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Biomedical subjects

M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 73 records · Page 4Linked to original sources

Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer.

Oral mucosal colonization and infection with Candida are common in patients receiving radiation therapy for head and neck cancer. Infection is marked by oral pain and/or burning and can lead to significant patient morbidity. The purpose of this study was to identify Candida strain diversity in this population by using a chromogenic medium, subculturing, molecular typing, and antifungal susceptibility testing of clinical isolates. These results were then correlated with clinical outcome in patients treated with fluconazole for infection. Specimens from 30 patients receiving radiation therapy for head and neck cancer were cultured weekly for Candida. Patients exhibiting clinical infection were treated with oral fluconazole. All isolates were plated on CHROMagar Candida and RPMI medium, subcultured, and submitted for antifungal susceptibility testing and molecular typing. Infections occurred in 27% of the patients and were predominantly due to Candida albicans (78%). Candida carriage occurred in 73% of patients and at 51% of patient visits. Yeasts other than C. albicans predominated in carriage, as they were isolated from 59% of patients and at 52% of patient visits. All infections responded clinically, and all isolates were susceptible to fluconazole. Molecular typing showed that most patients had similar strains throughout their radiation treatment. One patient, however, did show the acquisition of a new strain. With this high rate of infection (27%), prophylaxis to prevent infection should be evaluated for these patients.

Antifungal Agents↗

Human phaeohyphomycotic osteomyelitis caused by the coelomycete Phomopsis saccardo 1905: criteria for identification, case history, and therapy.

The Sphaeropsidales, coelomycetous fungi producing asexual conidia within enclosed conidiomata (pycnidia), are saprobic on numerous vascular plants. Despite their ubiquitous nature, only a limited number of genera have been documented as causing human disease. We report what we believe to be the first human case of osteomyelitis due to a Phomopsis species in a chronically immunosuppressed female. The patient developed a subcutaneous abscess on the distal phalanx of the right fourth finger complicated by osteomyelitis. Operative specimens revealed fungal hyphae and a pure culture of mould. The patient was treated with a 6-month course of itraconazole. At 16 months of follow-up, she remained free of recurrence. Phomopsis species differ from the similar, more frequently reported Phoma species by having immersed, thick-walled, multiloculate conidiomata and by the production of alpha (short, ellipsoidal) and beta (long, filamentous) conidia.

Arthritis, Rheumatoid↗

Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: species identification and review of the literature.

Trichoderma longibrachiatum was recovered from stool surveillance cultures and a perirectal ulcer biopsy specimen from a 29-year-old male who had received an allogeneic bone marrow transplant for acute lymphoblastic leukemia. The amphotericin B (2.0 microgram/ml) and itraconazole (1.0 microgram/ml) MICs for the organism were elevated. Therapy with these agents was unsuccessful, and the patient died on day 58 posttransplantation. At autopsy, histologic sections from the lungs, liver, brain, and intestinal wall showed infiltration by branching septate hyphae. Cultures were positive for Trichoderma longibrachiatum. While Trichoderma species have been recognized to be pathogenic in profoundly immunosuppressed hosts with increasing frequency, this is the first report of probable acquisition through the gastrointestinal tract. Salient features regarding the identification of molds in the Trichoderma longibrachiatum species aggregate are presented.

Adult↗

Pseudoepidemic of Aspergillus niger infections traced to specimen contamination in the microbiology laboratory.

We report a pseudo-outbreak of Aspergillus niger that followed building construction in our clinical microbiology laboratory. Because outbreaks of invasive aspergillosis have been linked to hospital construction, strategies to minimize dust in patient care areas are common practice. We illustrate that the impact of false-positive cultures on patient care should compel laboratories to prevent specimen contamination during construction.

Aspergillosis↗

In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole.

Amphotericin B therapy continues to be the "gold standard" in the treatment of invasive aspergillosis in the immunocompromised host. Although Aspergillus fumigatus and Aspergillus flavus constitute the major species, several reports have described invasive pulmonary or disseminated disease due to the less common Aspergillus terreus and dismal clinical outcomes with high-dose amphotericin B. We therefore evaluated 101 clinical isolates of A. terreus for their susceptibility to amphotericin B and the investigational triazole voriconazole by using the National Committee for Clinical Laboratory Standards M27-A method modified for mould testing. Forty-eight-hour MICs indicated 98 and 0% resistance to amphotericin B and voriconazole, respectively. We conclude that A. terreus should be added to the list of etiologic agents refractory to conventional amphotericin B therapy and suggest the potential clinical utility of voriconazole in aspergillosis due to this species.

Amphotericin B↗

Elucidating the origins of nosocomial infections with Candida albicans by DNA fingerprinting with the complex probe Ca3.

Computer-assisted DNA fingerprinting with the complex probe Ca3 has been used to analyze the relatedness of isolates collected from individuals with nosocomial bloodstream infections (BSIs) and hospital care workers (HCWs) in the surgical and neonatal intensive care units (ICUs) of four hospitals. The results demonstrate that for the majority of patients (90%), isolates collected from commensal sites before and after collection of a BSI isolate were highly similar or identical to the BSI isolate. In addition, the average similarity coefficient for BSI isolates was similar to that for unrelated control isolates. However, the cluster characteristics of BSI isolates in dendrograms generated for each hospital compared to those of unrelated control isolates in a dendrogram demonstrated a higher degree of clustering of the former. In addition, a higher degree of clustering was observed in mixed dendrograms for HCV isolates and BSI isolates for each of the four test hospitals. In most cases, HCW isolates from an ICU were collected after the related BSI isolate, but in a few cases, the reverse was true. Although the results demonstrate that single, dominant endemic strains are not responsible for nosocomial BSIs in neonatal ICUs and surgical ICUs, they suggest that multiple endemic strains may be responsible for a significant number of cases. The results also suggest that cross-contamination occurs between patients and HCWs and between HCWs in the same ICU and in different ICUs. The temporal sequence of isolation also suggests that in the majority of cases HCWs are contaminated by isolates from colonized patients, but in a significant minority, the reverse is true. The results of this study provide the framework for a strategy for more definitive testing of the origins of Candida albicans strains responsible for nosocomial infections.

Candida albicans↗

A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: clinical outcomes and development of fluconazole resistance.

PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known. PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates. RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day. CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent.

AIDS-Related Opportunistic Infections↗

National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species.

The National Epidemiology of Mycoses Survey (NEMIS) involves six academic centers studying fungal infections in surgical and neonatal intensive care unit (ICU) patients. We studied variation in species and strain distribution and anti-fungal susceptibility of 408 isolates of Candida spp. Candida spp. were isolated from blood, other normally sterile site cultures, abscesses, wounds, catheters, and tissue biopsies of 141 patients hospitalized in the surgical (107 patients) and neonatal (34 patients) ICUs of medical centers located in Oregon, Iowa, California, Texas, Georgia, and New York. Isolates were also obtained from selected colonized patients (16 patients) and the hands of health care workers (27 individuals). DNA typing was performed using pulsed field gel electrophoresis, and antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards (NCCLS) methods. Important variation in susceptibility to itraconazole and fluconazole was noted: MICs of itraconazole ranged from 0.25 microgram/mL (MIC90) in Texas to 2.0 micrograms/mL (MIC90) in New York. Similarly, the MIC90 for fluconazole was higher for isolates from New York (64 micrograms/mL) compared to the other sites (8-16 micrograms/mL). In general, DNA typing revealed patient-unique strains; however, there were 13 instances of possible cross-infection noted in 5 of the medical centers. Notably, 9 of the 13 clusters involved species of Candida other than C. albicans. Potential transmission from patient-to-patient (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis) and health care worker-to-patient (C. albicans, C. parapsilosis, C. krusei) was noted in both surgical ICU and neonatal ICU settings. These data provide further insight into the epidemiology of nosocomial candidiasis in the ICU setting.

Amphotericin B↗

Clinical evaluation and microbiology of oropharyngeal infection due to fluconazole-resistant Candida in human immunodeficiency virus-infected patients.

Signs and symptoms of oropharyngeal candidiasis (OPC) were correlated with microbiology and clinical response to fluconazole in a cohort of patients with advanced human immunodeficiency virus (HIV) infection and recurrent OPC. Sixty-four HIV-infected patients with a median CD4 cell count of < 50/mm3 (range, 3-318/mm3) who presented with OPC were enrolled in a longitudinal study. Specimens for cultures were taken weekly until clinical resolution. Therapy with fluconazole was increased weekly as required to a maximum daily dose of 800 mg until resolution of symptoms and oral lesions. Resistant or dose-dependent susceptible yeasts, defined as a minimum inhibitory concentration of > or = 16 micrograms/mL, were detected in 48 (31%) of 155 episodes. Clinical resolution with fluconazole therapy occurred in 107 (100%) of 107 episodes with susceptible yeasts vs. 44 (92%) of 48 episodes with resistant or dose-dependent susceptible strains (P = .008). Patients from whom fluconazole-resistant yeasts were isolated required longer courses of therapy and higher doses of fluconazole for response, but overall, excellent responses to fluconazole were seen in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗

Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia.

Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.

Amphotericin B↗

Successful medical therapy for deeply invasive facial infection due to Pythium insidiosum in a child.

Pythiosis occurs in animals and humans who encounter aquatic habitats that harbor Pythium insidiosum. Drug therapy for deeply invasive infections with this organism has been ineffective in humans and animals; patients have been cured only by radical surgical debridement. A 2-year-old boy developed periorbital cellulitis unresponsive to antibiotic and antifungal therapy. The cellulitis extended to the nasopharynx, compromising the airway and necessitating a gastrostomy for feeding. P. insidiosum was isolated from surgical biopsy specimens of the affected tissue. On the basis of in vitro susceptibility studies of the isolate, the patient was treated with a combination of terbinafine and itraconazole. The infection resolved over a period of a few months. The patient remained well 1.5 years after completing a 1-year course of therapy. Cure of deep P. insidiosum infection is feasible with drug therapy.

Anti-Infective Agents↗

Acute invasive sinusitis due to Trichoderma longibrachiatum in a liver and small bowel transplant recipient.

We describe a case of acute invasive sinusitis due to an unusual moniliaceous fungus, Trichoderma longibrachiatum Rifai 1969 (a member of the class Hyphomycetes), in a small bowel and liver transplant recipient treated with tacrolimus (FK-506) and prednisone. The patient was successfully treated with surgical debridements and amphotericin B followed by oral itraconazole.

Acute Disease↗

Treatment of histoplasmosis with MK-991 (L-743,872).

BALB/c nu/+ immunocompetent and athymic (nu/nu) mice were infected intravenously with yeast cells of Histoplasma capsulatum. Mice were either given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survival or reduction in tissue counts. MK-991 was protective in immunocompetent mice, prolonging survival and reducing counts in spleen and livers at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modestly effective in athymic mice at a higher dose, 5 mg/kg/day. These studies suggest that MK-991 may be appropriate for clinical development in histoplasmosis.

Animals↗

Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models.

Nine isolates of filamentous fungi previously tested in 11 different laboratories for their susceptibilities to amphotericin B and itraconazole in vitro were injected intravenously into mice and guinea pigs, and responses to treatment with both agents were studied. The experiments were done in a single laboratory. Mean survival times, the percentages of animals surviving 12 days after infection, and culture results for samples of deep organs obtained postmortem were used as markers of antifungal efficacy. Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusarium spp. in mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments. Among the infections that could be evaluated, some degree of response to the corresponding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at < 0.5 microg/ml and Aspergillus spp. isolates susceptible to itraconazole at < 1.0 microg/ml. Conversely, no responses were apparent with infecting strains for which MICs were > or = 2 microg/ml (amphotericin B) or > or = 1 microg/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn.

Amphotericin B↗

Susceptibilities of clinical and laboratory isolates of Blastomyces dermatitidis to ketoconazole, itraconazole, and fluconazole.

Eighteen isolates of Blastomyces dermatitidis were evaluated for their in vitro susceptibilities to ketoconazole, itraconazole, and fluconazole. The MIC ranges were 0.1 to 0.4 microg/ml for ketoconazole, < or =0.018 to 0.07 microg/ml for itraconazole, and 2.5 to 4.0 microg/ml for fluconazole. The ranges for the minimal lethal concentrations were 0.2 to 0.8 microg/ml for ketoconazole, < or =0.018 to 0.07 microg/ml for itraconazole, and 10 to 40 microg/ml for fluconazole. Itraconazole was the most active agent against B. dermatitidis in vitro, while fluconazole was the least active. These results correlate with the clinical efficacies noted to date with doses of these agents used to treat blastomycosis.

Antifungal Agents↗

Interpretation of trailing endpoints in antifungal susceptibility testing by the National Committee for Clinical Laboratory Standards method.

Trailing endpoints remain a problem in antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards (NCCLS) method. For isolates for which trailing endpoints are found, MICs of < or = 1 microg/ml at 24 h and of > 64 microg/ml at 48 h are usually observed. In a study of human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis, we identified three patients with multiple serial isolates for which trailing endpoints were observed with fluconazole. At 24 h, MICs were generally < or = 1 microg/ml by both broth macro- and microdilution methods. However, at 48 h, MICs were > 64 microg/ml, while the organism remained susceptible by agar dilution testing with fluconazole. Most episodes of oropharyngeal candidiasis with trailing-endpoint isolates responded to doses of fluconazole as low as 100 mg/day. Two patients had both susceptible and trailing-endpoint isolates by NCCLS broth macro- and microdilution testing; these isolates were found to be the same strain by pulsed-field gel electrophoresis using restriction fragment length polymorphisms. Another patient had two different strains, one for which trailing endpoints were observed and one which was susceptible at 48 h. Trailing endpoints may be seen with selected isolates of a strain or may be a characteristic finding for most or all isolates of a strain. In addition, with isolates for which trailing endpoints are observed, reading the endpoint for the NCCLS method at 24 h may be more appropriate.

Antifungal Agents↗

Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar candida screening and susceptibility testing of isolates.

Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from </=0.125 to 64 microgram/ml. Two isolates were resistant to fluconazole (MIC, 64 microgram/ml) and one strain was dose dependent susceptible (MIC, 16 microgram/ml). MICs of other azoles, including voriconazole, itraconazole, and SCH 56592, for these isolates were lower. C. dubliniensis was identified in 11 of 63 (17%) serially evaluated patients. Variability in phenotypic characteristics dictates the use of molecular and biochemical techniques to identify C. dubliniensis. This study identifies C. dubliniensis in HIV-infected patients from San Antonio, Tex., and shows that C. dubliniensis is frequently detected in those patients by using a primary CHROMagar screen.

AIDS-Related Opportunistic Infections↗