1 sequences revealed several differences. A sequence analysis of ITS1 in which missing bases were counted as mismatches showed the following similarities: group I versus group II, 87.7%; group I versus group III, 82.1%; group II versus group III, 84.5%. Also, the activity of secreted proteinase showed differences among the three groups, with many group I isolates having moderate to high activity. The degree of susceptibility to antifungal agents, amphotericin B, ketoconazole, and 5-fluorocytosine, could not be used to determine an isolate's group.

Antifungal Agents↗
PubMed1995

Continuous ambulatory peritoneal dialysis complicated by Aureobasidium pullulans peritonitis.

We describe a case of peritonitis caused by Aureobasidium pullulans in a patient on continuous ambulatory peritoneal dialysis (CAPD). This dematiaceous fungus rarely causes infection in humans and to date has not been reported as an etiology of CAPD-associated peritonitis. The patient was managed successfully with peritoneal catheter removal and a prolonged course of intravenous amphotericin B, allowing resumption of CAPD. In vitro susceptibility testing confirmed sensitivity of this organism to amphotericin B.

Adult↗
PubMed1994

Discrepancies between MIC and MLC values of amphotericin B against isolates of Aspergillus species.

There is little information addressing the phenomena of discrepancy between minimal inhibitory concentrations (MIC) and minimal lethal concentrations (MLC) values of amphotericin B (AMB) to clinical isolates of fungi. This study assessed in vitro activity of AMB against 70 clinical isolates of aspergilli: 30 strains of Aspergillus fumigatus, 20 strains of Aspergillus flavus and 20 strains of Aspergillus niger. Susceptibility tests were accomplished using a macro broth dilution procedure, with special emphasis on ascertainment of MLCs. AMB exhibited low MIC values against all clinical isolates. While we did not identify any AMB resistant isolates among 70 Aspergillus spp. studied as judged by MIC levels, analysis of the data demonstrated a clear discrepancy between the MIC and MLC levels of AMB obtained against clinical isolates of Aspergillus spp. The MLC values of AMB were significantly higher than the MIC values with MIC 50 and MIC 90 of 0.29 and 0.5 microgram/ml, respectively, at the second reading time, and MLC 50 and MLC 90 of 2.31 and 9.24 micrograms/ml, respectively (p < 0.001). Additionally, minimal lethal concentrations in 36/70 (51%) of aspergillal isolates studied produced drug concentrations above those which can usually be sustained in patient plasma or tissue.

Amphotericin B↗
PubMed1994

Multicenter comparison of a colorimetric microdilution broth method with the reference macrodilution method for in vitro susceptibility testing of yeast isolates.

This multicenter study was performed to compare a colorimetric microdilution method with the NCCLS M27-P reference macrodilution method for the testing of yeast isolates against amphotericin B, fluconazole, and 5-fluorocytosine (5FC). Testing was performed on ten yeast isolates in five independent laboratories. All sites tested each isolate a total of 20 times with both methods. MICs were read after 48 h incubation. The macrodilution MIC reference range was defined as the modal MIC +/- 1-log2 dilution for each organism-antifungal agent combination. Agreement between the M27-P reference range results and the microdilution MICs was 86% with amphotericin B, 90% with fluconazole, and 93% with 5FC. Based on these data, it is apparent that new approaches, such as the colorimetric microdilution method, will provide MIC values comparable to the M27-P macrodilution method in a format that is more practical for use in a busy clinical laboratory.

Amphotericin B↗
PubMed1994

Treatment of coccidioidomycosis with SCH 39304.

A new oral triazole antifungal, SCH 39304, was administered to 54 patients with progressive infections due to Coccidioides immitis from six collaborating centers. Patients were grouped according to site of infection including chronic pulmonary (25), bone/joint (17) and skin/soft tissue (12). The median age was 40 years; 83% were male, 52% white, 13% HIV-infected and 35% had failed previous therapy. The majority of patients were treated with either 100 mg or 200 mg day-1. One patient on renal dialysis received 300 mg day-1. Baseline abnormalities were reassessed for evidence of efficacy every 4 months and expressed in a standardized scoring system. Cumulative overall response rates at 4, 8 and 12 months were 7%, 36% and 66% respectively. Twelve month response rates by disease were 77% (pulmonary), 62% (skin/soft tissue) and 31% (bone/joint). Fifteen patients failed therapy although seven of these were still on treatment when the study was discontinued. Two failed due to toxicity. Possible symptoms or signs of toxicity occurred in 24 (44%) patients and were generally mild. SCH 39304 is an effective and well tolerated therapy for progressive forms of coccidioidomycosis.

Administration, Oral↗
PubMed1994

Fungemia and colonization with nystatin-resistant Candida rugosa in a burn unit.

Yeast isolates from burned patients were analyzed retrospectively for a 7-year period (1984-1991). Topical nystatin was used routinely in the burn wound dressing as antifungal therapy beginning in July 1986. Nystatin used was associated with a significant decrease in overall yeast acquisitions in burn wounds; yeasts were isolated from 15.5% of admitted patients before the use of nystatin vs. 10.5% with use of nystatin (odds ratio [OR] = 0.64; 95% confidence interval [CI], 0.48-0.86). New acquisitions of Candida rugosa in burn wounds increased from 0.36% of admissions during the period July 1984 to June 1986 (before nystatin use) to 5.25% in the period July 1986 to June 1991 (during use of nystatin) (OR = 15.3; 95% CI, 4.1-128). The incidence of fungemia decreased from 3.25% of admissions in the pre-nystatin period to 1.43% in the postnystatin period (OR = 0.43; 95% CI, 0.22-0.87). C. rugosa caused none of 18 fungemias in the former period and 15 of 21 in the latter period (P = .002). Susceptibility testing of recent C. rugosa isolates demonstrated resistance to nystatin and moderate susceptibility to amphotericin B and fluconazole. Topical nystatin use was associated with a decrease in fungemias and acquisition of yeasts in burn wounds but with an increase in colonization and fungemias caused by nystatin-resistant, amphotericin B-susceptible C. rugosa.

Amphotericin B↗
PubMed1994

Zygomycosis due to Mucor circinelloides in a neutropenic patient receiving chemotherapy for acute myelogenous leukemia.

Mucor circinelloides form circinelloides has rarely been associated with human disease, even in immunocompromised patients. We report a case of cutaneous zygomycosis caused by M. circinelloides in a 23-year-old neutropenic woman receiving consolidation chemotherapy for acute myelogenous leukemia. The organism was exquisitely susceptible to amphotericin B. Despite the fact that the patient was profoundly neutropenic for an additional 3 weeks, the lesions began to resolve during therapy, and no surgical debridement was required.

Adult↗
PubMed1994

Clinically significant mucosal candidiasis resistant to fluconazole treatment in patients with AIDS.

Eight cases of severe mucosal candidiasis in patients with AIDS who were taking fluconazole at a dosage of 400-800 mg/d are described. Candida albicans alone or in conjunction with Torulopsis glabrata or Candida stellatoidea was isolated from each patient. In vitro susceptibility testing demonstrated resistance to fluconazole in all eight cases. All tested isolates were susceptible to amphotericin B, and six of eight isolates tested were susceptible to itraconazole. All individuals were severely immunocompromised (CD4 lymphocyte counts: mean, 15/mm3; range, 6-39/mm3) and had been receiving prophylaxis with fluconazole for a mean of only 3 months (range, 1-7 months). The occurrence of candidal mucositis in patients receiving high doses of fluconazole is a matter of concern that requires further study in regard to the causes, prevention, and treatment of the disease.

AIDS-Related Opportunistic Infections↗
PubMed1994

In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus.

We investigated the in vitro activity of a new antifungal triazole, D0870, against 100 Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus by using a broth macrodilution method following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P). All of the isolates were chosen from C. albicans isolates already tested for fluconazole susceptibility by the procedure of the National Committee for Clinical Laboratory Standards. Fifty isolates were considered fluconazole susceptible (MICs, < or = 4 micrograms/ml), and 50 isolates were considered fluconazole resistant (MICs, > or = 8 micrograms/ml). The in vitro data demonstrated that D0870 had good activity against isolates tested; for 90% of all strains of C. albicans, MICs were 0.5 micrograms/ml. However, the D0870 MICs for the fluconazole-susceptible isolates were lower than those for the fluconazole-resistant isolates; MICs for 50 and 90% of the isolates tested were < or = 0.0078 and 0.06 micrograms/ml, respectively, for fluconazole-susceptible isolates and 0.25 and 2 micrograms/ml, respectively, for fluconazole-resistant isolates (P < 0.001). Our data suggest that this new triazole could represent a valid alternative in the treatment of oral candidiasis in human immunodeficiency virus-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma.

Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls. At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log10 CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 micrograms/ml; range, < 0.5 to 16.8 micrograms/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A. fumigatus. This model demonstrated that levels in plasma of greater than 6 micrograms/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 micrograms/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis.

Amphotericin B↗
PubMed1994

In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus.

A broth macrodilution technique, which was performed by following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P), was applied to study the in vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from the oral cavities of 100 patients infected with human immunodeficiency virus. The in vitro data demonstrated that itraconazole had good activity against the tested isolates; for 90% of all strains of C. albicans, MICs were 1 microgram/ml, and only one isolate was highly resistant to this triazole (MIC, > 16 micrograms/ml). However, the itraconazole MICs for the fluconazole-susceptible isolates were significantly lower than those for the fluconazole-resistant isolates; the MICs for 50 and 90% of the isolates tested were < or = 0.03 and 0.25 microgram/ml, respectively, for the fluconazole-susceptible isolates and 0.5 and 1 microgram/ml, respectively, for the fluconazole-resistant isolates (P = 0.00001). Our findings could be of clinical relevance because human immunodeficiency virus-infected patients who fail fluconazole therapy for oral and/or esophageal candidiasis may require itraconazole at doses higher than those used in standard therapy.

Candida albicans↗