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M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 163 records · Page 9Linked to original sources

Variations in fluconazole susceptibility and electrophoretic karyotype among oral isolates of Candida albicans from patients with AIDS and oral candidiasis.

DNA subtyping by pulsed-field gel electrophoresis and in vitro susceptibility testing were used to study strain variation and fluconazole resistance in Candida albicans isolates from patients with AIDS undergoing azole (fluconazole and clotrimazole) therapy for oropharyngeal candidiasis. A total of 29 patients suffered 71 episodes of oropharyngeal candidiasis. Overall, 121 isolates of C. albicans recovered throughout the course of treatment of each infection were available for further characterization. DNA subtyping revealed a total of 61 different DNA subtypes. In vitro susceptibility testing of the 121 isolates by using proposed standard methods of the National Committee for Clinical Laboratory Standards revealed MICs of fluconazole ranging from < or = 0.125 to > 64 micrograms/ml. The MIC for 50% of isolates tested was 0.25 microgram/ml, and the MIC for 90% of isolates tested was 8.0 micrograms/ml. MICs were > or = 64 micrograms/ml for only 7.4% of the isolates tested. The majority (62%) of the patients with oropharyngeal candidiasis and undergoing azole therapy were infected or colonized with more than one DNA subtype, and the introduction or selection of strains with a more resistant DNA subtype during the course of fluconazole therapy was not uncommon. With one exception, this did not appear to have an adverse effect on clinical outcome. In contrast, for patients with AIDS and oropharyngeal candidiasis infected with a single DNA subtype of C. albicans, an increase in fluconazole MICs for the infecting strain was rarely demonstrated over the course of therapy.

Acquired Immunodeficiency Syndrome↗

Comparative study of broth macrodilution and microdilution techniques for in vitro antifungal susceptibility testing of yeasts by using the National Committee for Clinical Laboratory Standards' proposed standard.

A comparative study of broth macro- and microdilution methods for susceptibility testing of fluconazole, itraconazole, flucytosine, and amphotericin B was conducted with 273 yeasts. The clinical isolates included 100 Candida albicans, 28 Candida tropicalis, 25 Candida parapsilosis, 15 Candida lusitaniae, 15 Candida krusei, 50 Cryptococcus neoformans var. neoformans, 25 Torulopsis (Candida) glabrata, and 15 Trichosporon beigelii strains. Both methods were performed according to the National Committee for Clinical Laboratory Standards' (NCCLS) recommendations (document M27-P). For fluconazole, itraconazole, and flucytosine, the endpoint was the tube that showed 80% growth inhibition compared with the growth control for the macrodilution method and the well with slightly hazy turbidity (score 1) compared with the growth control for the microdilution method. For amphotericin B, the endpoint was the tube and/or well in which there was absence of growth. For the reference macrodilution method, the MICs were determined after 48 h of incubation for Candida spp., T. glabrata, and T. beigelii and after 72 h for C. neoformans var. neoformans. For the microdilution method, either the first-day MICs (24 h for all isolates other than C. neoformans and 48 h for C. neoformans var. neoformans) or the second-day MICs (48 and 72 h, respectively) were evaluated. The agreement within one doubling dilution of the macrodilution reference for all drugs was higher with the second-day MICs than with the first-day MICs for the microdilution test for most of the tested strains. General agreement was 92% for fluconazole, 85.7% for itraconazole, 98.3% for flucytosine, and 96.4% for amphotericin B. For C. neoformans var. neoformans and T. beigelii, the agreement of the first-day reading was higher than that of the second-day reading for fluconazole (94 versus 92%, respectively, for C. neoformans var. neoformans, and 86.7 versus 80%, respectively, for T. beigelii). Our studies indicate that the microdilution technique performed following the NCCLS guidelines with a second-day reading is a valid alternative method for testing fluconazole, itraconazole, flucytosine, and amphotericin B against these eight species of yeasts.

Drug Resistance, Microbial↗

Multisite reproducibility of colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates.

MICs of fluconazole and amphotericin B were determined independently for 100 coded yeast isolates by each of six laboratories to determine reproducibility of results by using a colorimetric oxidation-reduction-based broth microdilution test. In addition, each site tested five quality control isolates on at least four different occasions during the study. Results agreed within a three-dilution range (mode +/- 1 log2 dilution) for 96.2% of fluconazole tests and 92.7% of amphotericin B tests. Agreement among tests with the quality control isolates was 99.4% with fluconazole and 98.6% with amphotericin B. These results indicate that the colorimetric microdilution method is reproducible among laboratories.

Amphotericin B↗

Selection of candidate quality control isolates and tentative quality control ranges for in vitro susceptibility testing of yeast isolates by National Committee for Clinical Laboratory Standards proposed standard methods.

The National Committee for Clinical Laboratory Standards has developed a proposed standard method for in vitro antifungal susceptibility testing of yeast isolates (National Committee for Clinical Laboratory Standards, document M27-P, 1992). In order for antifungal testing by the M27-P method to be accepted, reliable quality control (QC) performance criteria must be developed. In the present study, five laboratories tested 10 candidate QC strains 20 times each against three antifungal agents: amphotericin B, fluconazole, and 5-fluorocytosine. All sites conformed to the M27-P standards and used a common lot of tube dilution reagents and RPMI 1640 broth medium. Overall, 98% of MIC results with amphotericin B, 95% with fluconazole, and 92% with 5-fluorocytosine fell within the desired 3-log2 dilution range (mode +/- 1 log2 dilution). Excellent performance with all three antifungal agents was observed for six strains: Candida albicans ATCC 90028, Candida parapsilosis ATCC 90018, C. parapsilosis ATCC 22019, Candida krusei ATCC 6258, Candida tropicalis ATCC 750, and Saccharomyces cerevisiae ATCC 9763. With these strains, 3-log2 dilution ranges encompassing 94 to 100% of MICs for all three drugs were established. Additional studies with multiple lots of RPMI 1640 test medium will be required to establish definitive QC ranges.

Amphotericin B↗

Candida lusitaniae osteomyelitis in a premature infant.

Candida lusitaniae is emerging as an opportunistic pathogen in premature infants. Treatment of C. lusitaniae is challenging due to frequent resistance of this organism to antifungal agents and lack of standardized susceptibility testing for fungi. We report the case of a premature infant with C. lusitaniae osteomyelitis in whom treatment was successful with 5-fluorocytosine and fluconazole.

Candidiasis↗

Uncommon invasive fungal pathogens in the acquired immunodeficiency syndrome.

This communication lists fungi reported to cause invasive infection in patients with AIDS. It excludes the well known and common fungi that infect these patients such as Candida, Cryptococcus, Histoplasma, Coccidioides and Aspergillus. It is likely that these less common fungal pathogens will be seen more frequently in the enlarging AIDS population as it is continuously exposed to many of these potentially opportunistic fungi.

AIDS-Related Opportunistic Infections↗

Invasive infection due to Apophysomyces elegans in immunocompetent hosts.

A previously well 59-year-old man developed necrotizing, invasive cellulitis and subsequent osteomyelitis at what was judged to be the site of a bite or sting. The pathogen isolated was Apophysomyces elegans. Eventually, in addition to treatment with intravenous amphotericin B, en bloc resection was required for cure. Only six previous cases of A. elegans infection have been reported in the literature. The lack of underlying disease in six of the total of seven cases contrasts with the usual findings for other zygomycoses. This article describes all seven reported cases as well as the characteristics of this unique fungal pathogen.

Amphotericin B↗

Fluconazole-resistant Candida albicans.

Mucocutaneous candidiasis caused by Candida albicans is a common complication of human immunodeficiency virus (HIV) infection. Recent reports of isolation of resistant strains of C. albicans raise the specter of more widespread resistance, but limited series are available to analyze situations in which the likelihood of resistance is greatest. We present our experience with fluconazole-resistant candidiasis in patients with HIV infection obtained from retrospective chart review and by testing strains of C. albicans isolated during relapse for susceptibility to antifungal agents. The possible reasons for failure of antifungal therapy are discussed, as well the correlation between in vivo and in vitro data. Resistant candidiasis in patients with HIV disease is an emerging problem of considerable concern that merits further study.

AIDS-Related Opportunistic Infections↗

Correlation of in vitro azole susceptibility with in vivo response in a murine model of cryptococcal meningitis.

Correlations between in vitro susceptibility and in vivo responses to fluconazole were sought in a mouse model of cryptococcal meningitis. Twenty clinical isolates were used. Two distinct populations were noted. Eight high-virulence isolates had an LD50 of < or = 252 cfu of Cryptococcus neoformans. Twelve low-virulence isolates had an LD50 of > 252 cfu. For 7 low-virulence isolates, the LD50 was > 20,000 cfu. C. neoformans also had a broad range of in vitro susceptibilities (MICs of 1.25 to > 80 micrograms/mL) at 24 h. A correlation was found between the MIC and the minimum effective dose of fluconazole in mice. This was observed with both survival and tissue counts as parameters of efficacy. This study documents for the first time the in vivo relevance of in vitro susceptibility to an azole antifungal for C. neoformans.

Acquired Immunodeficiency Syndrome↗

Efficacy of itraconazole solution in a rabbit model of invasive aspergillosis.

The efficacy of an itraconazole-cyclodextrin solution against Aspergillus fumigatus was assessed in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis and compared with that of amphotericin B. Oral itraconazole solution at dosages of 20 and 40 mg/kg/day improved survival as compared with that of controls. Itraconazole (40 mg/kg/day) not only improved survival and reduced antigen levels but also significantly eradicated A. fumigatus from tissues and was as effective as amphotericin B in these studies. The higher dose of itraconazole produced higher levels in serum, which correlated with improved efficacy of the drug. This itraconazole-cyclodextrin solution was well absorbed and was effective in the treatment of experimental invasive aspergillosis; it demonstrates the potential of this class of agents in improving therapy for invasive aspergillosis.

Amphotericin B↗

Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole.

Amphotericin B and fluconazole susceptibilities of 13 Cryptococcus neoformans isolates from five patients with recurrent cryptococcal meningitis were determined. For each patient, serial isolates showed no increase in antibiotic resistance relative to the initial isolate. For these patients, recurrent disease was not due to drug resistance but may reflect changes in immune function and/or poor compliance.

AIDS-Related Opportunistic Infections↗

Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients.

Because the use of fluconazole prophylaxis had been associated with an increased rate of Candida krusei infections at The John Hopkins Oncology Center, early empiric amphotericin B plus flucytosine were given to febrile neutropenic patients colonized by C. krusei. By this practice, the proportion of fungemias attributable to C. krusei was low (12.5%) in patients receiving fluconazole over a 6-month interval. However, Torulopsis (Candida) glabrata assumed a much higher proportion of fungemias (75%) among patients receiving fluconazole. In vitro susceptibility testing combined with this clinical experience suggests that some T. glabrata isolates are not susceptible to fluconazole and can cause breakthrough infections in patients receiving fluconazole.

Amphotericin B↗

Antifungal susceptibility testing.

Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work.

Animals↗

Disseminated hyalohyphomycosis caused by a novel human pathogen, Fusarium napiforme.

Fusarium species are saprophytic molds and important plant pathogens, although they are increasingly recognized as agents of human mycosis. Frequently, the infection is superficial. Deep tissue infection may occur as an opportunistic hyalohyphomycosis, and wide dissemination is common in immunocompromised hosts. We describe a novel case of disseminated hyalohyphomycosis caused by F. napiforme in a patient with acute myelogenous leukemia. The clinical manifestations of this infection were similar to those attributed to infection with other species. In vitro susceptibility testing demonstrated resistance to amphotericin B and flucytosine, and progressive infection was documented until recovery of granulocyte function. The distinguishing clinical mycologic characteristics of this opportunistic mold are the unique turnip- or lemon-shaped microconidia. F. napiforme is a new agent of hyalohyphomycosis, further emphasizing the importance of Fusarium species as opportunistic molds.

Adult↗

Antifungal susceptibility testing. Current state of technology, limitations, and standardization.

In parallel with the escalating incidence of serious, invasive fungal infections in the immune-compromised host has been the development and use of new, potentially efficacious antifungal agents as well as recognition of both primary and secondary resistance to such drugs by the etiologic mycotic agents. These findings have generated considerable enthusiasm for a reproducible and standardized means for the laboratory evaluation of antifungal drugs. For over a decade, global investigations have ensued in the hope of generating laboratory methods analogous to those used for antibacterial drugs that may predict the optimal therapeutic choice for clinicians treating mycoses. This article reviews the background, history, and development of in vitro antifungal susceptibility efforts, details the problems inherent in this area of laboratory medicine/infectious diseases, and assesses the contemporary aspects of standardization.

Antifungal Agents↗

Nomenclature of fungal diseases: a report and recommendations from a Sub-Committee of the International Society for Human and Animal Mycology (ISHAM).

The ISHAM Mycoses Nomenclature Committee has considered the present status of fungal disease names. It suggests that the traditional approach to mycoses nomenclature in which the name of a causative taxon is suffixed with '-asis', '-iasis', '-osis' or '-mycosis' leads to names that are frequently unstable with respect to subsequent taxonomic and clinico-epidemiological changes. It is therefore recommended that individual mycoses should be named as often as possible in the form 'pathology A due to/caused by fungus X' or '[adjectival] fungus X pathology A' in preference to construction of names based solely on fungal taxa. A list of recommended mycosis names retained for their long tradition or intrinsic convenience is provided, together with a combined index and list of rejected names.

Animals↗