***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE In a r and omized , double-blind , comparative , multicenter trial , liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients , using a composite end point , but was more effective in reducing proven emergent fungal infections , infusion-related toxicities , and nephrotoxicity . The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy . PATIENTS AND METHODS Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial .  Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed . RESULTS Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ( $ 48,962 v $ 43,183 ; P = .022 ) . However , hospital costs were highly sensitive to the cost of study medication ( $ 39,648 v $ 43,048 when drug costs were not included ; P = .416 ) . Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity , the break-even points for the cost of liposomal therapy  were calculated to range from $ 72 to $ 87 per 50 mg for all patients and $ 83 to $ 112 per 50 mg in allogeneic bone marrow transplant patients . CONCLUSION The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients Abstract Objective : To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion . Design : R and omised , controlled , non-blinded , single centre study . Setting : University hospital providing tertiary clinical care . Patients : 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections . Intervention : Patients were r and omised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours . Main outcome measures : Patients were evaluated for side effects related to infusion , nephrotoxicity , and mortality up to three months after treatment . Analysis was on an intention to treat basis . Results : Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group . Overall mortality was higher during treatment and after three months ' follow up in the rapid infusion than in the continuous infusion group . Conclusion : Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing ABSTRACT A multicentric r and omized 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 ABSTRACT In a prospect i ve , r and omized clinical trial , the toxicity of 1 mg of amphotericin B ( AmB ) per kg of body weight per day infused in 5 % dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease . In an analysis of 82 children who received a full course of 6 days or more of AmB ( 117 courses ) , it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion , with there being no difference between the two methods of AmB administration . An intent-to-treat comparison of the numbers of courses affected by acute toxicity ( fever , rigors ) and chronic toxicity ( nephrotoxicity ) also indicated that there was no significant difference between AmB infused in dextrose ( 78 courses ) and AmB infused in lipid emulsion ( 84 courses ) . The pharmacokinetics of AmB  were investigated in 20 children who received AmB in dextrose and 15 children who received AmB in lipid emulsion .  Blood sample s were collected up to 24 h after administration of the first dose , and the concentration of AmB in plasma was analyzed by a high-performance liquid chromatography assay . The clearance ( CL ) of AmB in dextrose ( 0.039 ± 0.016 liter · h−1 · kg−1 ) was significantly lower ( P < 0.005 ) than the CL of AmB in lipid emulsion ( 0.062 ± 0.024 liter · h−1 · kg−1 ) . The steady-state volume of distribution for AmB in dextrose ( 0.83 ± 0.33 liter · kg−1 ) was also significantly lower ( P < 0.005 ) than that for AmB in lipid emulsion ( 1.47 ± 0.77 liter · kg−1 ) . Although AmB in lipid emulsion is apparently cleared faster and distributes more widely than AmB in dextrose , this study did not reveal any significant advantage with respect to safety and tolerance in the administration of AmB in lipid emulsion compared to its administration in dextrose in children with malignant disease We report a r and omized , double-blind , multicenter trial in which amphotericin B colloidal dispersion ( ABCD [ Amphotec ] ; 6 mg/kg/day ) was compared with amphotericin B ( AmB ; 1.0 - 1.5 mg/kg/day ) for the treatment of invasive aspergillosis in 174 patients . For evaluable patients in the ABCD and AmB treatment groups , respective rates of therapeutic response ( 52 % vs. 51 % ; P=1.0 ) , mortality ( 36 % vs. 45 % ; P=.4 ) , and death due to fungal infection ( 32 % vs. 26 % ; P=.7 ) were similar . Renal toxicity was lower ( 25 % vs. 49 % ; P=.002 ) and the median time to onset of nephrotoxicity was longer ( 301 vs. 22 days ; P<.001 ) in patients treated with ABCD . Rates of drug-related toxicity in patients receiving ABCD and AmB , respectively , were 53 % versus 30 % ( chills ) , 27 % versus 16 % ( fever ) , 1 % versus 4 % ( hypoxia ) and 22 % versus 24 % ( toxicity requiring study drug discontinuation ) . ABCD appears to have equivalent efficacy and superior renal safety , compared with AmB , in the treatment of invasive aspergillosis . However , infusion-related chills and fever occurred more frequently in patients receiving ABCD than in those receiving Abstract Objective : To compare the feasibility of treatment , safety , and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid for empirical antimycotic treatment of neutropenic cancer patients . Design : Single centre stratified , r and omised non-blinded phase II study . Setting : University hospital providing tertiary clinical care . Subjects : 51 neutropenic patients ( leukaemia ( 35 ) , lymphoma ( 11 ) , solid tumours ( 5 ) ) with refractory fever of unknown origin ( 24 ) or pneumonia ( 27 ) . Interventions : Amphotericin B 0.75 mg/kg/day in 250 ml glucose 5 % solution or mixed with 250 ml intralipid 20 % , given on eight consecutive days then alternate days , as a 1 - 4 hour infusion . Main outcome measures : Feasibility of treatment , subjective tolerance ( question naire ) , and objective toxicity ( common toxicity criteria of the National Cancer Institute ) . Results : Study arms were balanced for age , sex , underlying malignancy , renal and liver function , and pre- and concomitant treatment with antibiotics and nephrotoxic agents . No statistically significant or clinical ly relevant differences were found between the treatment groups for : daily or cumulative dose and duration of treatment with  amphotericin B ; incidence and time of dose modifications or infusion duration changes related to toxicity ; dose or duration of symptomatic support with opiates , antipyretics , or antihistamines ; renal function ; subjective tolerance ; most common toxicity scores ; course of infection ; and incidence of treatment failures . Patients treated with amphotericin B in intralipid were given fewer diuretics ( P<0.05 ) and therefore had more peripheral oedema ( P<0.01 ) and needed less potassium supplementation ( P<0.05 ) than patients given amphotericin in glucose . Acute respiratory events were more common in the intralipid arm ( P<0.05 ) . Conclusions : Amphotericin B 0.75 mg/kg/day in intralipid given on eight consecutive days then alternate days provides no benefit and is associated with potential pulmonary side effects possibly because of fat overload or an incompatibility of the two drugs We conducted a prospect i ve , r and omized , double-blind study comparing amphotericin B colloidal dispersion ( ABCD ) with amphotericin B in the empirical treatment of fever and neutropenia . Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus . Patients were then r and omized to receive therapy with ABCD ( 4 mg/[kg.d ] ) or amphotericin B ( 0.8 mg/[kg.d ] ) for < or = 14 days . A total of 213 patients were enrolled , of whom 196 were evaluable for efficacy .  Fifty percent of ABCD-treated patients and 43.2 % of amphotericin B-treated patients had a therapeutic response ( P = .31 ) . Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients ( P < .001 for both parameters ) . Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients ( P = .013 and P = .018 , respectively ) . ABCD appeared comparable in efficacy with amphotericin B , and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However , infusion-related events were more common with ABCD treatment than with amphotericin B treatment The clinical use of amphotericin B is sometimes limited by nephrotoxicity . In a r and omized prospect i ve study , 32 patients treated for haematological malignancies received either amphotericin B in 5 % dextrose ( group A , 16 patients , 0.7 - 1 mg/kg/day ) , or amphotericin B mixed with Intralipid ( group B , 16 patients , 0.7 - 1 mg/kg/day ) during prolonged neutropenia . Renal dysfunction occurred in 9/16 patients in group A and 2/16 patients in group B ( P < 0.05 ) . Clinical tolerance was improved with a reduction of fever with chills in 12/16 patients in group A compared with 5/16 in group B ( P < 0.05 ) . Preparation of amphotericin B with Intralipid reduces nephrotoxicity , 
    Output:
    
Lipid-based amphotericin B was not more effective than conventional amphotericin B on mortality ( relative risk ( RR ) 0.5 ; 95 % confidence interval ( CI ) 0.64 to 1.14 ) but decreased invasive fungal infection ( RR 0.65 ; 95 % CI 0.44 to 0.97 ) , nephrotoxicity defined as a 100 % increase in serum creatinine ( RR 0.45 ; 95 % CI 0.37 to 0.54 ) , and number of dropouts ( RR 0.78 ; 95 % CI 0.62 to 0.97).For the drug used in most patients , AmBisome ( 4 trials , 1214 patients ) , there was no significant difference in mortality ( RR 0.77 ; 95 % CI 0.54 to 1.10 ) whereas it tended to be more effective than conventional amphotericin B on invasive fungal infection ( RR 0.63 ; 95 % CI 0.39 to 1.01 , P value 0.053).AmBisome , amphotericin B in Intralipid ( 6 trials , 379 patients ) , amphotericin B colloidal dispersion ( ABCD ) ( 2 trials , 262 patients ) , and amphotericin B lipid complex ( ABLC ) ( 1 trial , 105 patients ) all decreased the occurrence of nephrotoxicity , but conventional amphotericin B was rarely administered under optimal circumstances .