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 822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical findings, pathologic features, and outcome were investigated in 46 patients in whom Torulopsis glabrata was isolated in 131 specimens of blood. Nineteen of the patients had only a single positive blood culture and no evidence of systemic yeast infection, while 27 patients had a clinically significant fungemia based upon the occurrence of 2 or more positive blood cultures, or the combination of a positive blood culture and isolation of the organism from a closed body cavity or demonstration of the yeast in tissue sections. The predisposing factors to the development of fungemia included the presence of intravenous lines, indwelling Foley catheters, antibiotics and surgery, especially when the gastrointestinal tract was involved. Only 22% of patients received either steroids or cytostatic agents. Possible portals of entry were suggested by the prior isolation of the organism from urine, sputum, wounds, and central venous catheter tips in most of the patients. Twelve of 27 patients with clinically significant fungemia were treated. The initial mode of therapy in nine patients was removal of intravenous lines because of the clinical suspicion of catheter related sepsis. Seven of the patients improved rapidly and one more after amphotericin B was subsequently administered. Amphotericin B was the initial therapy in three cases. One patient was cured while another died of an unrelated infection. Five patients were not treated although the isolation of T. glabrata had been reported; the fact that the presence of the organism was felt to be unimportant was considered to be a factor in the delay of treatment. In the remaining 10 patients the organism was isolated only after the patient had died. Division of the patients into four groups based upon whether the individuals survived, died of unrelated disease, died with potentially lethal infection, or died with T. glabrata infection significantly contributing to death, revealed a spectrum of disease, certain signs of which appeared to be of predictive value as prognostic indices of survival and severity of the infection. Seven patients with transient fungemia experienced an acute episode of high spiking fever (greater than 102.5 degrees F), rigors and/or hypotension, six of whom improved after the intravenous catheter was removed, suggesting a catheter-related sepsis. In contrast, persistent low grade fever (less than 102.5 degrees F) characterized eight of the nine patients in whom T. glabrata infection was considered either potentially lethal, or contributing significantly to death. A deteriorating clinical course with organ failure was also associated with this latter category of patients. Catheter-induced specticemia was considered in only two patients in this category. The autopsy and clinical findings in this investigation as well as reported experimental studies suggest that T. glabrata is an organism of low virulence. The patients' underlying disease (e.g., neoplasia) and coexisting bacterial infection are the most important factors responsible for death.
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PMID:Torulopsis glabrata fungemia--a clinical pathological study. 57 9

In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p = 0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p = 0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p = 0.04) and significantly fewer patients had a decrease of more than 25% in creatinine clearance on the sixth day (4/12 vs 9/11 p = 0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects.
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PMID:Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B. 142 31

A retrospective analysis was carried out of the results of 115 intensively-treated cancer inpatients receiving 91 treatment courses of amphotericin B given in an empirical fashion. Amphotericin B was administered over 1.5 to 2 hours at a dose of 0.6 to 0.7 mg/kg/day. Median duration of neutropenic fever before amphotericin B administration was 5 days (range 1 to 32 days) and median total amphotericin B dose was 480 mg (range 10 to 2450 mg). In 56 (61%) of 91 amphotericin B courses, neutropenic fevers resolved; this occurred a median of 3 days (range 1 to 15 days) after amphotericin B was begun and at a median dose of 120 mg (range 10 to 850 mg). Response to amphotericin was independent of positive cultures for fungus or sites of positive culture. Adverse reactions to amphotericin B included rigors (89% of courses), fever (23%), bronchospasm (9%), and transient hypotension (9%). Median increase above baseline serum creatinine in patients given amphotericin B was 0.5 mg/dl (range 0 to 2.6 mg/dl) compared to a median of 0.1 mg/dl (range 0 to 2.9 mg/dl) in a similar group of intensively-treated cancer patients who did not receive amphotericin B. Amphotericin B was well tolerated when given by rapid infusion and was associated with prompt resolution of neutropenic fever in the majority of patients.
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PMID:Rapid infusion amphotericin B: effective and well-tolerated therapy for neutropenic fever. 274 90

Amphotericin B incorporated into small unilamellar liposomes prepared from soya phosphatidylcholine and cholesterol in a molar ratio of 7:3 was administered to 12 patients with suspected or documented systemic fungal infection. Each patient received 0.1, 0.4 and 1.0 mg/kg dose of liposomal amphotericin B. Liposomal amphotericin B was well tolerated by these patients with no dose-limiting toxicity. Mild to moderate fever with rigors occurred in 3 patients after the higher doses. Peak plasma amphotericin B concentrations, measured by HPLC; were 0.747-1.429 mg/L and 24 h trough concentrations were 0.148-0.363 mg/L. The mean T1/2 beta of amphotericin B was 17.2 h with a mean volume of distribution of 2.285 L/kg. While these pharmacokinetic parameters obtained with this liposomal amphotericin B formulation are comparable to the values obtained after conventional amphotericin B therapy, they are strikingly different from values obtained by other workers using small unilamellar liposomes with either positive or negative charge. Yet in animal experiments the distribution of all formulations are comparable.
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PMID:Pharmacokinetics and tolerance of liposomal amphotericin B in patients. 822 4

Amphotericin B colloidal dispersion (ABCD; Amphocil) was evaluated in a phase I dose-escalation study in 75 marrow transplant patients with invasive fungal infections (primarily Aspergillus or Candida species) to determine the toxicity profile, maximum tolerated dose, and clinical response. Escalating doses of 0.5-8.0 mg/kg in 0.5-mg/kg/patient increments were given up to 6 weeks. No infusion-related toxicities were observed in 32% of the patients; 52% had grade 2 and 5% had grade 3 toxicity. No appreciable renal toxicity was observed at any dose level. The estimated maximum tolerated dose was 7.5 mg/kg, defined by rigors and chills and hypotension in 3 of 5 patients at 8.0 mg/kg. The complete or partial response rate across dose levels and infection types was 52%. For specific types of infections, 53% of patients with fungemia had complete responses, and 52% of patients with pneumonia had complete or partial responses. ABCD was safe at doses to 7.5 mg/kg and had tolerable-infusion-related toxicity and demonstrable antifungal activity.
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PMID:Phase I study of amphotericin B colloidal dispersion for the treatment of invasive fungal infections after marrow transplant. 862 74

Hematogenously disseminated candidiasis arising from nosocomial fungal infection is a life-threatening complication in critically ill, nonneutropenic patients. The overall nosocomial fungal infection rate in United States hospitals doubled from 1980-1990. Until recently, amphotericin B was the only agent available for the treatment of life-threatening candidal infections, but its use is plagued by toxicities including nephrotoxicity and infusion-related reactions such as rigors and hypotension. The availability of fluconazole, which is regarded as much less toxic than amphotericin B, prompted a surge in research to determine if it is as efficacious in the management of candidemia and hematogenously disseminated candidiasis. Complicating the interpretation of studies is the broad range of infection severity, from candidemia that may be transient and self-limiting to life-threatening hematogenously disseminated candidiasis. Clinical trials comparing fluconazole and amphotericin B demonstrate the efficacy of fluconazole for catheter-associated candidemia in critically ill patients when the likely pathogen is Candida albicans. Amphotericin B should remain the first-line agent for the management of candidemia and hematogenously disseminated candidiasis in all other patients.
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PMID:The fluconazole era: management of hematogenously disseminated candidiasis in the nonneutropenic patient. 916 56

Amphotericin B colloidal dispersion (ABCD) is a novel lipid formulation of amphotericin B designed to diminish toxic effects of the drug. In the following report, nine cases of suspected (n = 4) and proven (n = 5) deep Candida infection, treated sequentially with amphotericin B deoxycholate and ABCD, are presented. The treatment was successful in seven cases. During treatment with amphotericin B deoxycholate, a rise in serum creatinine was observed in seven patients, hypokalemia in five, and metabolic acidosis in four. After replacing amphotericin B deoxycholate with ABCD, laboratory parameters improved in four of the seven patients with increased creatinine, in four of the five patients with hypokalemia, and in two of the four patients with metabolic acidosis. Infusion-related rigors were observed in four patients receiving amphotericin B deoxycholate and in one patient treated with ABCD. Reversible elevation of liver enzymes was found in one patient receiving ABCD. In this study ABCD proved less toxic than amphotericin B deoxycholate. The efficacy of ABCD alone cannot be assessed because of previous treatment with amphotericin B deoxycholate, but sequential treatment of deep Candida infections with amphotericin B deoxycholate and ABCD seems to be an effective therapeutic modality, especially in patients requiring prolonged administration of amphotericin B.
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PMID:Sequential treatment of deep fungal infections with amphotericin B deoxycholate and amphotericin B colloidal dispersion. 927 85

A considerable effort has been spent in the past three decades to investigate various aspects of liposomes as novel drug delivery systems. In 1990, the first amphotericin B (AmB) liposomal preparation (L-AmB) under the brand name AmBisome was introduced into the market by Vestar. The successful marketing of the product moved liposomes out of the stage of experimental obscurity to the realistic stage of clinical utility. The launch of AmBisome sparked off the introduction of other lipid-based AmB products marketed by Liposome Technology (Amphocil) and The Liposome Co. (Abelcet). The drive behind the development of a modified formulation of AmB was to improve the therapeutic index of this drug with respect to its major drawback associated with both acute and chronic toxic effects. In a 30-year-long experience with AmB, several reports were recorded in the literature of acute adverse effects, such as fever, rigors, vomiting, cardiotoxicity and hypotension occurring during infusion; while long-term therapy was reported to be associated with hypokalemia, renal dysfunction and hematological abnormalities. Another serious problem encountered with the drug had been the poor response obtained in immunocompromised patients like those with AIDS, neutropenia and cancer patients on chemotherapy. The encapsulation of amphotericin B in liposomal vesicles was hence targeted not only to obtain an improvement in the therapeutic index but also to see if it was useful in eradicating deep-seated fungal infections in immunocompromised patients. The liposomal AmB was found to have a better therapeutic index and lower toxicity than the commercial AmB preparations. The LD50 of AmBisome in mouse was 175 mg/kg compared with 3.7 mg/kg for Fungizone, the commercial preparation of AmB. Additionally, L-AmB has prolonged circulation time, and extravasates into the site of infection and delivers the drug directly to the site, with no nephrotoxicity and neurotoxicity as experienced with AmB. This review traces the course of development of L-AmB and discusses the rationale behind the development of its liposomal preparation. The results in in vitro, in vivo and clinical studies, mechanism of action, biodistribution, and formulation considerations of L-AmB are described. The clinical experience with the marketed preparation is reviewed.
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PMID:Development of liposomal amphotericin B formulation. 953 20

A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in a fat emulsion (Intralipid) in cancer patients. Group 1 (n = 33) received amphotericin B diluted in 5% dextrose with premedication consisting of promethazine plus an antipyretic. Group 2 (n = 28) received amphotericin B diluted in 20% Intralipid without premedication. Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy (in neutropenic patients) or for the treatment of documented fungal infections. The majority of patients (80%) received empirical amphotericin B treatment. The two groups were comparable with regard to age, gender, underlying disease, and the following baseline characteristics: use of other nephrotoxic drugs and serum levels of potassium and creatinine. The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 (P = 0.73). Acute adverse events occurred in 88% of patients in group 1 and in 71% of those in group 2 (P = 0.11). Forty percent of the infusions in group 1 were associated with fever, compared to 23% in group 2 (P < 0.0001). In addition, patients in group 2 required less meperidine for the control of acute adverse events (P = 0.008), and fewer members of this group presented with hypokalemia (P = 0.004) or rigors (P < 0.0001). There was no difference in the proportions of patients with nephrotoxicity (P = 0.44). The success rates of empirical antifungal treatment were similar in the two groups (P = 0.9). Amphotericin B diluted in a lipid emulsion seems to be associated with a smaller number of acute adverse events and fewer cases of hypokalemia than amphotericin B diluted in 5% dextrose.
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PMID:Comparison of the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in fat emulsion in a randomized trial with cancer patients. 1034 68

Amphotericin B is commonly used in the intensive care unit to treat invasive fungal infection. This medication is associated with a number of adverse events during infusion, such as fever, rigors, chills, electrolyte disorders and renal insufficiency. Liposomal amphotericin B can be used as an alternative to conventional amphotericin B to treat fungal infection. Patients receiving liposomal amphotericin B experience fewer adverse events than recipients of the conventional formulation; moreover, the liposomal formulation has been found to be as effective as the conventional amphotericin B to treat specific fungal infections. Unfortunately, the pharmacoeconomics of the liposomal formulation has limited the use of this medication. The purpose of this article is to present a brief summary of conventional amphotericin B with an emphasis on the narrow therapeutic index of this antibiotic. The liposomal amphotericin B solution is compared to conventional amphotericin B regarding the pharmacokinetics and pharmacodynamics. Therapeutic use, tolerability, and pharmacoeconomic implications of liposomal amphotericin B are discussed.
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PMID:Liposomal amphotericin B for the treatment of severe fungal infection. 1198 30


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