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M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 19 recordsLinked to original sources

Multicenter comparison of the VITEK 2 yeast susceptibility test with the CLSI broth microdilution reference method for testing fluconazole against Candida spp.

A fully automated commercial antifungal susceptibility test system (VITEK 2 yeast susceptibility test; bioMerieux, Inc., Hazelwood, Mo.) was compared in three different laboratories with Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) method by testing two quality control strains and a total of 426 isolates of Candida spp. (103 to 135 clinical isolates in each laboratory plus 80 challenge isolates in one laboratory) against fluconazole. Reference BMD MIC endpoints were established after 24 and 48 h of incubation. VITEK 2 endpoints were determined spectrophotometrically after 10 to 26 h of incubation (mean, 13 h). Excellent essential agreement (within two dilutions) between the VITEK 2 and the 24- and 48-h BMD MICs was observed. The overall agreement values were 97.9 and 93.7%, respectively. Both intra- and interlaboratory agreement was 100%. The overall categorical agreement between VITEK 2 and BMD was 97.2% at the 24-h BMD time point and 88.3% at the 48-h BMD time point. Decreased categorical agreement at 48 h was attributed to trailing growth observed with Candida glabrata. The VITEK 2 system reliably detected fluconazole resistance among Candida spp. and demonstrated excellent quantitative and qualitative agreement with the reference BMD method.

Antifungal Agents↗

In vitro-clinical correlations for amphotericin B susceptibility in AIDS-associated cryptococcal meningitis.

Reliable measures of antifungal drug susceptibility are needed. We tested the susceptibility of Cryptococcus neoformans from patients treated with amphotericin B. In vitro susceptibility employed a modified broth macrodilution method. We demonstrate a strong correlation between the quantitative measures of in vitro amphotericin B susceptibility and the quantitative response observed in patients.

AIDS-Related Opportunistic Infections↗

Interlaboratory study of quality control isolates for a broth microdilution method (modified CLSI M38-A) for testing susceptibilities of dermatophytes to antifungals.

The Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards, or NCCLS) M38-A standard for the susceptibility testing of filamentous fungi does not specifically address the testing of dermatophytes. In 2003, a multicenter study investigated the reproducibility of the microdilution method developed at the Center for Medical Mycology, Cleveland, Ohio, for testing the susceptibility of dermatophytes. Data from that study supported the introduction of this method for testing dermatophytes in the future version of the CLSI M38-A standard. In order for the method to be accepted by CLSI, appropriate quality control isolates needed to be identified. To that end, an interlaboratory study, involving the original six laboratories plus two additional sites, was conducted to evaluate potential candidates for quality control isolates. These candidate strains included five Trichophyton rubrum strains known to have elevated MICs to terbinafine and five Trichophyton mentagrophytes strains. Antifungal agents tested included ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole. Based on the data generated, two quality control isolates, one T. rubrum isolate and one T. mentagrophytes isolate, were identified and submitted to the American Type Culture Collection (ATCC) for inclusion as reference strains. Ranges encompassing 95.2 to 97.9% of all data points for all seven drugs were established.

Antifungal Agents↗

Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature.

Zygomycetes are ubiquitous fungi that can cause invasive disease associated with high mortality. We report 10 solid organ transplant recipients with zygomycosis (incidence 2 per 1000) and reviewed 106 cases in the English-language literature. These included renal (n = 73), heart (n = 16), lung (n = 4), heart/lung (n = 2), liver (n = 19) and kidney/pancreas (n = 2) transplant recipients. All patients were receiving immunosuppression and the vast majority steroids. The clinical presentation included rhino-sino-orbital (n = 20), rhinocerebral (n = 16), pulmonary (n = 28), gastrointestinal (n = 13), cutaneous (n = 18), renal (n = 6) and disseminated disease (n = 15). Most frequently isolated genera were Rhizopus (73%) followed by Mucor (13%). The overall mortality was 49%. While rhino-sino-orbital disease had the best prognosis, rhinocerebral disease had high mortality (93%) comparable to disseminated disease. A favorable outcome was associated with limited, surgically accessible disease and early surgical intervention along with amphotericin B administration.

Hospitals, University↗

Isolated endogenous endophthalmitis due to a sporodochial-forming Phialemonium curvatum acquired through intracavernous autoinjections.

We report a case of endogenous endophthalmitis due to a sporodochial-forming species of Phialemonium curvatum. The infection led to the enucleation of the affected eye, but there was no evidence of systemic dissemination. The isolated P. curvatum produced aggregates of phialides, many occurring on coils or in verticils, which eventually develop into sporodochia. The initial and post-enucleation isolates revealed they were identical to strains of P. curvatum from Israel causing disseminated disease in patients practicing intracavernous autoinjections for the treatment of erectile dysfunction. The reported case had unusual clinical and microbiological features. Despite the route of acquisition and the lack of systemic antifungal therapy, the infection did not spread beyond the eye. The morphology of the phialides aggregates was also unique, and the distinction between Volutella and Acremonium is discussed. This case expands the spectrum of infections due to Phialemonium species, and reveals a novel way of developing fungal endophthalmitis.

Aged↗

Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints.

Developing interpretive breakpoints for any given organism-drug combination requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic parameters, and the relationship between the in vitro activity and outcome from both in vivo and clinical studies. Using data generated by standardized broth microdilution and disk diffusion test methods, the Antifungal Susceptibility Subcommittee of the Clinical and Laboratory Standards Institute has now proposed interpretive breakpoints for voriconazole and Candida species. The MIC distribution for voriconazole was determined using a collection of 8,702 clinical isolates. The overall MIC90 was 0.25 microg/ml and 99% of the isolates were inhibited at < or = 1 microg/ml of voriconazole. Similar results were obtained for 1,681 Candida isolates (16 species) from the phase III clinical trials. Analysis of the available data for 249 patients from six phase III voriconazole clinical trials demonstrated a statistically significant correlation (P = 0.021) between MIC and investigator end-of-treatment assessment of outcome. Consistent with parallel pharmacodynamic analyses, these data support the following MIC breakpoints for voriconazole and Candida species: susceptible (S), < or = 1 microg/ml; susceptible dose dependent (SDD), 2 microg/ml; and resistant (R), > or = 4 microg/ml. The corresponding disk test breakpoints are as follows: S, > or = 17 mm; SDD, 14 to 16 mm; and R, < or = 13 mm.

Antifungal Agents↗

Successful therapy of cerebral phaeohyphomycosis due to Ramichloridium mackenziei with the new triazole posaconazole.

Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei is universally fatal. All reported cases with long-term follow-up have indicated 100% mortality despite antifungal therapy and surgical intervention. We describe the case of a 62-year-old patient who underwent renal transplantation and had a cerebral abscess caused by R. mackenziei. The infection progressed despite surgical evacuation and therapy with liposomal amphotericin B, itraconazole, and 5-flucytosine. The patient was subsequently treated with the investigational triazole posaconazole oral suspension, 800 mg/day, in divided doses. Treatment with posaconazole resulted in progressive clinical and radiologic improvement. The patient is alive four years after diagnosis and maintained on posaconazole therapy. This case supports the potential role of this extended-spectrum azole in the treatment of this serious fungal infection of the central nervous system.

Antifungal Agents↗

Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium.

This report describes MRI findings of a rare case of biopsy-proven fatal cerebral infection with Chaetomium strumarium in a 28-year-old man with a history of i.v. drug abuse. Magnetic resonance imaging revealed rapidly progressing lesions with irregular peripheral enhancement, possible central haemorrhage and significant mass effect. Only six cases of cerebral infection with Chaetomium have been reported in the English literature. This is the first report in the radiology literature describing the imaging findings. The previously reported cases of cerebral infection by the Chaetomium species are also reviewed.

Adult↗

Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 140,767 yeasts were collected from 127 participating investigators in 39 countries from June 1997 through December 2003. Data were collected on 79,343 yeast isolates tested with voriconazole from 2001 through 2003. All investigators tested clinical yeast isolates by the CLSI (formerly NCCLS) M44-A disk diffusion method. Test plates were automatically read and results were recorded with the BIOMIC Vision Image Analysis System. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly via e-mail for analysis. Duplicate (the same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. The 10 most common species of yeasts all showed less resistance to voriconazole than to fluconazole. Candida krusei showed the largest difference, with over 70% resistance to fluconazole and less than 8% to voriconazole. All species of yeasts tested were more susceptible to voriconazole than to fluconazole, assuming proposed interpretive breakpoints of > or =17 mm (susceptible) and < or =13 mm (resistant) for voriconazole. MICs reported in this study were determined from the zone diameter in millimeters from the continuous agar gradient around each disk, which was calibrated with MICs determined from the standard CLSI M27-A2 broth dilution method by balanced-weight regression analysis. The results from this investigation demonstrate the broad spectrum of the azoles for most of the opportunistic yeast pathogens but also highlight several areas where resistance may be progressing and/or where previously rare species may be "emerging."

Antifungal Agents↗

Identification and first report of Inonotus (Phellinus) tropicalis as an etiologic agent in a patient with chronic granulomatous disease.

Although isolates of filamentous basidiomycetes can usually be recognized in a clinical laboratory setting, identification is problematic, as they seldom exhibit diagnostic morphological features formed in nature. This paper is the first report of Inonotus (Phellinus) tropicalis inciting human disease and describes the methods used to support the identification.

Adult↗

Cloning and characterization of the lanosterol 14alpha-demethylase (ERG11) gene in Cryptococcus neoformans.

The ergosterol pathway in fungal pathogens is an attractive antimicrobial target because it is unique from the major sterol (cholesterol) producing pathway in humans. Lanosterol 14alpha-demethylase is the target for a major class of antifungals, the azoles. In this study we have isolated the gene for this enzyme from Cryptococcus neoformans. The gene, ERG11, was recovered using degenerate PCR with primers designed with a novel algorithm called CODEHOP. Sequence analysis of Erg11p identified a highly conserved region typical of the cytochrome P450 class of mono-oxygenases. The gene was present in single copy in the genome and mapped to one end of the largest chromosome. Comparison of the protein sequence to a number of major human fungal pathogen Erg11p homologs revealed that the C. neoformans protein was highly conserved, and most closely related to the Erg11p homologs from other basidiomycetes. Functional studies demonstrated that the gene could complement a Saccharomyces cerevisiae erg11 mutant, which confirmed the identity of the C. neoformans gene.

Algorithms↗

Comparison of antifungal susceptibilities to fluconazole and voriconazole of oral Candida glabrata isolates from head and neck radiation patients.

The antifungal susceptibilities of 79 oral Candida glabrata isolates to fluconazole and voriconazole were compared. The MICs at which 90% of the isolates tested were inhibited were 1 microg of voriconazole/ml and 32 microg of fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are elevated are commonly those for which the voriconazole MICs are elevated, but these increases may be transient for voriconazole, as they are for fluconazole.

Antifungal Agents↗

Intra- and interlaboratory study of a method for testing the antifungal susceptibilities of dermatophytes.

The National Committee for Clinical Laboratory Standards (NCCLS) M38-A standard for the susceptibility testing of conidium-forming filamentous fungi does not explicitly address the testing of dermatophytes. This multicenter study, involving six laboratories, investigated the MIC reproducibility of seven antifungal agents tested against 25 dermatophyte isolates (5 blinded pairs of five dermatophyte species per site for a total of 300 tests), using the method of dermatophyte testing developed at the Center for Medical Mycology, Cleveland, Ohio. The dermatophytes tested included Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis. Seven antifungals with activity against dermatophytes were tested, including ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole. Interlaboratory MICs for all isolates were in 92 to 100% agreement at a visual endpoint reading of 50% inhibition as compared to the growth control and 88 to 99% agreement at a visual endpoint reading of 80% inhibition as compared to the growth control. Intralaboratory MICs between blinded pairs were in 97% agreement at a visual endpoint reading of 50% inhibition as compared to the growth control and 96% agreement at a visual endpoint reading of 80% inhibition as compared to the growth control. Data from this study support consideration of this method as an amendment to the NCCLS M38-A standard for the testing of dermatophytes.

Antifungal Agents↗

Exophiala oligosperma causing olecranon bursitis.

A 62-year-old male with a history of Wegener's granulomatosis and immunosuppressive therapy presented with chronic olecranon bursitis. A black velvety mould with brown septate hyphae and tapered annellides was isolated from a left elbow bursa aspirate and was identified as an Exophiala species. Internal transcribed sequence rRNA sequencing showed the isolate to be identical to Exophiala oligosperma. The patient was successfully treated with aspiration and intrabursal amphotericin B.

Bursa, Synovial↗

Cyclical behavior of bone remodeling and bone loss in healthy women after menopause: results of a prospective study.

Annual changes in lumbar bone mineral density (LBMD) and bone remodeling markers were measured in 238 healthy pre- and postmenopausal women, aged 45-74 years. The subjects were divided into groups according to their menstrual status and years since menopause. The results obtained indicate that bone loss is not a constant process over time but rather exhibits cyclical damping oscillations. When the log-linear trend of LBMD decrement was transformed into a constant by considering annual percentage changes, the presence of a cyclical component of 7 years was evident. By employing a harmonic regression model, the cyclical component was also statistically significant on baseline data. The cyclical behavior of LBMD decrement corresponded to an analogous behavior of the bone remodeling markers. These results suggest that a lack of estrogen acts as a synchronizer on bone remodeling by triggering a latent cyclical rhythm of bone loss that persists throughout life after menopause. The existence of a chronobiological rhythm of bone loss starting after menopause, if confirmed, could have important clinical implications.

Aged↗

In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592).

We investigated the in vitro susceptibilities of 213 cerebrospinal fluid isolates of Cryptococcus neoformans isolated from 192 patients through a 10-year period, 1990-99, against fluconazole, voriconazole and posaconazole (SCH56592) by using the NCCLS (National Committee for Clinical Laboratory Standards) macrodilution method, M27-A. The overall MICs50 and MICs90 of fluconazole, voriconazole and posaconazole were found to be 2 and 8 micro g ml-1, <or=0.125 micro g ml-1 (both), and <or=0.015 and 0.06 micro g ml-1, respectively. The MIC ranges, MICs50, and MICs90 of three triazoles were also determined according to the defined year category (1990-94, 1995, 1996, 1997 and 1998-99). The MICs50 and MICs90 of each triazole remained almost unchanged and did not exhibit any sign of an upward shift during a decade (1990-99). However, a tendency for development of possible cross-resistance between the three triazoles was observed only in 1996. Meanwhile, the individual relapsing isolates (n:21) from 20 patients exhibited same, higher or, suprisingly, lower MICs, particularly against fluconazole and posaconazole.

Antifungal Agents↗