Biomedical subjects
Publications and source records attributed to Deanna A Sutton.
An analytical method for the determination of voriconazole (UK-109,496; Pfizer) in plasma was developed and validated. The method utilizes solid-phase extraction technology and high-performance liquid chromatography. The lower limit of quantitation is 0.2 microg/ml, and the range of linearity tested was 0.2 to 10 microg/ml.
BACKGROUND: Numerous organisms have been identified in dental unit waterlines, or DUWLs. Decontamination of DUWLs focuses on maintaining heterotrophic, mesophilic bacteria below 200 colony-forming units per milliliter as recommended by the ADA. METHODS: The authors conducted a study to test the efficacy of a continuous-use, stabilized chlorine dioxide proprietary compound to decrease the number of bacteria in DUWLs. The authors used three dental units with self-contained water systems to test the product and three similar units as controls. They aseptically collected water samples weekly according to recommended methods, plated the samples on R2A agar and incubated them for seven days. RESULTS: The authors isolated heterotrophic, mesophilic bacteria from treatment and control units for eight weeks. In the ninth week, the predominant isolates from one of the treatment units changed in appearance to small, dark, shiny colonies that the authors tentatively identified as fungal. The authors then isolated similar colonies from the source tap water and ultrasonic and handpiece lines. They added three additional dental units from the same clinic in the sixth week of the study and isolated similar fungal colonies from them after five weeks of treatment. The authors performed DNA sequencing with an automated sequencer and identified the organism Exophiala mesophila. CONCLUSIONS: The authors did not observe fungal isolates in the control units, which suggests that continuous waterline treatment may cause proliferation of a fungus present in small amounts in source water. CLINICAL IMPLICATIONS. The findings of this study indicate the need to monitor water quality regularly when treating waterlines with continuous-use chemical cleaners.
Pharmacokinetic studies of antifungal agents in reptiles are uncommon. Itraconazole, which has been used prophylactically in juvenile sea turtles suffering from hypothermia (cold stunning) on a regular basis, was evaluated for steady-state plasma concentrations. Five Kemp's ridley sea turtles (Lepidochelys kempi) receiving itraconazole at several dosages in a rehabilitation program had blood collected within 24 hr to estimate dosing frequency. Subsequently, serial blood samples of Kemp's ridley sea turtles that were given itraconazole at several dosages for 30 days to treat cold stunning were collected at various intervals to evaluate itraconazole plasma concentrations. Tissue samples were collected from one Kemp's ridley that died during rehabilitation. Plasma concentrations of itraconazole (and of hydroxyitraconazole [OH-ITRA], one of its major bioactive metabolites) were determined using a modified, validated reverse-phase high-performance liquid chromatography technique. Itraconazole concentrations in tissues were determined by bioassay to be far greater than the plasma concentrations measured in any of the turtles. At a 15-mg/kg dosage, the half-life (t1/2) was 75 hr for itraconazole and 55 hr for OH-ITRA. All dosages produced adequate concentrations in some turtles, but consistent therapeutic concentrations were produced only at 15 mg/kg q72hr and 5 mg/kg s.i.d., with the latter producing the highest plasma concentrations.
Paecilomyces lilacinus, an environmental mold found in soil and vegetation, rarely causes human infection. We report the first case of P. lilacinus isolated from a vaginal culture in a patient with vaginitis.
From December 1996 through September 1997, we diagnosed 19 cases of fungemia due to Exophiala jeanselmei. We conducted a matched case-control study in which we cultured specimens of blood products, intravenous solutions, and water from a hospital water system. Isolates from environmental cultures were compared to those recovered from patients by random amplification of polymorphic DNA (RAPD). Multivariate analysis showed that neutropenia, longer duration of hospitalization, and use of corticosteroids were risk factors for infection. Environmental cultures yielded E. jeanselmei from 3 of 85 sources: deionized water from the hospital pharmacy, 1 water tank, and water from a sink in a non-patient care area. Use of deionized pharmacy water to prepare antiseptic solutions was discontinued, and no additional cases of infection occurred. RAPD typing showed that isolates from case patients and isolates from the pharmacy water were highly related, whereas the patterns of isolates recovered from the 2 other sources of water were distinct.
Disseminated phaeohyphomycosis is an uncommon infection caused by dematiaceous fungi, although the number of case reports about this infection has been increasing in recent years. A total of 72 cases are reviewed. Scedosporium prolificans is by far the most common cause. The presence of melanin in their cell walls may be a virulence factor for these fungi. The primary risk factor is decreased host immunity, although cases in apparently immunocompetent patients have been reported. Eosinophilia was seen in 11% of cases. Endocarditis is mostly reported on bioprosthetic valves, particularly those of porcine origin. The outcome of antifungal therapy remains poor, with an overall mortality rate of 79%. Special precautions taken for immunocompromised patients may help prevent exposure to fungi during the patients' period of greatest risk. The development of newer antifungal agents and combination therapy may hold promise in improving the management of these devastating infections in the future.
PURPOSE OF REVIEW: An increase in refractory invasive fungal infections in the setting of marrow/solid organ transplantation and other immune-compromising clinical entities has provided the impetus for the development of new, more efficacious/less toxic antifungal agents. This review (1) examines currently available laboratory methods for the in-vitro evaluation of these new agents against both yeasts and filamentous fungi; (2) provides a summary of the most attractive investigational agents currently undergoing clinical trials/development; and (3) outlines the major refractory mycoses in contemporary medicine. RECENT FINDINGS: Fluconazole-resistant Candida spp., Trichosporon spp., zygomycetous genera, the endemic mycoses, Scedosporium, Aspergillus, and Fusarium spp., and an ever-expanding list of lesser-known hyaline and phaeoid genera inciting invasive fungal infections comprise the bulk of refractory mycoses in the immune-compromised host. In-vitro data generated from reference-based antifungal susceptibility testing methods indicate an increased armamentarium of potentially efficacious agents against most of these mycoses. SUMMARY: The newly approved antifungal agents caspofungin and voriconazole, used either as monotherapy or in combination regimens, have a significantly improved spectrum of activity over previously available therapeutic options. Correlation of clinical outcomes with investigational agents demonstrating in-vivo/in-vitro activity will provide critical information needed for the development of clinically significant minimum inhibitory concentration interpretative breakpoints.
(Sca) is a ubiquitous filamentous fungus capable of causing invasive disease. We reviewed our electronic microbiology records and the English-language literature. Between 1976 and December 1999 we identified 23 solid organ transplant recipients with Sca infection, 7 of which occurred between December 1987 and December 1999 at our institution. Overall incidence was 1 per 1,000 patients, with a trend of higher incidence in patients receiving lung transplants compared with other transplant organs (p = 0.06). The 23 patients included liver (4), kidney (8), heart (8), lung (2), and heart/lung (1) recipients. Male to female ratio was 19:4, and the mean age was 46 +/- 12 (SD) years. Fungal infection was diagnosed at a median of 4 months (range, 0.4-156 mo) after transplant. The clinical presentation included disseminated disease ( 8), skin lesions (3), lung disease (5), endophthalmitis (1), meningitis (1), brain abscess with or without extension to eye (3), fungal mycotic aneurysm (1), and sinusitis (1). Seven (30%) patients had intravascular infection, and 11 (48%) patients had central nervous system involvement. Antifungal therapy was accompanied by surgical debridement in 9 cases. Three additional patients were found to have airway colonization only and received itraconazole prophylaxis, without evidence of disease. Of 22 patients with known outcome, 16 (72.7%) died. Five of 6 patients who survived had localized infections: skin lesions (n = 3), sinus fungus ball (n = 1), and solitary lung nodule (n = 1). All patients with disseminated disease and 10 of 11 patients with central nervous system disease died. An exception was 1 patient with a brain abscess, successfully treated with voriconazole and surgical drainage. Sca infection is rare but is associated with high mortality. Early diagnosis by culture is important because Sca is resistant to amphotericin B, routinely used in the empiric therapy of invasive fungal infections. Treatment with the combination of an antifungal and surgery may have a better outcome. Voriconazole promises to be an effective antifungal agent. Cultures positive for Sca should not be ignored, and long-term antifungal prophylaxis in candidates and transplant recipients should be considered.
We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis.
Colletotrichum acutatum is a cosmopolitan plant pathogen with a wide host range. While the organism's phytopathogenic potential has been well documented, it has never been reported as an etiologic agent of disease in either animals or humans. In this case, a juvenile Kemp's ridley sea turtle, Lepidochelys kempi, probably with immune compromise following cold stunning (extended hypothermia), developed a disseminated mycotic infection in the lungs and kidneys. Prophylactic treatment with oral itraconazole did not prevent or cure the infection. This report of a Colletotrichum acutatum infection in an animal extends the range of disease caused by this organism beyond that of a phytopathogen.
A checkerboard microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was used to study the in vitro interaction of terbinafine (TRB) with fluconazole (FLU), itraconazole (ITRA), voriconazole (VRC), and posaconazole (PSZ) in 24 isolates of Candida glabrata with decreased susceptibility to azoles isolated from the oral cavities of human immunodeficiency virus patients. Synergy, defined as a fractional inhibitory concentration index of < or =0.5, was observed in 17% of TRB-FLU interactions, 21% of TRB-ITRA interactions, 33% of TRB-VRC interactions, and 12% of TRB-PSZ interactions. Where synergy was not achieved, there was still a decrease in the MIC of one or both drugs when used in combination. Antagonism was not observed in any drug combination. Clinical studies are warranted to elucidate the potential utility of these combination therapies.
Phialemonium species are grouped by most authorities among the dematiaceous fungi. Like several other darkly pigmented fungi, they appear to be an emerging cause of human disease, especially in the immunocompromised host. As numbers of immunocompromised patients increase, the trend of unusual fungi emerging as new pathogens is set to continue. Previous experience suggests that reports of rare fungal infections among selected patients often heralds the emergence of infection in a wider population of patients. We report a case of fatal endocarditis caused by Phialemonium obovatum in a premature neonate. To our knowledge this is the first documented case of native valve endocarditis due to this species, and we review the literature on invasive disease caused by the species. Unfamiliar fungal isolates are frequently misidentified or mistaken for environmental contaminants, and because of their relative rarity, data upon which to base antifungal treatment are limited. Thus, the diagnosis and treatment of unusual fungal pathogens present a significant challenge to clinicians and microbiologists alike. Early referral of such isolates to a specialist reference laboratory is advisable.
Explore the source record for details and available documents.