Biomedical subjects

D A Sutton

Publications and source records attributed to D A Sutton.

At least 37 records · Page 2Linked to original sources

PubMed2000

Comparison of high-performance liquid chromatographic and microbiological methods for determination of voriconazole levels in plasma.

A new selective high-performance liquid chromatography (HPLC) method with UV detection for the determination of the investigational triazole voriconazole in human plasma by using acetonitrile precipitation followed by reverse-phase HPLC on a C(18) column was compared with a simple agar well diffusion bioassay method with Candida kefyr ATCC 46764 as the assay organism. Pooled plasma was used to prepare standard and control samples for both methods. The results of analyses with spiked serum samples (run as unknowns) were concordant by the bioassay and HPLC methods, with expected values being obtained. HPLC demonstrated an improved precision (3.47 versus 12.12%) and accuracy (0.81 versus 1.28%) compared to those of the bioassay method. The range of linearity obtained by both methods (from 0.2 to 10 microg/ml for HPLC and from 0.25 to 20 microg/ml for the bioassay) includes the range of concentrations of voriconazole (from 1.2 to 4.7 microg/ml) which are considered clinically relevant. Although either methodology could be used for the monitoring of patient therapy, the smaller variability observed with HPLC compared to that observed with the bioassay favors the use of HPLC for pharmacokinetic studies.

Antifungal Agents↗

PubMed2000

Pulmonary infection caused by Gymnascella hyalinospora in a patient with acute myelogenous leukemia.

We report the first case of invasive pulmonary infection caused by the thermotolerant ascomycetous fungus Gymnascella hyalinospora in a 43-year-old female from the rural midwestern United States. The patient was diagnosed with acute myelogenous leukemia and treated with induction chemotherapy. She was discharged in stable condition with an absolute neutrophil count of 100 cells per microliter. Four days after discharge, she presented to the Cancer Clinic with fever and pancytopenia. A solitary pulmonary nodule was found in the right middle lobe which was resected by video-assisted thoracoscopy (VATHS). Histopathological examination revealed septate branching hyphae, suggesting a diagnosis of invasive aspergillosis; however, occasional yeast-like cells were also present. The culture grew a mold that appeared dull white with a slight brownish tint that failed to sporulate on standard media. The mold was found to be positive by the AccuProbe Blastomyces dermatitidis Culture ID Test (Gen-Probe Inc., San Diego, Calif.), but this result appeared to be incompatible with the morphology of the structures in tissue. The patient was removed from consideration for stem cell transplant and was treated for 6 weeks with amphotericin B (AmB), followed by itraconazole (Itr). A VATHS with biopsy performed 6 months later showed no evidence of mold infection. In vitro, the isolate appeared to be susceptible to AmB and resistant to fluconazole and 5-fluorocytosine. Results for Itr could not be obtained for the case isolate due to its failure to grow in polyethylene glycol used to solubilize the drug; however, MICs for a second isolate appeared to be elevated. The case isolate was subsequently identified as G. hyalinospora based on its formation of oblate, smooth-walled ascospores within yellow or yellow-green tufts of aerial hyphae on sporulation media. Repeat testing with the Blastomyces probe demonstrated false-positive results with the case isolate and a reference isolate of G. hyalinospora. This case demonstrates that both histopathologic and cultural features should be considered for the proper interpretation of this molecular test and extends the list of fungi recognized as a cause of human mycosis in immunocompromised patients.

Adult↗

PubMed2000

Microascus cinereus (Anamorph scopulariopsis) brain abscess in a bone marrow transplant recipient.

We report the first documented case of brain abscess due to the dematiaceous fungus Microascus cinereus, an organism common in soil and stored grain. M. cinereus was isolated from brain abscess material from a bone marrow transplant recipient. The patient responded well to treatment by amphotericin B lipid complex, itraconazole, and a craniotomy but later died from secondary complications caused by graft-versus-host disease.

Adult↗

PubMed2000

Acrophialophora fusispora brain abscess in a child with acute lymphoblastic leukemia: review of cases and taxonomy.

A 12-year-old girl with acute lymphoblastic leukemia was referred to King Faisal Specialist Hospital and Research Center. The diagnosis without central nervous system (CNS) involvement was confirmed on admission, and chemotherapy was initiated according to the Children Cancer Group (CCG) 1882 protocol for high-risk-group leukemia. During neutropenia amphotericin B (AMB) (1 mg/kg of body weight/day) was initiated for presumed fungal infection when a computed tomography (CT) scan of the chest revealed multiple nodular densities. After 3 weeks of AMB therapy, a follow-up chest CT revealed progression of the pulmonary nodules. The patient subsequently suffered a seizure, and a CT scan of the brain was consistent with infarction or hemorrhage. Because of progression of pulmonary lesions while receiving AMB, antifungal therapy was changed to liposomal AMB (LAMB) (6 mg/kg/day). Despite 26 days of LAMB, the patient continued to have intermittent fever, and CT and magnetic resonance imaging of the brain demonstrated findings consistent with a brain abscess. Aspiration of brain abscess was performed and the Gomori methenamine silver stain was positive for hyphal elements. Culture of this material grew Acrophialophora fusispora. Lung biopsy showed necrotizing fungal pneumonia with negative culture. The dosage of LAMB was increased, and itraconazole (ITRA) was added; subsequently LAMB was discontinued and therapy was continued with ITRA alone. The patient demonstrated clinical and radiological improvement. In vitro, the isolate was susceptible to low concentrations of AMB and ITRA. A. fusispora is a thermotolerant, fast-growing fungus with neurotropic potential. We report the first case of human infection involving the CNS. Acrophialophora resembles Paecilomyces but differs in having colonies that become dark and in the development of phialides along the sides or at the tips of echinulate brown conidiophores. Conidia are borne in long chains and are smooth or ornamented with fine-to-coarse echinulations, sometimes in spiral bands. The taxonomy of the genus Acrophialophora is reviewed, and Acrophialophora nainiana and Acrophialophora levis are considered as synonyms of A. fusispora.

Brain Abscess↗

PubMed2000

Bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus.

A case of bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus is described. The diagnosis was established by the presence of septate, dichotomously branched fungal elements in freshly collected bronchoalveolar lavage and sputum specimens and by repeated isolation of the fungus in culture. Specific precipitating antibodies against the A. terreus isolate were demonstrated in the patient's serum. The isolate was atypical as it failed to produce fruiting structures on routine mycological media, but it did so on extended incubation on potato flake agar and produced globose, relatively heavy-walled, hyaline accessory conidia (formerly termed aleurioconidia) on both vegetative and aerial mycelia. Also, it produced an intense yellow diffusing pigment in the medium. The report underscores the increasing importance of A. terreus in the etiology of pulmonary aspergillosis. It is suggested that A. terreus antigen be included in the battery of serodiagnostic reagents to facilitate the early diagnosis of infections caused by this species.

Adult↗

PubMed2000

Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute myelogenous leukemia.

Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola.

Dermatomycoses↗

PubMed1999

Metarrhizium anisopliae as a cause of sinusitis in immunocompetent hosts.

Metarrhizium anisopliae is a common pathogen of insects and has even been used to control insect populations. It is rarely isolated from human or animal sources, but recently, there have been three reported cases of disease, two in humans and one in a cat. We present our experience with five isolates from human sources, including two that were the apparent causes of two cases of sinusitis in immunocompetent hosts. The first patient was a 36-year-old male with frontal and ethmoid sinusitis, and the second was a 79-year-old female with chronic sinusitis. Both patients underwent surgery, and pathology of the surgical specimens revealed branching hyphae. Cultures grew only Metarrhizium species. Neither patient received antifungal therapy, and both did well postoperatively. The other three isolates were cultured from bronchoalveolar lavage specimens but were not felt to be clinically significant. Antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards macrobroth method revealed that all isolates were resistant to amphotericin B, 5-flucytosine, and fluconazole. Itraconazole and newer azole compounds were more active. Metarrhizium species may cause disease in humans, even those without evidence of immunosuppression, and are apparently highly resistant to amphotericin B in vitro.

Adult↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

Disseminated zygomycosis due to Rhizopus schipperae after heatstroke.

A 21-year-old woman suffered heatstroke and developed diarrhea while trekking across south Texas. The heatstroke was complicated by seizures, rhabdomyolysis, pneumonia, renal failure, and disseminated intravascular coagulation. The patient's stool and blood cultures grew Campylobacter jejuni. The patient subsequently developed paranasal and gastrointestinal zygomycosis and required surgical debridement and a prolonged course of amphotericin B. The zygomycete cultured was Rhizopus schipperae. This is only the second isolate of R. schipperae that has been described. R. schipperae is characterized by the production of clusters of up to 10 sporangiophores arising from simple but well-developed rhizoids. These asexual reproductive propagules are produced on Czapek Dox agar but are absent on routine mycology media, where only chlamydospores are observed. Despite multiorgan failure, bacteremia, and disseminated zygomycosis, the patient survived and had a good neurological outcome. Heatstroke has not been previously described as a risk factor for the development of disseminated zygomycosis.

Adult↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation.

The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described. The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation. She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl. Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge. Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500. Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus. The patient was placed on ganciclovir. A biopsy specimen from a leg lesion also noted on day 67 p.t. revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus. Confirmation detection of A. ustus was made by demonstration of characteristic reproductive structures with the presence of Hülle cells. On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated. The patient's condition worsened, and she died 79 days p.t. At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A. ustus. In vitro susceptibility testing indicated probable resistance to AMB but not to ITR. This case supports the need for the development of rapid methods to determine antifungal susceptibility.

Aspergillosis↗

PubMed1998

U.S. case report of cerebral phaeohyphomycosis caused by Ramichloridium obovoideum (R. mackenziei): criteria for identification, therapy, and review of other known dematiaceous neurotropic taxa.

We report a case of cerebral phaeohyphomycosis in a 36-year-old male caused by the neurotropic fungus Ramichloridium obovoideum (Matushima) de Hoog 1977 (Ramichloridium mackenziei Campbell et Al-Hedaithy 1993). This man resided in the Middle East, where the fungus appears to be endemic and, possibly, geographically restricted, since all previous reports of brain abscesses due to this organism have been for patients indigenous to this area. As a servant of the Saudi Arabian royal family, he appeared in the United States seeking treatment for chronic weight loss, fatigue, decreased memory, and a more recent 2-week history of right-hand weakness which worsened to involve the entire right upper extremity. On the day prior to his admission, he had a focal motor seizure with rotation of the head and eyes to the right, followed by secondary generalization. A computerized tomogram showed a ring-enhancing hypodense lesion in the left parietal subcortical region with associated edema and mass effect. Diagnosis of a fungal etiology was made following a parietal craniotomy and excisional biopsy by observation of septate, dematiaceous hyphal elements 2 to 3 microm in width on hematoxylin-and-eosin-stained sections from within areas of inflammation and necrosis. Culture of the excised material grew out a dematiaceous mould which was subsequently identified as R. obovoideum. At two months postsurgery and with a regimen of 200 mg of itraconazole twice a day, the patient was doing well and returned to Saudi Arabia. His condition subsequently deteriorated, however, and following a 7-month course of itraconzole, he expired. We use this case to alert clinicians and personnel in clinical mycology laboratories of the pathogenicity of this organism and its potential occurrence in patients with central nervous system signs and symptoms who have resided in the Middle East and to review and/or compare R. obovoideum with other neurotropic, dematiaceous taxa and similar nonneurotropic, dematiaceous species.

Adult↗

PubMed1998

Fatal Hormonema dematioides peritonitis in a patient on continuous ambulatory peritoneal dialysis: criteria for organism identification and review of other known fungal etiologic agents.

We report a fatal case a fungal peritonitis caused by the yeast-like dematiaceous mould Hormonema dematioides in a 45-year-old woman. The woman had a 13-year history of insulin-dependent diabetes mellitus and had been on continuous ambulatory peritoneal dialysis for chronic renal failure. H. dematioides was repeatedly isolated from the dialysate culture specimens collected on days 3, 9, 16, and 20 of her hospital stay. Preliminary culture reports on day 7 of the growth of a yeast-like fungus, a probable Candida species, prompted the administration of fluconazole (FLU). Intraperitoneal and intravenous FLU failed to eliminate the mould, and the patient expired on day 21 of her hospital stay. We use this case to present what appears to be the first report of fungal peritonitis due to H. dematioides, to provide laboratorians with criteria for differentiating this organism from the similar mould Aureobasidium pullulans and from various yeast genera, and to provide a review of known fungal taxa inciting peritonitis.

Ascitic Fluid↗

PubMed1998

In vitro activity of voriconazole against selected fungi.

Fifty-nine isolates consisting of 14 genera and 33 species of ascomycetes, basidiomycetes, and zygomycetes were tested against amphotericin B, fluconazole, itraconazole and voriconazole using an in vitro modified macrobroth dilution procedure based upon the NCCLS M27-A standard method for yeasts. The triazoles voriconazole and itraconazole had similar MIC values, except for Acremonium alabamensis, A. strictum, Fusarium oxysporum, F. solani and Wangiella dermatitidis, which had substantially lower voriconazole MIC values. Voriconazole MIC values were lower than those for itraconazole for the 17 species of Trichosporon tested. Fluconazole had high MIC values, often greater than 128 microg ml-1.

Amphotericin B↗

PubMed1997

In vitro evaluation of voriconazole against some clinically important fungi.

Voriconazole was compared to amphotericin B, fluconazole, and itraconazole by using an in vitro macrobroth dilution test based upon current National Committee for Clinical Laboratory Standards tentative standards against the dimorphic fungi and several opportunistic molds and yeasts. In all instances, the voriconazole MICs were lower than those of fluconazole. In most instances, the MICs were lower than the recorded MICs of amphotericin B and itraconazole.

Antifungal Agents↗