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Biomedical subjects

W G Merz

Publications and source records attributed to W G Merz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of Candida dubliniensis in a prospective study of patients in the United States.

Although Candida albicans remains the fungal species most frequently isolated as an opportunistic oral pathogen, other yeast species are often identified in human immunodeficiency virus (HIV)-seropositive patients. Candida dubliniensis phenotypically resembles C. albicans in many respects, yet it can be identified and differentiated as a unique Candida species by its phenotypic and genetic profiles. The purpose of the present study was to prospectively test for the presence of C. dubliniensis among clinical isolates and to determine the clinical and demographic characteristics of patients harboring C. dubliniensis. Over a 90-day period, isolates from 724 patients that were presumptively identified as C. albicans were screened for C. dubliniensis by use of tests for germ tube and chlamydospore production, by detection of an inability to grow at 45 degrees C, by colony color on CHROMagar Candida medium, and by the results of a sugar assimilation test with the API 20C AUX yeast identification system. Among 699 isolates retrieved from those specimens evaluated, 5 from 25 HIV-seropositive patients and 1 isolate from a patient whose HIV status was unknown were shown to be consistent by phenotyping and by electrophoretic karyotyping with the European reference strain of C. dubliniensis. One of the C. dubliniensis isolates had dose-dependent susceptibility to fluconazole (MIC, 16 microg/ml). These results confirm the presence of this interesting species in the United States and support the need for further investigations into the prevalence and pathogenesis of C. dubliniensis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Coaggregation of Candida dubliniensis with Fusobacterium nucleatum.

The binding of microorganisms to each other and oral surfaces contributes to the progression of microbial infections in the oral cavity. Candida dubliniensis, a newly characterized species, has been identified in human immunodeficiency virus-seropositive patients and other immunocompromised individuals. C. dubliniensis phenotypically resembles Candida albicans in many respects yet can be identified and differentiated as a unique Candida species by phenotypic and genetic profiles. The purpose of this study was to determine oral coaggregation (CoAg) partners of C. dubliniensis and to compare these findings with CoAg of C. albicans under the same environmental conditions. Fifteen isolates of C. dubliniensis and 40 isolates of C. albicans were tested for their ability to coaggregate with strains of Fusobacterium nucleatum, Peptostreptococcus micros, Peptostreptococcus magnus, Peptostreptococcus anaerobius, Porphyromonas gingivalis, and Prevotella intermedia. When C. dubliniensis and C. albicans strains were grown at 37 degrees C on Sabouraud dextrose agar, only C. dubliniensis strains coaggregated with F. nucleatum ATCC 49256 and no C. albicans strains showed CoAg. However, when the C. dubliniensis and C. albicans strains were grown at 25 or 45 degrees C, both C. dubliniensis and C. albicans strains demonstrated CoAg with F. nucleatum. Heating the C. albicans strains (grown at 37 degrees C) at 85 degrees C for 30 min or treating them with dithiothreitol allowed the C. albicans strains grown at 37 degrees C to coaggregate with F. nucleatum. CoAg at all growth temperatures was inhibited by mannose and alpha-methyl mannoside but not by EDTA or arginine. The CoAg reaction between F. nucleatum and the Candida species involved a heat-labile component on F. nucleatum and a mannan-containing heat-stable receptor on the Candida species. The CoAg reactions between F. nucleatum and the Candida species may be important in the colonization of the yeast in the oral cavity, and the CoAg of C. dubliniensis by F. nucleatum when grown at 37 degrees C provides a rapid, specific, and inexpensive means to differentiate C. dubliniensis from C. albicans isolates in the clinical laboratory.

Amino Acids↗
PubMed1999

Recurrent, disseminated Mycobacterium marinum infection caused by the same genotypically defined strain in an immunocompromised patient.

An 81-year-old male with myasthenia gravis developed a cutaneous infection with Mycobacterium marinum, which apparently resolved following local heat therapy. Five months later, the patient developed new skin lesions and pancytopenia. M. marinum was isolated from his bone marrow. Pulsed-field gel electrophoresis was performed to determine if the skin and bone marrow isolates were clonally related. Digestion of the genomic DNA with the restriction enzymes SpeI and AseI yielded indistinguishable banding patterns. An epidemiologically unrelated control strain showed significant banding differences. The results suggest that the patient's recurrent, disseminated infection was due to recrudescence of his initial infection rather than reinfection by another strain.

Aged↗
PubMed1999

Paecilomyces lilacinus fungemia in an adult bone marrow transplant recipient.

Paecilomyces lilacinus is a rare fungal pathogen in humans. We report a case of fungemia caused by P. lilacinus in a non-neutropenic adult, 120 days after bone marrow transplant. The patient's primary risk factor was the presence of an indwelling vascular catheter. Her initial clinical course was characterized by fever, chills, and rigors. Blood cultures from the central line and peripheral veins were positive, as was a peripheral specimen drawn after removal of the catheter. Two initial peripheral specimens were positive for P. lilacinus only by blind subculture and/or sustained incubation. She developed peripheral pulmonary nodules following the fungemia, thus raising the possibility of disseminated disease, but definitive diagnosis was confounded by Pseudomonas bacteremia. The nodules cleared and she recovered following removal of the central line and treatment with amphotericin B and 5-fluorocytosine, despite in vitro resistance to these antifungal drugs. This case underscores the increasing importance of P. lilacinus as a human pathogen capable of producing disease in immunocompetent, as well as in immunocompromised hosts. Also of note is that blood culture systems may require extended incubation or subcultures in order to detect fungi.

Adult↗
PubMed1998

Resistance to amphotericin B: emerging clinical and microbiological patterns.

There has been an increasing number of reports of clinically significant amphotericin B (AmB) resistance in fungal pathogens, including Candida albicans. Concomitantly, advances in antifungal susceptibility testing have led to an improved correlation between microbiologic and clinical failure. Reports of AmB resistance, correlation of results and in vitro/in vivo correlations, mechanisms of resistance, and the transmission of resistant isolates within confined environments are reviewed. Recommendations are given regarding the clinical settings in which AmB susceptibility testing should be considered.

Journal Article↗
PubMed1998

Novel method for processing respiratory specimens for detection of mycobacteria by using C18-carboxypropylbetaine: blinded study.

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C18-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics--Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.

Bacteriological Techniques↗
PubMed1998

Specific identification of Penicillium marneffei by a polymerase chain reaction/hybridization technique.

Penicillium marneffei has been described recently as a cause of an emerging mycotic infection in HIV-infected patients. A PCR/hybridization assay was developed to rapidly identify this pathogen. The nucleotide sequence of the 631-bp region of 18S ribosomal DNA of P. marneffei was determined using the standard dideoxy chain termination method. An oligonucleotide probe was designed on the basis of the analysed sequences of P. marneffei and 18S rDNA sequences of other fungi in the GenBank database. A 631-bp PCR product was amplified using primers RRF1 and RRH1 from P. marneffei and seven other fungi, Penicillium spp., Aspergillus fumigatus, A. flavus, Histoplasma capsulatum, Cryptococcus neoformans, Candida albicans and C. krusei. A 15 oligonucleotide segment (Pm3) which was specific for P. marneffei was synthesized and used as a probe. Only the PCR products of P. marneffei isolates hybridized with the Pm3 oligonucleotide probe. The sensitivity of the assay was approximately 0.5 pg/microl and 0.1 pg/microl of DNA by PCR and Southern hybridization, respectively. The usefulness of this method as a diagnostic tool will require further studies.

AIDS-Related Opportunistic Infections↗
PubMed1997

Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.

In a case-control study to identify risk factors for fluconazole-resistant oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25 patients with clinical and in vitro fluconazole-resistant candidiasis were paired with controls who had treatment-responsive candidiasis and who had been observed for similar time periods. After their first episode of candidiasis, patients who later developed fluconazole resistance had more treated episodes than did matched controls (cases, 3.1; controls, 1.8; P = .004), lower median CD4 cell counts (11/mm3 vs. 71/mm/3; P = .004), and greater median durations of all antifungal therapy (419 vs. 118 days; P < .001) and of systemic azole therapy (272 vs. 14 days; P < .001). When paired with a second set of controls matched by CD4 cell count as well as first diagnosis of candidiasis, cases continued to show greater median exposure to azoles (272 vs. 88 days; P = .005). These data indicate that advanced immunosuppression and exposure to oral azoles are risk factors for the development of fluconazole resistance.

AIDS-Related Opportunistic Infections↗
PubMed1996

Primary invasive cutaneous Microsporum canis infections in immunocompromised patients.

Two cases of primary invasive cutaneous infections caused by the zoophilic dermatophytic species Microsporum canis are presented. The first case occurred in a liver transplant recipient who was receiving immunosuppressive therapy. Multiple erythematous papules were seen on both legs, and a biopsy revealed invasive fungal hyphae. The second case was diagnosed in a human immunodeficiency virus-positive individual with a CD4 lymphocyte count of 81 mm3. Raised red nodules were seen on her scalp and face. Histopathology was consistent with bacillary angiomatosis, and in addition, invasive septate hyphae were observed. The two strains recovered from the biopsy specimens from both individuals had colony morphologies consistent with that of M. canis, but it was difficult to induce production of macroconidia. These cases serve to increase the awareness of this unusual infection, reinforce the need for cultures, and raise some interesting questions about the potential virulence of this dermatophyte species.

AIDS-Related Opportunistic Infections↗
PubMed1995

Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum D-arabinitol.

BACKGROUND: Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis. PATIENTS AND METHODS: A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups. RESULTS: A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01). CONCLUSIONS: Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.

Candidiasis↗
PubMed1995

Detection of amphotericin B-resistant Candida isolates in a broth-based system.

Because of the limited ability of the National Committee for Clinical Laboratory Standards proposed M27P methodology to detect resistance to amphotericin B by Candida isolates, we sought to identify alternative media and pH conditions that could reliably identify resistant isolates. Antibiotic Medium 3 broth (also known as Penassay broth) buffered to pH 5 or pH 7 produced superior results and readily identified a series of resistant isolates.

Amphotericin B↗
PubMed1995

Comparison of four DNA-based methods for strain delineation of Candida lusitaniae.

Four methods for the accurate delineation of epidemiologically related and unrelated strains of Candida lusitaniae were compared. Three pulsed-field electrophoretic methods, including two contour-clamped homogeneous field gel electrophoresis methods (EKP-1 and EKP-2) yielding electrophoretic karyotype patterns of intact chromosomal DNA and a method in which the chromosomal DNA was macrodigested with the endonuclease SfiI prior to pulsed-field electrophoresis (MDP), and a random amplified polymorphic DNA (RAPD) assay were evaluated. A selected panel of 21 well-characterized isolated representing 13 strains of C. lusitaniae, including 7 epidemiologically related isolates of one strain (group I-A), 3 epidemiologically related isolates of another strain (group I-B), and 11 epidemiologically unrelated isolates (group II), were tested. All isolates were coded and tested in a blinded manner. All seven group I-A isolates were confirmed to be a single strain by the EKP-1 and MDP methods, and the three group I-B isolates were shown to be a single strain by the EKP-1, EKP-2, MDP, and RAPD methods. Subtle differences were noted with two of the group I-A isolates by the EKP-2 method, whereas three of these isolates were different by the RAPD method. Each group II isolate had distinct patterns by all four methods. These data support the fact that the three pulsed-field electrophoretic methods and the RAPD method can be used to delineate strains of C. lusitaniae. The EKP-1, EKP-2, and MDP gave results that correlated with the epidemiologic characteristics of the isolates tested in the study, whereas the RAPD method was perhaps too sensitive in detecting DNA changes for epidemiologic studies.

Candida↗
PubMed1994

In vitro evaluation of MR hypointensity in Aspergillus colonies.

PURPOSE: To demonstrate that paramagnetic elements in fungal colonies can cause hypointensity in MR images. METHODS: Aspergillus fumigatus grown in vitro was imaged with CT and MR at the time of initial inoculation and 5 days later. CT and MR images, T2 values, scanning electron microscopy, energy-dispersive analysis, and furnace atomic absorption spectrometry were performed. RESULTS: After 5 days of growth, MR images of A fumigatus revealed curvilinear hypointensities on T2-weighted images corresponding to the fungal growth. Gradient-echo images revealed two distinct components of hypointensity with different calculated T2 values. Phase-angle-difference images revealed a phase shift characteristic of magnetic-susceptibility paramagnetic effects, which corresponded to the hypointense regions on gradient-echo images. Energy-dispersive analysis and furnace atomic absorption spectrometry confirmed the presence of paramagnetic elements. CONCLUSION: It was shown that in vitro A fumigatus concentrates metal elements contained within the nutrient broth. These focal collections of calculated T2 values are caused at least partly by magnetic susceptibility effects.

Aspergillus↗
PubMed1993

Response to antifungal therapy by human immunodeficiency virus-infected patients with disseminated Penicillium marneffei infections and in vitro susceptibilities of isolates from clinical specimens.

Eighty-six patients with laboratory evidence of human immunodeficiency virus infection presented to Chiang Mai University Hospital in Chiang Mai, Thailand, between 1 June 1990 and 30 June 1992 with systemic infection caused by the dimorphic fungus Penicillium marneffei. Thirty isolates of P. marneffei from clinical specimens from these patients were tested for their in vitro susceptibilities to amphotericin B, 5-fluorocytosine, miconazole, ketoconazole, itraconazole, and fluconazole. P. marneffei was highly susceptible to miconazole, itraconazole, ketoconazole, and 5-fluorocytosine. Amphotericin B showed intermediate antifungal activity, while fluconazole was the least active; some strains of the fungus were resistant to fluconazole. The clinical and microbiological responses correlated with the overall patterns of in vitro susceptibility to the azoles, whereas results with amphotericin B were more difficult to assess. Antibiotic failures of initial therapy occurred in 8 of 35 (22.8%) patients treated with amphotericin B, 3 of 12 (25%) patients treated with itraconazole, and 7 of 11 (63.6%) patients treated with fluconazole. Itraconazole or ketoconazole should be considered to be the drug of first choice in the treatment of mild to moderately severe P. marneffei infection. Parenteral therapy with amphotericin B may be required for seriously ill patients. Since at least 12 patients who responded to initial therapy relapsed within 6 months regardless of initial antifungal therapy, maintenance oral therapy with itraconazole or ketoconazole may be necessary.

Acquired Immunodeficiency Syndrome↗