***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 
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    Input: Pulmonary fungal infection is diagnosed in up to 15 - 25 % of lung transplant recipients and frequently bears a fatal outcome . This prospect i ve uncontrolled study addresses the efficacy and safety of pre-emptive azole therapy against fungal infection in these patients . Fluconazole or itraconazole have been systematic ally used according to reported fungus sensitivity after the discovery of fungi in lower respiratory tract sample s. Patients were treated until the bronchial suture was normal and the cultures of the following bronchoscopy remained negative . Fungi were found post-transplantation in the lower respiratory tract specimens of 26 out of 31 ( 84 % ) patients , predominantly C and ida albicans ( 20 patients ) and Aspergillus fumigatus ( 16 patients ) . Mycelia characteristic of C and ida spp . or Aspergillus spp . were found in necrotic tissue at the bronchial suture of nine patients . The mean duration of the 38 treatments was 3.6+/-2.6 months ( range , 0.5 - 12 months ) . After a median follow-up of 16 ( range , 0 - 48 ) months , two cases of extended ulcerative and pseudo membranous Aspergillus fumigatus bronchitis were observed and healed under itraconazole treatment . In conclusion , pre-emptive azole therapy  may be effective and well-tolerated in lung transplant patients where fungi are found in the airways or pleura BACKGROUND Invasive fungal infections ( IFIs ) are a major cause of morbidity and mortality among organ transplant recipients . Multicenter prospect i ve surveillance data to determine disease burden and secular trends are lacking . METHODS The Transplant-Associated Infection Surveillance Network ( TRANSNET ) is a consortium of 23 US transplant centers , including 15 that contributed to the organ transplant recipient data set . We prospect ively identified IFIs among organ transplant recipients from March , 2001 through March , 2006 at these sites . To explore trends , we calculated the 12-month cumulative incidence among 9 sequential cohorts . RESULTS During the surveillance period , 1208 IFIs were identified among 1063 organ transplant recipients . The most common IFIs were invasive c and idiasis ( 53 % ) , invasive aspergillosis ( 19 % ) , cryptococcosis ( 8 % ) , non-Aspergillus molds ( 8 % ) , endemic fungi ( 5 % ) , and zygomycosis ( 2 % ) . Median time to onset of c and idiasis , aspergillosis , and cryptococcosis was 103 , 184 , and 575 days , respectively . Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006 , a total of 729 IFIs were reported among 633 persons . One-year cumulative incidences of the first IFI were 11.6 % , 8.6 % , 4.7 % , 4.0 % , 3.4 % , and 1.3 % for small bowel , lung , liver , heart , pancreas , and kidney transplant recipients , respectively . One-year incidence was highest for invasive c and idiasis ( 1.95 % ) and aspergillosis ( 0.65 % ) . Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005 . CONCLUSIONS We detected a slight increase in IFIs during the surveillance period . These data provide important insights into the timing and incidence of IFIs among organ transplant recipients , which can help to focus effective prevention and treatment strategies ABSTRACT Voriconazole prophylaxis is common following lung transplantation , but the value of therapeutic drug monitoring is unknown . A prospect i ve , observational study of lung transplant recipients ( n = 93 ) receiving voriconazole prophylaxis was performed .  Serum voriconazole troughs ( n = 331 ) were measured by high-pressure liquid chromatography . The median initial and subsequent troughs were 1.91 and 1.46 μg/ml , respectively . The age of the patient directly correlated with initial troughs ( P = 0.005 ) . Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs , respectively . In 95 % ( 88/93 ) of patients , ≥2 troughs were measured . In 28 % ( 25/88 ) and 32 % ( 28/88 ) of these patients , all troughs were ≤1.5 μg/ml or > 1.5 μg/ml , respectively . Ten percent ( 10/93 ) and 27 % ( 25/93 ) of the patients developed invasive fungal infection ( tracheobronchitis ) and fungal colonization , respectively . The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml ( P = 0.07 ) . Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml ( P = 0.01 ) and among patients with no trough of > 1.5 μg/ml ( P = 0.007 ) . Other cutoff troughs correlated less strongly with microbiologic outcomes . Troughs correlated directly with aspartate transferase levels ( P = 0.003 ) , but not with other liver enzymes  . Voriconazole was discontinued due to suspected toxicity in 27 % ( 25/93 ) of the patients . The troughs did not differ at the times of suspected drug-induced hepatotoxicity , central nervous system ( CNS ) toxicity , or nausea/vomiting and in the absence of toxicity  . Voriconazole prophylaxis was most effective at troughs of > 1.5 μg/ml . A cutoff for toxicity was not identified , but troughs of > 4 μg/ml were rare . The data support a target range of > 1.5 to 4 μg/ml Lung transplant recipients have one of the highest rates of invasive aspergillosis ( IA ) in solid organ transplantation . We used a single center , nonr and omized , retrospective , sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole ( n = 65 ) or targeted prophylaxis ( n = 30 ) with itraconazole ± inhaled amphotericin in patients at high risk ( pre‐ or posttransplant Aspergillus colonization [ except Aspergillus niger ] ) .  The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis ( 1.5 % vs. 23 % ; p = 0.001 ) . Twenty‐nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole . A threefold or higher increase in liver enzymes was noted in 37–60 % of patients receiving voriconazole prophylaxis as compared to 15–41 % of patients in the targeted prophylaxis cohort . Fourteen percent in the voriconazole group as compared to 8 % in the targeted prophylaxis group had to discontinue antifungal medications due to side effects . Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients . Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity BACKGROUND Fungal infections are an important complication of lung transplantation , but no controlled studies of their management have been performed . Knowledge of actual anti-fungal strategies may aid in the design of future prospect i ve studies . METHODS Thirty-seven of 69 active lung transplant centers , accounting for 66 % of all US lung transplantations , responded to our survey . The survey focused on fungal surveillance , pre- and post-transplant prophylaxis , and approach to fungal colonization . RESULTS The median number of lung transplantations performed by the centers in 1999 was 14 per year ( range , 1 - 52 ) , and median time that centers were in in operation was 9 years ( range , 2 - 15 years ) . Seventy percent of centers had a transplant infectious diseases specialist .  Pre-transplant fungal surveillance was performed by 81 % of centers , with 67 % of these surveying all patients and the remainder surveying only sub-sets of patients . Seventy-two percent of all centers started anti-fungal treatment if Aspergillus spp were isolated before transplantation . Itraconazole was the preferred agent ( 86 % ) . After transplantation , 76 % of centers gave anti-fungal prophylaxis , although 24 % of these did so only in selected patients . Prophylactic agents in order of preference were inhaled amphotericin B ( 61 % ) , itraconazole ( 46 % ) , parenteral amphotericin formulations ( 25 % ) , and fluconazole ( 21 % ) ; many centers used more than 1 agent . Prophylaxis was initiated within 24 hours by 71 % and within 1 week by all centers . Median duration of prophylaxis was 3 months ( range , < 1 month-lifetime ) . All 37 centers used  anti-fungal therapy if colonization with Aspergillus spp was detected for a median duration of 4.5 months . Itraconazole was the preferred agent . Only 59 % of centers treated patients colonized with C and ida spp . In a statistical analysis , centers with larger volumes were less likely to treat pre-transplant colonization with C and ida spp but more likely to use agents other than itraconazole for post-transplant colonization with Aspergillus spp . Only 14 % of centers engaged in any anti-fungal research at the time of the survey . CONCLUSIONS The majority of surveyed lung transplant programs actively manage fungal infection with prophylaxis or pre-emptive therapy , despite the absence of controlled trials . This survey may provide an impetus and a basis for design ing prospect i ve studies We conducted a survey of 50 lung transplant centers across the world to evaluate the variation in antifungal prophylaxis practice s. These 50 centers performed 63 % of the world 's lung transplants reported in 2001 . Eighty-six percent ( 43/50 ) of the centers responded to the survey . Sixty-nine percent ( 30/43 ) of centers used universal antifungal prophylaxis .  Aerosolized amphotericin B deoxycholate ( AmBd ) alone or in combination with itraconazole was used at 56 % ( 24/43 ) of centers . The median duration of prophylaxis with aerosolized AmBd and itraconazole was 30 and 90 days , respectively . Seventy-four percent of the centers surveyed agreed to participate in future research prophylaxis protocol s , which they felt should include both diagnostic and therapeutic arms . Our survey is the first documentation of the international variation in antifungal prophylactic strategies in lung transplant recipients , and underscores the need for multicenter , r and omized trials of antifungal prophylaxis in lung transplant recipients BACKGROUND Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation . The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis . METHODS The study group included 40 lung transplant recipients followed for at least 12 months . All received prophylactic itraconazole , 200 mg twice a day , for the first 6 months after transplantation .  Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy . Rejection rate , fungal infection rate , and renal function were assessed . The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated . RESULTS The mean tacrolimus dose during itraconazole treatment was 3.26 + /- 2.1 mg/day compared with 5.74 + /- 2.9 mg/day after itraconazole was stopped ( p < 0.0001 ) for a mean total daily dose elevation of tacrolimus of 76 % . When the cost of itraconazole was taken into account , the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone . No differences in the rejection or fungal infection rate , or in renal toxicity , were observed between the periods with and without itraconazole treatment , although less positive fungal isolates were identified during itraconazole therapy . CONCLUSION Prophylaxis therapy with itraconazole is highly effective . Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation Since July 1993 , amphotericin B ( 5 mg TID to be increased up to 20 mg TID within 5 days after surgery ) has been given as inhalation throughout the posttransplant hospital stay . This group consists of 12 
    Output:
    
We did not find a significant reduction in IA or Aspergillus colonization with universal anti-aspergillus prophylaxis .
There was no difference in the adverse events of inhaled amphotericin-B deoxycholate and lipid formulations of inhaled amphotericin-B.  However , voriconazole was more hepatotoxic than itraconazole .