Anaphylaxis upon switching lipid-containing amphotericin B formulations.
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Biomedical subjects
Publications and source records attributed to C A Kauffman.
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Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has been linked to the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). To date, direct visualization of the virus in a clinical sample has not been demonstrated. We have performed an extensive clinical, histologic, immunophenotypic, ultrastructural, and molecular genetic correlative study on multiple tissue samples obtained premortem and at autopsy from an patient with AIDS with Kaposi's sarcoma and body cavity-based lymphomas. We demonstrate the presence of human herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular level, as well as document multiple lymphomatous tumor masses at autopsy.
OBJECTIVES: To assess colonization and serious infection with yeasts and the risk factors that are associated with colonization by these organisms. DESIGN: Monthly surveillance for colonization and infection over a period of 2 years. SETTING: A long-term-care facility (LTCF) attached to an acute-care Veterans Affairs Medical Center. PARTICIPANTS: The 543 men and 10 women in the facility. MEASUREMENTS: Colonization and serious infection rates with yeasts. Analysis of risk factors associated with yeast colonization of residents. RESULTS: Colonization rates were relatively stable during the 2-year period (53+/-1.8% patients colonized per month). Candida albicans was the most common colonizer, found in 35+/-.9% of patients colonized per month. The pharynx was the most commonly colonized site, with 41+/-1.4% of patients per month with pharyngeal colonization. Eighty-four percent of patients remaining in the facility for 3 or more months were colonized by yeast at some time during their stay. Presence of neurogenic bladder, leg amputation, or a low serum albumin were independently associated with yeast colonization; neither diabetes mellitus nor functional status was a risk factor for colonization by yeasts. Only four serious yeast infections in four patients (esophagitis and three urinary tract infections) were found during the 2-year period; all infections occurred in patients who were colonized by yeasts previously. CONCLUSION: In our LTCF, colonization of patients by yeasts occurred commonly in those residents remaining in the facility for 3 or more months. However, serious yeast infections occurred infrequently. It is likely that colonization of residents of LTCFs by yeasts may only become clinically important when the patient is transferred to an acute-care hospital where additional risk factors may allow the development of serious yeast infection.
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This article reviews the clinical manifestations, diagnosis and management of some of the more important systemic infections that are now being imported into Europe. It also considers the risks some of the causal organisms pose to European laboratory workers, many of whom are unfamiliar with the precautions that should be taken when handling these pathogens.
OBJECTIVE: The steady-state kinetics of delavirdine and desisopropyldelavirdine were evaluated in human immunodeficiency virus-positive patients after escalating oral doses and after repeated oral administrations at the same dose level. STUDY DESIGN: Patients (n = 8 males) were given escalating oral doses of delavirdine mesylate, in a sequential fashion, over 14 days for phases 1 (200 mg every 8 hours), 2 (300 mg every 8 hours), and 3 (400 mg every 8 hours). Control patients (n = 4 males) were given 300 mg oral doses of drug every 8 hours for all three phases. Hepatic CYP3A activity was evaluated with the erythromycin breath test (ERMBT). RESULTS: In the escalating-dose group, delavirdine displayed nonlinear kinetics as indicated by the decreasing oral clearance, maximum steady-state plasma concentration/minimum steady-state plasma concentration ratio, and log-linear terminal rate constant, as well as by increasing half-life at higher doses; the ratio of desisopropyl-delavirdine formation clearance to elimination clearance was also reduced. In the control group, the kinetics of delavirdine and desisopropyl-delavirdine were unchanged. Plasma protein binding was linear for delavirdine in the escalating-dose and control groups; on average, the fraction unbound was about 2.3% and 2.0%, respectively. Hepatic CYP3A activity was markedly reduced after short- and long-term exposure to all doses of delavirdine mesylate. Delavirdine could maximally inhibit 70% to 75% of predose ERMBT values, with an IC50 of about 0.9 mumol/L. CONCLUSION: Delavirdine is a potent and reversible inhibitor of hepatic CYP3A; it is also a substrate for this CYP450 isoform. It is likely that delavirdine will exhibit drug-drug interactions when coadministered with other CYP3A substrates.
Contamination between specimens within clinical microbiology laboratories may be responsible for spurious outbreaks of mycobacterial infections. We report the case of a patient who had culture-negative endocarditis and whose cardiac tissue obtained at surgery yielded Mycobacterium avium complex (MAC). Epidemiologic investigation suggested cross contamination probably occurred during processing of the sputum specimens of a patient with pulmonary MAC disease and the cardiac samples from our patient; molecular strain typing showed the isolates from both patients to be identical. When mycobacterial infection rates increase or an unexpected case of mycobacterial infection occurs, the clinician should be alert to the possibility of cross contamination in the laboratory as a possible explanation.
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Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.
Recent clinical data suggest that fluconazole at daily doses of 200 to 400 mg for at least 6 months is moderately effective therapy for non-life-threatening blastomycosis. To examine the usefulness of higher doses of fluconazole therapy for this disorder, we conducted a multicenter, randomized, open-label study to determine the efficacy and safety of two different daily doses of fluconazole (400 and 800 mg) in the treatment of non-life-threatening blastomycosis. Of 39 patients evaluable for efficacy analysis, 34 (87%) were successfully treated, including 89% and 85% of patients who received 400 and 800 mg, respectively. Five (83%) of six patients for whom prior antifungal therapy had failed were successfully treated. The mean duration of therapy was 8.9 months for successfully treated patients. Nineteen patients (48%) reported adverse events, although most were minor. We conclude that fluconazole at daily doses of 400 to 800 mg for at least 6 months is effective therapy for non-life-threatening blastomycosis.
OBJECTIVE: To compare the epidemiology of vancomycin-resistant Enterococcus faecium (VRE) in a long-term-care unit and an acute-care hospital. DESIGN: Point-prevalence surveys for VRE rectal colonization of patients were carried out over a 21-month period in patients in a long-term-care unit and an acute-care hospital (medical ward and intensive-care units). The environment and hands of healthcare workers also were sampled for VRE. Contour-clamped homogeneous electric field (CHEF) electrophoresis was used to evaluate possible transmission among roommates and the relatedness of patient strains to those in the environment and on the hands of healthcare workers. SETTING: A 200-bed Veterans Affairs Medical Center with an attached 90-bed long-term-care unit. RESULTS: From December 1994 to January 1996, rectal VRE colonization of patients in the long-term-care unit increased significantly from 9% to 22%. In contrast, patients on the medical ward rarely were colonized after the first survey in December 1994, and only two intensive-care-unit patients were found to be colonized during the four surveys. The environment was contaminated persistently in the long-term-care unit. In the four surveys, carriage of VRE on hands of healthcare workers varied from 13% to 41%; 65% of healthcare workers with VRE found on their hands worked in the long-term-care unit. Seven different strains were identified by CHEF typing. Although the initial survey found only vanA strains, subsequent surveys showed vanB strains also were present. CONCLUSIONS: Residents of a long-term-care unit frequently were colonized with VRE, but infections were uncommon in this population. The environment of the long-term-care unit was contaminated with VRE, and VRE was found frequently on the hands of healthcare workers in this unit. Both vanA and vanB genotypes were found in this setting.
We describe the first documented case of Mycoplasma felis infection in a woman who had common variable immunodeficiency and who presented with septic arthritis of the left hip and right knee. M. felis was isolated from both joints. She had been exposed to cats before the diagnosis of M. felis septic arthritis was made. Both of the patient's joints were surgically debrided, and she was treated with doxycycline for several months. In spite of initial improvement, destruction of her hip was noted. Subsequently, she underwent hip arthroplasty; histopathological examination of the bone at the time of surgery showed chronic osteomyelitis, and doxycycline therapy was continued.
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Significant advances in antifungal therapy have occurred in the last decade. Most of these advances have been tied to the introduction of the triazoles, itraconazole and fluconazole. Itraconazole has proved efficacious for the treatment of subacute to chronic infections with the endemic mycoses and other opportunistic filamentous fungi, including Aspergillus spp. Fluconazole is now routinely used for mucocutaneous and systemic candidiasis, and its use for coccidioidal meningitis has obviated the need for intrathecal amphotericin B in most patients. Large, well controlled trials in AIDS patients with cryptococcal meningitis have shown the benefit of induction therapy with amphotericin B and flucytosine, followed by consolidation and life-long maintenance therapy with fluconazole. Concomitant with the increased use of these well tolerated, effective oral triazole agents has come the emergence of drug resistance in AIDS patients and shifts in the species of yeasts causing infection in hospitalised patients. Amphotericin B remains the drug of choice for many fungal infections, especially those that are life-threatening. Lipid-containing formulations of amphotericin B have recently been approved: these preparations significantly reduce the risk of amphotericin B-induced nephrotoxicity. Several new fungicidal agents are currently in early trials. With the increasing number of available antifungal drugs, future studies will help define the appropriate niche for each and the possible benefit of therapy with combinations of drugs.
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Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.
Age alone is not usually sufficient for the development of disease due to Candida, but it appears to be associated with increased morbidity and mortality. Mucocutaneous Candida infections such as thrush and denture stomatitis are associated with local and mechanical factors. A rare and sight-threatening complication of cataract surgery is Candida endophthalmitis. Systemic Candida infections are becoming more common due to increasing use of immunosuppressive drugs and the increasing risk of nosocomial candidiasis in the intensive care unit. Candiduria is increasingly common in older patients with diabetes mellitus, indwelling urinary catheters, and a history of antibiotic therapy.
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