***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 To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer . PATIENTS AND METHODS A total of 317 neutropenic patients ( < 500 cells/mm3 ) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were r and omly assigned to receive either fluconazole ( 400 mg intravenously once daily ) or amphotericin B ( 0.5 mg/kg once daily ) . Patients were evaluated for the efficacy and safety of each drug by clinical criteria , frequent cultures and radiological procedures , and laboratory values . A response was classified as satisfactory at the end of therapy if the patient was afebrile , had no clinical or microbiological evidence of fungal infection , and did not require study termination due to lack of efficacy , drug toxicity , or death . RESULTS A satisfactory response occurred in 68 % of the patients treated with fluconazole ( 107 of 158 patients ) and in 67 % of patients treated with amphotericin B ( 106 of 159 patients ) . Progressive or new fungal infections during therapy occurred in 13 ( 8 % ) patients treated with fluconazole ( 8 with C and ida , 5 with Aspergillus ) and in 10 ( 6 % ) patients treated with amphotericin B ( 5 with C and ida , 3 with Aspergillus , 2 with other fungi ) . Adverse events related to study drug ( especially fever , chills , renal insufficiency , electrolyte disturbances , and respiratory distress ) occurred more often in patients treated with amphotericin B ( 128 [ 81 % ] of 159 patients ) than patients treated with fluconazole ( 20 [ 13 % ] of 158 patients , P = 0.001 ) . Eleven ( 7 % ) patients treated with amphotericin B but only 1 ( 1 % ) patient treated with fluconazole were terminated from the study owing to an adverse event ( P = 0.005 ) . Overall mortality ( 27 [ 17 % ] patients treated with fluconazole versus 34 [ 21 % ] patients treated with amphotericin B ) and mortality from fungal infection ( 7 [ 4 % ] patients treated with fluconazole versus 5 [ 3 % ] patients treated with amphotericin B ) were similar in each study group . CONCLUSIONS Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients . However , because fluconazole may be ineffective in the treatment of Aspergillus , patients at risk for that infection should be evaluated by chest radiograph , computed tomographic scanning , and cultures before the use of empiric fluconazole therapy BACKGROUND Voriconazole is a broad-spectrum triazole that is active against aspergillus species . We conducted a r and omized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis . METHODS In this r and omized , unblinded trial , patients received either intravenous voriconazole ( two doses of 6 mg per kilogram of body weight on day 1 , then 4 mg per kilogram twice daily for at least seven days ) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate ( 1 to 1.5 mg per kilogram per day ) . Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used . A complete or partial response was considered to be a successful outcome . RESULTS A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment . In most of the patients , the underlying condition was allogeneic hematopoietic-cell transplantation , acute leukemia , or other hematologic diseases . At week 12 , there were successful outcomes in 52.8 percent of the patients in the voriconazole group ( complete responses in 20.8 percent and partial responses in 31.9 percent ) and 31.6 percent of those in the amphotericin B group ( complete responses in 16.5 percent and partial responses in 15.0 percent ; absolute difference , 21.2 percentage points ; 95 percent confidence interval , 10.4 to 32.9 ) . The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group ( hazard ratio , 0.59 ; 95 percent confidence interval , 0.40 to 0.88 ) . Voriconazole-treated patients had significantly fewer severe drug-related adverse events , but transient visual disturbances were common with voriconazole ( occurring in 44.8 percent of patients ) . CONCLUSIONS In patients with invasive aspergillosis , initial therapy with voriconazole led to better responses and improved survival and result ed in fewer severe side effects than the st and ard approach of initial therapy with amphotericin BACKGROUND Aspergillosis therapy with amphotericin , azoles , or echinoc and ins is associated with substantial mortality , ranging from 30 % to 80 % , depending on the stage of infection and the host 's underlying disease . The results of in vitro studies and animal models suggest that combination therapy with azoles and echinoc and ins may have additive activity against Aspergillus species . METHODS We evaluated the outcomes of patients with aspergillosis who experienced failure of initial therapy with amphotericin B formulations and received either voriconazole ( n=31 ) or a combination of voriconazole and caspofungin ( n=16 ) for salvage therapy . RESULTS The combination of voriconazole and caspofungin was associated with improved 3-month survival rate , compared with voriconazole alone ( hazard ratio [ HR ] , 0.42 ; 95 % confidence interval [ CI ] , 0.17 - 1.1 ; P=.048 ) . In multivariable models , salvage therapy with the combination of voriconazole and caspofungin was associated with reduced mortality , compared with therapy with voriconazole ( HR , 0.28 ; 95 % CI , 0.28 - 0.92 ; P=.011 ) , independent of other prognostic variables ( e.g. , receipt of transplant and type of conditioning therapy ) . The probability of death due to aspergillosis was lowest in patients who received the combination regimen . CONCLUSIONS R and omized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis Background : Invasive c and idiasis is increasingly prevalent in premature infants and seriously ill children , and pediatric data on available antifungal therapies are lacking . Methods : We conducted a pediatric sub study as part of a double-blind , r and omized , multinational trial to compare micafungin ( 2 mg/kg ) with liposomal amphotericin B ( 3 mg/kg ) as first-line treatment of invasive c and idiasis .  Treatment success was defined as clinical and mycologic response at the end of therapy . Statistical analyses were descriptive , as the sample size meant that the study was not powered for hypothesis testing . Results : One hundred six patients were included in the intent-to-treat population ; and 98 patients —48 patients in the micafungin group and 50 patients in the liposomal amphotericin B group — in the modified intent-to-treat population . Baseline characteristics were balanced between treatment groups . Overall , 57 patients were < 2 years old including 19 patients who were premature at birth ; and 41 patients were 2 to < 16 years old . Most patients ( 91/98 , 92.9 % ) had c and idemia , and 7/98 ( 7.1 % ) patients had other forms of invasive c and idiasis . Treatment success was observed for 35/48 ( 72.9 % ) patients treated with micafungin and 38/50 ( 76.0 % ) patients treated with liposomal amphotericin B. The difference in proportions adjusted for neutropenic status was −2.4 % [ 95 % CI : ( −20.1 to 15.3 ) ] . Efficacy findings were consistent , independent of the neutropenic status , the age of the patient , and whether the patient was premature at birth . Both treatments were well tolerated , but with a lower incidence of adverse events that led to discontinuation in the micafungin group ( 2/52 , 3.8 % ) compared with the liposomal amphotericin B group ( 9/54 , 16.7 % ) ( P = 0.05 , Fisher exact test ) . Conclusions : Micafungin seems to be similarly effective and as safe as liposomal amphotericin B for the treatment of invasive c and idiasis in pediatric patients . ( Clinical Trials.gov number , NCT00106288 ) The epidemiology , management , and long-term survival of invasive aspergillosis was assessed in a prospect i ve , 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies . Invasive aspergillosis occurred exclusively in the context of haematological malignancies , where it accounted for an incidence of 6.8 % ( n = 13 of 189 ) . The lung was the primary site in 12 cases , and dissemination was present in three of those . Prior to diagnosis , the overwhelming majority of patients had been profoundly neutropenic for at least 14 days ( n = 11 of 13 ) and were receiving systemic antifungal agents  ( n = 10 of 13 ) . Clinical signs and symptoms were nonspecific but always included fever . All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment  , and seven were cured ( 64 % ) . Nevertheless , the overall long-term survival was merely 31 % after a median follow-up of 5.68 years after diagnosis . Apart from refractory or recurrent cancer , the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis . The frequency of invasive aspergillosis of greater than 15 % in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups Coccidioidomycosis is a systemic fungal infection caused by Coccidioides immitis . Typically , infection stimulates a protective immune response that limits the initial illness and confers lifelong resistance to subsequent infections ( 1 ) . Occasionally , however , illness progresses , either as a fibrocavitary chronic pneumonia or hematogenously , with dissemination of infection to such extrathoracic sites as the skin , bones , or joints ( 2 , 3 ) . If these complications occur , antifungal therapy is warranted to prevent further tissue destruction and associated morbidity ( 4 ) . Azole antifungal agents have become valuable in treating progressive forms of coccidioidomycosis , especially when disease manifestations are not fulminant or immediately life-threatening . Originally , the U.S. Food and Drug Administration approved intravenous miconazole and oral ketoconazole for this indication on the basis of their efficacy and safety ( 5 - 14 ) . The lack of an oral form of miconazole and untoward effects or drug intolerance related to both agents led to the development of fluconazole , itraconazole , and related congeners . These new drugs have shown therapeutic efficacy against coccidioidomycosis in experimental infections of animals ( 15 - 20 ) and in subsequent clinical trials ( 21 - 30 ) . Our current underst and ing of optimal management of coccidioidal infections is severely limited by the absence of r and omized comparative trials that evaluate the different forms of therapy . Multicenter comparative trials are now possible because over the past decade , the evaluation of patients treated for coccidioidomycosis has become st and ardized . In addition , because of the development of a collaborative group during the same period , trials can now enroll enough patients to support clinical ly applicable results . In this report , we present the findings from Mycoses Study Group Protocol 20 , a comparative trial sponsored by the National Institute of Allergy and Infectious Diseases that compares two antifungal agents , fluconazole and itraconazole , in the treatment of coccidioidomycosis . Methods Patient Eligibility Patients were considered for enrollment if C. immitis was identified by culture , by microscopic examination of infected tissue from outside the lungs , or from respiratory specimens , if a pulmonary infection had persisted for more than 3 months . Patients with HIV infection and pulmonary coccidioidomycosis of shorter duration were eligible if their CD4 count was less than or equal to 0.25 109 cells/L or if they had diffuse bilateral pneumonia . Enrollees had to be able to take oral medications . Pregnant women were excluded , and women of childbearing potential were required to practice an effective method of birth control 
    Output:
    
No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia .
Limited paediatric data are available comparing antifungal agents in children with proven , probable or suspected invasive fungal infection .
No differences in mortality or treatment efficacy were observed when antifungal agents were compared .