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Biomedical subjects

M G Rinaldi

Publications and source records attributed to M G Rinaldi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Trichoderma longibrachiatum infection in a pediatric patient with aplastic anemia.

Trichoderma longibrachiatum infection of the skin in an 11-year-old child with severe aplastic anemia and prolonged neutropenia is reported. The patient received systemic antifungal therapy and underwent bone marrow transplantation. To our knowledge, this is the first description of T. longibrachiatum infection in a pediatric patient. It also is the first case successfully treated with medical therapy. A review of the literature suggests that Trichoderma spp. are recognized as human pathogens with increasing frequency, particularly for immunocompromised patients, and should be considered in the differential diagnosis of fungal infections in the pediatric population.

Amphotericin B↗
PubMed1997

An aberrant variant of Histoplasma capsulatum var. capsulatum.

We studied an aberrant culture of Histoplasma capsulatum var. capsulatum isolated from synovial fluid collected from the right elbow of a patient from Kansas. Colonies on Sabouraud glucose agar and other routine mycological media were glabrous to soft, moist, heaped, deeply folded or convoluted, and orange-brown with a white, irregular margin. Microscopically, hyphae were hyaline, septate, and branched and remained totally devoid of conidiation over a period of 2 years on all mycological media. Conversion to the yeast form was achieved on Pine's medium at 37 degrees C. Colonies at early stages of growth were smooth, moist, pasty, shiny, and orange-brown but soon became wrinkled and slightly raised and produced oval, thin-walled cells measuring 2 to 3 by to 4.5 microns which multiplied by polar budding. The identity of the isolate was further confirmed by utilizing the Accuprobe DNA and the exoantigen test for H. capsulatum var. capsulatum.

DNA Probes↗
PubMed1997

Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection.

Five Candida albicans colonies from each infection in AIDS patients receiving fluconazole therapy for oropharyngeal candidiasis over a 2-year period were evaluated by antifungal susceptibility testing and DNA subtyping, and the results were correlated with clinical response to determine the occurrence of clinically significant selection of more-resistant C. albicans over multiple infections. A total of 534 C. albicans isolates were obtained from 38 patients who exhibited 84 episodes of infection. Antifungal susceptibility testing revealed that the MICs for 93% of the isolates were < or = 8.0 microg/ml and the MICs for 7% of the isolates were > or = 64 microg/ml. DNA subtyping revealed 70 different subtypes, with 78% of patients with one infection exhibiting one DNA subtype and 80% of patients with more than one infection exhibiting multiple DNA subtypes. Also, patients who had multiple infections had lower CD4 counts than those with single infections. Differences between the single-infection group and the multiple-infection group regarding the number of DNA subtypes and CD4 counts were both statistically significant. Of the 74 evaluable infections all were successfully treated with regular-dose (100-mg/day) fluconazole, except for three patients who ultimately responded to higher-dose fluconazole. Only one patient may have shown clinically significant selection of a more-resistant C. albicans strain over multiple courses of treatment. Interestingly, MICs reached only 8.0 microg/ml, even though doses of 400 mg of fluconazole were necessary for clinical cure.

AIDS-Related Opportunistic Infections↗
PubMed1997

Controversies in medical mycology.

Questions and controversies involving many aspects of medical mycology have increased in recent years. Case histories are described in which fungal infection causes unexpected and atypical problems. Molecular techniques of diagnosis need to be used alongside traditional culture methods. Increased drug use has led to genuine concerns and differing views regarding the definition and development of resistance by fungi. The use and value of combinational antifungal therapy and the employment of immunomodulatory agents concomitant with antimycotics have been debated. Nonetheless, good standards have been developed in the testing of antifungal agents. These, together with the commercial viability of antifungal drugs and hence increased interest in their development, mean that although we have entered the golden age of mycology we have also entered the golden age of antifungal therapy.

Adolescent↗
PubMed1997

Amphotericin B enzyme-linked immunoassay for clinical use: comparison with bioassay and HPLC.

OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) for amphotericin B in serum samples. Results are compared with those obtained by HPLC and bioassay. DESIGN: Comparison of results obtained by ELISA, HPLC, and bioassay. METHODS: We developed a new ELISA using a polyclonal rabbit antibody to measure serum amphotericin B concentrations. Blinded samples of amphotericin B in concentrations of 0.15-78 micrograms/mL were prepared in human serum and assayed simultaneously by the ELISA, HPLC, and bioassay. The results of each assay were derived from standard curves and evaluated by using the Table Curve 2D computer program. These data were compared by using correlation analysis with evaluation of Pearson's correlation coefficient by Student's t-test. RESULTS: ELISA and bioassay compared favorably at amphotericin B concentrations of 0.3-20 micrograms/mL with a correlation coefficient of r = 0.993, while ELISA and HPLC compared with a correlation coefficient of r = 0.944. The average coefficient of variation over the range 0.3-20.0 micrograms/mL was 28% +/- 7% for HPLC, 26% +/- 9% for ELISA, and 13% +/- 4% for bioassay. Comparison of all three assays revealed the highest correlation with the ELISA assay (r = 0.998) for the range of concentrations (0.3-20 micrograms/mL) routinely achieved. Samples containing concentrations in excess of 20 micrograms/mL could be diluted. Desiccation for concentrations less than 0.3 microgram/mL was not tested. CONCLUSION: The determination of serum amphotericin B concentrations by ELISA gave results similar to those obtained by a bioassay and HPLC technique. Although variability appears greater with ELISA, the ease of performing yjis assay expedites the evaluation of amphotericin B concentrations from lipid formulations without interference from coadministered antibacterials of azole antifungals.

Amphotericin B↗
PubMed1997

Ocular penetration and pharmacokinetics of topical fluconazole.

The high bioavailability and low toxicity of fluconazole, a stable, water-soluble, low-molecular-weight bis-triazole antifungal, makes it a good candidate for consideration as a topical ocular agent. The penetration of fluconazole (0.2%) into the corneas and aqueous humors of New Zealand white rabbits was assayed by gas liquid chromatography (GLC). Peak corneal levels occurred essentially immediately at 5 min in the corneas [debrided, 8.2 +/- 1.2 micrograms/g; nondebrided, 1.6 +/- 0.6 microgram/g; (mean +/- SEM)] and at 15 min after application in the aqueous [debrided, 9.4 +/- 2.3 micrograms/ml; nondebrided, 1.6 +/- 0.6 microgram/ml; (mean +/- SEM)]. Estimating from semilogarithmic plots of the data, the halflife (t1/2) in the debrided eyes was 15 min; in the nondebrided eyes, t1/2 was 30 min. A loading dose of a 20-microliter drop per min for 5 min yielded levels of 59.9 +/- 11.3 micrograms/g (mean +/- SEM) in the debrided corneas and 32.4 +/- 1.9 micrograms/ ml (mean +/- SEM) in the corresponding aqueous humor. A regimen consisting of this loading dose followed by one 20 microliters drop/h for 6 h showed 45.9 +/- 3.5 micrograms/g (mean +/- SEM) in the debrided corneas and 8.8 +/- 1.7 micrograms/ml (mean +/- SEM) in the corresponding aqueous. The same regimen yielded values of 3.1 +/- 0.2 micrograms/g in the nondebrided corneas and 1.3 +/- 0.2 micrograms/ml (mean +/- SEM) in the aqueous. Minimal inhibitory concentrations (MIC) at 24 h for yeasts ranged from < 1.25 to 20 micrograms/ml, for hyaline molds from 2.5 to > 20 micrograms/ml, and dematiaceous molds from < 1.25 to > 20 micrograms/ml. Topical fluconazole exhibits pharmacokinetics and selective MICs that merit further evaluation for its ophthalmic use as a topical antifungal agent.

Administration, Topical↗
PubMed1996

Outbreak of invasive mycoses caused by Paecilomyces lilacinus from a contaminated skin lotion.

BACKGROUND: Invasive mycoses are an important cause of illness and death in immunocompromised patients. Infections with molds other than aspergilli have been increasingly seen in patients with hematologic cancers, but epidemics of these infections have not yet been reported. OBJECTIVE: To describe an outbreak of invasive mycoses with Paecilomyces lilacinus in severely neutropenic patients. DESIGN: An outbreak investigation. SETTING: The hematology-oncology isolation and bone marrow transplantation unit of the University Hospital, Basel, Switzerland. PATIENTS: 25 consecutive patients admitted between 17 August 1993 (the date of the first manifestation of P. lilacinus infection) and 31 October 1993 (when the unit was closed). MEASUREMENTS: Clinical and microbiological data, including histologic findings; cultures from several patient sites; and environmental examinations of potential airborne, parenteral, enteric, and horizontal routes of transmission. Infections were defined by the isolation of P. lilacinus from clinically evident skin eruptions. RESULTS: 12 of the 25 patients (48%) were infected or colonized. Nine patients (36%), including all bone marrow transplant recipients, had documented invasive P. lilacinus infections. All 9 infected patients had papular, pustular, or necrotic skin eruptions. Two patients with severe graft-versus-host disease died with refractory fungal disease; 1 also had microbiologically documented endophthalmitis and kidney infiltrates. Seven affected patients no longer had P. lilacinus after recovery of bone marrow function. The organism was resistant in vitro to amphotericin B, itraconazole, and fluconazole. Patients did not respond clinically to these agents. The outbreak was ultimately traced to a contaminated, commercially available, pharmaceutically prepared skin lotion. The outbreak ended after the skin lotion was recalled and has not recurred after a follow-up period of 2 years. CONCLUSION: Contaminated skin lotion is a potential cause of opportunistic fungal infections in immunocompromised hosts. Paecilomyces lilacinus is a common saprophytic mold that can cause, by direct cutaneous inoculation, invasive infections associated with illness and death.

Adolescent↗
PubMed1996

The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance.

OBJECTIVES: To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration. DESIGN: Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata. SETTING: Four tertiary care medical centers. RESULTS: Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001). CONCLUSION: In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Amphotericin B↗
PubMed1996

Phaeohyphomycosis.

Mycoses caused by dematiaceous (darkly pigmented) fungi are escalating in contemporary medicine. Such fungal infections are properly termed phaeohyphomycosis and are of increasing concern to dermatologists. A high index of suspicion, knowledge of clinical and laboratory presentations, enhanced mycologic attention, and an awareness of current therapeutic modalities--surgical and chemotherapeutic--may offer optimal management strategies for patients experiencing this type of often unique mycotic infection.

Antifungal Agents↗
PubMed1996

Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial.

The efficacy of low-dose fluconazole (200 mg orally administered thrice weekly) as primary prophylaxis for cryptococcal infection was prospectively assessed in a multicenter trial involving 218 patients who were infected with human immunodeficiency virus (HIV) and who had CD4 cell counts of < or = 100/mm3. The median CD4 cell count at baseline was 39/mm3, 58% of the patients had an AIDS-defining illness or infection prior to enrollment. Cryptococcal meningitis occurred in 0.4% (1) of the 218 patients. The breakthrough isolate was susceptible to fluconazole, and the fluconazole kinetic study demonstrated adequate drug absorption and serum fluconazole levels; noncompliance could not be excluded in this case. Mucocutaneous and/or esophageal candidiasis developed in 18% (40) of the patients. Noncompliance with fluconazole therapy was the only variable independently associated with breakthrough candidiasis in the study patients (P = .00002). Thus, fluconazole (200 mg thrice weekly) given to HIV-infected patients with CD4 cell counts of < or = 100/mm3 was efficacious as primary prophylaxis for cryptococcosis, with notably lower costs and increased convenience for patients in comparison with daily administration of the drug.

AIDS-Related Opportunistic Infections↗
PubMed1996

Detection and significance of fluconazole resistance in oropharyngeal candidiasis in human immunodeficiency virus-infected patients.

The epidemiology and clinical significance of fluconazole resistance were assessed in a cohort of advanced human immunodeficiency virus (HIV)-infected patients with recurrent oropharyngeal candidiasis. Fifty patients were prospectively evaluated using a novel method of detecting fluconazole resistance with chromogenic media containing fluconazole; results were confirmed with macrobroth testing. Resistant yeasts, defined as MICs > or = 8 micrograms/mL, were detected in 16 (32%) of 50 patients: 7 (14%) had resistant Candida albicans, 7 (14%) had resistant non-C. albicans yeast, and 2 (4%) had mixed resistant yeasts. MICs were > or = 32 in 11 of 16 isolates. Previous fluconazole use and severe immunosuppression were risk factors for resistance. However, 5 of 26 patients had resistant isolates with no prior fluconazole use, and all were severely immunosuppressed. Despite the high prevalence of resistance, 48 patients clinically responded to fluconazole. Fluconazole-resistant C. albicans and non-C. albicans yeast infections are common in patients with advanced immunodeficiency, but clinical efficacy of fluconazole remains high.

AIDS-Related Opportunistic Infections↗
PubMed1996

Microdilution antifungal susceptibility testing of Candida albicans and Cryptococcus neoformans with and without agitation: an eight-center collaborative study.

The growth patterns observed in the trailing wells when fluconazole is being tested may give rise to readings that suggest resistance or increased MICs for known susceptible strains. We conducted a multicenter study to evaluate the intralaboratory and interlaboratory reproducibilities of a method that uses agitation to disperse these types of growth. Ten strains of Candida albicans and five strains of Cryptococcus neoformans were tested against fluconazole, flucytosine, and amphotericin B by using a microdilution adaptation of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (M27-T). The endpoint criterion used before agitation was consistent with the M27-T recommendation, while a criterion of 50% or more reduction of growth compared with the control was used after agitation. The results of this study showed that use of agitation and the modified endpoint criterion both improved intralaboratory and inter-laboratory agreement and increased the frequency of interpretable MICs. The MICs obtained by this method were comparable to those obtained by the broth macrodilution M27-T method. Like M27-T, this method was not able to definitely distinguish amphotericin B-susceptible from -resistant strains, although the MICs for the resistant strains were consistently higher than those for the susceptible ones. The findings imply that agitation should be seriously considered when antifungal agents, particularly fluconazole, are tested in a microdilution format.

Amphotericin B↗
PubMed1996

Bleomycin therapy of experimental disseminated candidiasis in mice.

Bleomycin, an antineoplastic agent, was found to be very effective in vitro against a variety of fungi, including Candida albicans. Mice were infected with C. albicans intravenously and then treated with various doses of bleomycin. No efficacy was shown by either prolongation of survival or reduction of tissue counts.

Animals↗
PubMed1996

Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model.

Four strains of Candida albicans, isolated from two patients with AIDS who had undergone prolonged fluconazole therapy for oral candidiasis, were studied in a model of disseminated murine candidiasis. Pre- and posttreatment isolates from each patient were genetically related, and the fluconazole MICs for the strains had increased significantly, from 0.25 to 32 micrograms/ml for the strains isolated from patient 1 and from 1.0 to 16 micrograms/ml for the strains isolated from patient 2. Mice were infected intravenously and were treated orally with fluconazole. For survival studies, mice were treated from day 1 to day 10 postinfection and were observed through day 30. The fluconazole dosages were as follows: 0.25, 0.5, 1.0, and 5.0 mg/kg of body weight twice a day. For tissue burden studies, two groups of mice (each group received fluconazole at 0.25 or 5.0 mg/kg) were treated from day 1 to day 7 and were sacrificed 1 day later for quantitative tissue cultures of the spleen and both kidneys. For pretreatment isolates from both patients, all fluconazole dosing regimens were effective at prolonging survival compared with the survival of the control groups. For posttreatment isolates, only fluconazole at 5.0 mg/kg was effective at prolonging survival. Both fluconazole dosing regimens used in the tissue burden studies significantly reduced the counts of the pretreatment isolate from patient 1 in the spleen and kidney, while fluconazole at 5.0 mg/kg was effective at reducing the counts of the posttreatment isolate. For both isolates from patient 2, only fluconazole at 5.0 mg/kg was effective at reducing the counts in the spleen and kidney. The study indicates that C. albicans mutation to resistance to fluconazole may play a critical role in fluconazole-refractory oral candidiasis in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis.

Both animal and in vitro studies have demonstrated that combinations of flucytosine with amphotericin B and with fluconazole have significantly improved activity against cryptococcal meningitis compared with the activity of each drug used alone. However, very few dose levels of these agents have been tested in combination. This study evaluated the efficacy of fluconazole plus flucytosine in a murine model of cryptococcal meningitis over a broad range of dose combinations (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200 micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on days 2 to 11. In this highly reproducible model, fluconazole had a dramatic effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of as much as 200 micrograms/g/day alone or in combination with low doses of fluconazole had minimal fungicidal activity, whereas in combination with fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity in the range of 45 to 65% of the animals treated at doses of 40 to 100 micrograms/g/day. This striking effect of fluconazole is consistent with the results of both in vitro and clinical studies. In the clinic, the use of flucytosine is often limited by severe toxicity, while toxicity is rarely observed with fluconazole. These results suggest that when flucytosine is given with higher doses of fluconazole, the maximum therapeutic effect of the former in the clinic may be observed at dose levels that are far less than the doses commonly employed (150 micrograms/g daily).

Animals↗
PubMed1996

Systemic availability of itraconazole in lung transplantation.

Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum.

Absorption↗
PubMed1996

Cokeromyces recurvatus isolated from pleural and peritoneal fluid: case report.

The zygomycetous mold Cokeromyces recurvatus was isolated from the pleural and peritoneal fluids of a 64-year-old man with a history of peptic ulcer disease and alcohol abuse. The patient presented to the hospital with severe abdominal pain and a ruptured duodenal ulcer. This is one of the few times that C.recurvatus has been isolated from a human source, and the organism may have contributed to the death of this patient.

Alcoholism↗