Biomedical subjects

Stanley W Chapman

Publications and source records attributed to Stanley W Chapman.

8 recordsLinked to original sources

PubMed2005

Thrombocytosis during antifungal therapy of candidemia.

BACKGROUND: Secondary, "reactive," thrombocytosis has been attributed to bacterial infection and treatment with multiple pharmaceuticals and may be associated with an increase in the incidence of gastrointestinal tract bleeding and thrombotic events (eg, stroke). OBJECTIVE: To characterize the dynamics of thrombocytosis in patients with candidemia receiving antifungal therapy. METHODS: We initiated a retrospective observational description of patients with candidemia who were treated with antifungal agents. A total of 108 patients diagnosed with candidemia between August 1995 and September 2003 at our teaching hospital were enrolled. Three groups (candidemia with antifungal therapy, candidemia without antifungal therapy, antifungal therapy without candidemia) of patients >18 years of age were evaluated for the presence of thrombocytosis. Platelet administration, pharmacologic or pathologic contributors to thrombocytosis, and other pertinent details related to an elevation of platelet counts were scrutinized. RESULTS: Reactive thrombocytosis was observed in approximately 10% of treated patients with candidemia. Within the subgroup developing reactive thrombocytosis, life-threatening thrombotic complications were uncommon. Mean baseline platelet counts were 393 x 10(3)/mm3, with a mean peak (695 x 10(3)/mm3) occurring an average of 13 days after initiation of therapy. All patients had resolution within 7 days after therapy. The maximum peak (1056 x 10(3)/mm3) was observed in a patient after 14 days of antifungal therapy. The onset of thrombocytosis in this patient was 4 days and lasted 4 days after therapy. CONCLUSIONS: Reactive thrombocytosis occurs during treatment of candidemia. The causative agent (drug vs disease), the risk associated with this reaction, and evaluation of treatment need to be elucidated by a larger epidemiologic study or controlled, prospective clinical trial.

Adolescent↗

PubMed2003

A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

Adult↗

PubMed2003

Blastomycosis.

Blastomycosis is an endemic mycoses in the central United States caused by a dimorphic fungus, Blastomyces dermatitidis, that exists in nature in mycelial phase and converts to yeast phase at body temperature. The organism may produce epidemics of infection following a point source of infection or sporadic endemic infection. Blastomycosis can be a subclinical illness with subsequent protection against progressive infection afforded by cellular immune mechanisms, but it may present with progressive disease with either pulmonary or extrapulmonary disease or both. Itraconazole has been shown to be the drug of choice for both infections, except in cases of life-threatening infection when amphotericin B should be used.

Blastomyces↗

PubMed2003

Voriconazole: a new triazole antifungal agent.

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

Antifungal Agents↗

PubMed2003

Variability in polyene content and cellular toxicity among deoxycholate amphotericin B formulations.

STUDY OBJECTIVE: To evaluate the toxicity of amphotericin B deoxycholate formulations. DESIGN: In vitro experiment. SETTING: University research center. MATERIAL: Human mononuclear THP-1 cells. INTERVENTION: The human mononuclear cells were exposed in vitro for 2 hours to the following deoxycholate formulations of amphotericin B, in 2.5- and 5-micro/ml concentrations: Apothecon, Pharmacia, Sigma, Gensia, Pharma-Tek, and VHA. MEASUREMENTS AND MAIN RESULTS: Toxicity of the amphotericin B formulations were assessed by measuring interleukin (IL)-1beta expression in an in vitro model. Amphotericin B content was measured by enzyme-linked immunosorbent assay (ELISA), and amphotericin A and B contents were assessed by spectrophotometry. Endotoxin contamination was evaluated in all reagents. Expression of IL-1beta from Sigma, Pharmacia, and Pharma-Tek formulations was increased approximately 250%, 50%, and 25%, respectively, compared with amphotericin A. Amphotericin B content of Sigma, Pharmacia, Pharma-Tek, and Gensia formulations, as measured by ELISA, was increased approximately 450%, 200%, 200%, and 100%, respectively, compared with Apothecon. This variation could not be explained by differences in amphotericin A or B content as measured by spectrophotometry. CONCLUSION: Amphotericin B is obtained from a fermentation plant and manufactured as a pharmaceutical at different facilities. Both previous clinical observations and the current in vitro evaluation revealed significant differences among the formulations. Likely, other polyenes or pyrogenic toxins in differing amounts are in these formulations, thus explaining the variability in toxicity observed among the formulations.

Amphotericin B↗

PubMed2003

Effects of amphotericin B and caspofungin on histamine expression.

STUDY OBJECTIVE: To determine the effects of amphotericin B deoxycholate and caspofungin on the release of histamine from human peripheral blood cells, mononuclear cells, and mast cells. DESIGN: In vitro cell culture experiments. SETTING: University medical center. MATERIAL: Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers. MEASUREMENTS AND MAIN RESULTS: The cultured cells were incubated with increasing concentrations of amphotericin B deoxycholate, diphenhydramine, amphotericin B deoxycholate plus diphenhydramine, caspofungin, caspofungin plus diphenhydramine, and the calcium ionophore A23187 for up to 24 hours. Histamine concentrations and histamine N-methyltransferase activity were determined at various time points throughout exposure. Cell viability was assessed by exclusion of erythrocin B. The A23187 increased histamine concentrations from baseline in peripheral blood and HMC-1 cells. No change in histamine concentrations was observed in response to amphotericin B deoxycholate, whereas caspofungin induced a significant increase in histamine release in peripheral blood cells and HMC-1 cells. No change in histamine concentrations was observed in THP-1 cells in response to any pharmacologic agent tested. Similarly, histamine N-methyltransferase activity in peripheral blood was not affected by amphotericin B deoxycholate, but was significantly decreased by caspofungin. CONCLUSION: Amphotericin B deoxycholate does not affect histamine concentrations or histamine N-methyltransferase activity in whole blood or HMC-1 cells, suggesting that the amphotericin B-induced infusion-related reaction is not a histamine-mediated event. Conversely, caspofungin increased histamine concentrations in whole blood and HMC-1 cells and inhibited histamine N-methyltransferase activity. These data suggest that infusion-related reactions associated with caspofungin may be mediated by histamine release secondary to caspofungin.

Amphotericin B↗

PubMed2002

Differential expression of genes encoding immunomodulatory proteins in response to amphotericin B in human mononuclear cells identified by cDNA microarray analysis.

Amphotericin B (AMB) is an antifungal agent that possesses immunomodulatory properties that may contribute to its infusion-related toxicity and activity. It has previously been shown to induce the expression of genes encoding the cytokines interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha and the chemokines IL-8 and macrophage inflammatory protein (MIP)-1 beta in the human monocytic cell line THP-1. In an effort to identify additional AMB-responsive genes, the gene expression profiles of both THP-1 cells and human peripheral blood mononuclear cells (hPBMCs) on exposure to AMB were assessed using cDNA microarray analysis. In addition to genes known to be AMB responsive, we found the genes encoding IL-1 alpha and MIP-1 alpha to be AMB responsive in both THP-1 cells and hPBMCs. Increases in MIP-1 alpha and MIP-1 beta were also observed in the supernatants of hPBMCs exposed to AMB. The expression of several genes in response to AMB was unique to either cell type. Furthermore, variability in gene expression in hPBMCs was observed between donors. These genes and respective gene products may have significance in the infusion-related toxicity and activity of AMB.

Adjuvants, Immunologic↗

PubMed2002

Necrotizing fasciitis of the upper extremity resulting from a water moccasin bite.

Aeromonas hydrophila infection has been described as the cause of necrotizing fasciitis in patients with suppressed immune systems, burns, or trauma in an aquatic setting. We report a case in which severe necrotizing fasciitis involving hand, arm, chest, and lateral side of trunk, along with toxic shock, developed after the patient was bitten by a venomous snake. Mixed aerobic and anaerobic bacteria, including A hydrophila, were isolated from the wound culture. The patient was treated with antivenom, a diuretic regimen, broad spectrum antibiotics, and 18 separate surgical procedures. After the application of skin grafts, the wound completely healed. This case illustrates that a venomous snakebite may result in infection with A hydrophila and can cause severe necrotizing fasciitis. Early and aggressive surgical intervention should be implemented as soon as the necrotizing fasciitis is diagnosed.

Adult↗