***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: OBJECTIVES Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures . Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients . MATERIAL S AND METHODS In this prospect i ve trial , 201 kidney transplant patients were r and omized ( 1:1 ) to receive 450 mg/d  ( group 1 , n = 100 ) or 900 mg/d  ( group 2 , n = 101 ) valganciclovir prophylaxis for the first 6 months after transplant . Patients were studied for incidence of cytomegalovirus disease , leucopenia episodes , rejection episodes , and graft outcomes along with associated costs over 1 year . Costs ( in US dollars ) of treatment of rejection were also analyzed . RESULTS Demographic features of the studied groups were comparable . We found that the cost of cytomegalovirus care in group 1 patients was significantly lower ( by 50 % at 6 months ; P < .001 ) , with less leukopenia episodes ( P = .04 ) , lower doses of granulocyte colony-stimulating factor ( by 30 % at 6 months ; P = .03 ) , higher doses of mycophenolate mofetil ( P = .04 ) , and less rejection episodes ( P = .01 ) compared with group 2 . In group 2 , there were more episodes of cytomegalovirus infection ( P = .052 ) and BK virus nephropathy ( P = .04 ) . Graft and patient outcomes were satisfactory in both groups . CONCLUSIONS Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer , effective and without breakthrough infection , and less costly than using the usual dose Background Few studies have directly compared preemptive therapy ( PET ) and antiviral prophylaxis ( AP ) for prevention of cytomegalovirus ( CMV ) disease in CMV seropositive ( R+ ) orthotopic liver transplant ( OLT ) recipients . Methods We prospect ively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET ( weekly plasma CMV PCR for 3 months ,  oral valganciclovir  900 mg twice daily for CMV viremia > 250 IU/mL , until 2 consecutive negative weekly PCR results ) and compared them with a historical cohort of 156 R+ recipients who received AP ( valganciclovir , 900 mg daily  for 3 months ) . Results Patient characteristics were similar between PET and AP cohorts ( P > 0.05 all comparisons ) . In the PET group , 24 % ( 39/160 ) developed CMV viremia greater than 250 IU/mL at a median of 42 ( range , 7 - 93 ) days post-OLT . CMV monitoring adherence in the PET cohort was 85 % ( 1488/1760 required tests ) and 86 % ( 30/36 ) initiated PET within 3 days of the CMV result . By 12 months post-OLT , the incidence of CMV disease , acute allograft rejection , major infection , or death in the PET and AP cohorts was not significantly different : 2 % versus 2 % , 19 % versus 16 % , 10.5 % versus 10.8 % , and 5 % versus 8 % , respectively ( P > 0.05 all comparisons ) . The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP : 24 % versus 100 % , P < 0.001 , and 15.8 versus 81 g per patient , P < 0.001 , respectively . Conclusions PET is feasible in a non research setting and is associated with similar CMV disease rates and other clinical ly relevant outcomes to AP in CMV seropositive liver transplant recipients OBJECTIVES Invasive fungal infections ( IFIs ) cause significant morbidity and mortality among recipients of hematopoietic stem cell transplantation ( HSCT ) . Although fluconazole is used widely as an antifungal prophylactic agent in these patients , it is not reliably effective against mold infection including invasive aspergillosis . Micafungin provides antifungal activity against C and ida and Aspergillus species , and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients . Here , we evaluated and compared the incidence of proven or probable IFIs after antifungal prophylaxis using micafungin or fluconazole . METHODS This was a prospect i ve , single-center , phase II study involving adult patients who received allogeneic or autologous HSCT . Patients were r and omly assigned to micafungin or fluconazole arms in a ratio of 2:1 , and the treatment was initiated within 24 h of HSCT and maintained for up to 21 days . The primary end point was the incidence of proven or probable IFIs during the 100 days after HSCT . The secondary end points were the incidence rates of possible , proven , or probable IFIs , need to change the antifungal agent before engraftment , IFI-related mortality , and survival within 100 days after transplantation . RESULTS Between March 2010 and May 2015 , a total of 257 patients were enrolled . After exclusion of seven patients who did not receive at least one dose of a study treatment , 250 patients ( micafungin , n = 165 ; fluconazole , n = 85 ) were included in the analysis of clinical efficacy . The median age was 47 years ( range , 20 - 64 ) . Allogeneic and autologous transplantations were performed in 56.0 % ( n = 140 ) and 44.0 % ( n = 110 ) of the patients , respectively . Baseline characteristics were well balanced between the two groups . Overall , the incidence of proven and probable IFIs within 100 days of HSCT was 7.6 % ( n = 19 ) . The percentages of patients who experienced proven or probable IFIs did not differ significantly between the micafungin and fluconazole groups : 7.3 % and 8.2 % , respectively ( p = 0.786 ) . Thirteen patients in the micafungin arm ( 7.9 % ) and eight patients in the fluconazole arm ( 9.4 % ) needed a change in antifungal agent before engraftment ( p = 0.824 ) . Mortality within 100 days after HSCT did not differ significantly between groups : 9.1 % vs 12.9 % in the micafungin and fluconazole arms , respectively ( p = 0.345 ) . CONCLUSION Micafungin is comparable to fluconazole for the prevention of IFIs in HSCT recipients Background The VIPP study compared valganciclovir prophylaxis with preemptive treatment  regarding efficacy , safety , and long-term graft outcome in cytomegalovirus (CMV)-positive ( R+ ) renal transplant recipients . Methods Multicenter , open-label , r and omized clinical study with a 12-month study phase and a follow-up of up to 84 months . Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function . Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater ( polymerase chain reaction ) and maintained over ≥14 days , followed by secondary prophylaxis . Patients were stratified by donor CMV IgG serostatus ( donor CMV IgG positive [D+]/R+ , donor CMV IgG negative [D−]/R+ ) . Results The 12-month results were reported previously ( Witzke et al Transplantation 2012 ) . The intent-to-treat/safety population comprised 148 patients in the prophylaxis ( 61.5 % D+/R+ ) and 151 patients in the preemptive group ( 52.3 % D+/R+ ) . Overall , 47 % patients completed the follow-up . Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 ( 11.5 % ; 95 % confidence interval [ 95 % CI ] , 6.8 - 17.8 % ] vs 39.7 % ; 95 % CI , 31.9 - 48.0 % ; P < 0.0001 and 4.7 % ; 95 % CI , 1.9 - 9.5 % vs 15.9 % ; 95 % CI , 10.5 - 22.7 % ; P = 0.002 ) . Incidences of graft loss ( 7.4 % vs 8.6 % ) , death ( 9.5 % vs 11.3 % ) , rejection ( 29.1 % vs 28.5 % ) , and renal function ( estimated glomerular filtration rate [ mean ± SD ] : 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m2 ) were not significantly different between prophylaxis and preemptive treatment . Tolerability was comparable between groups . Conclusions Prophylaxis was more effective than the preemptive approach , applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients . Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment 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 ABSTRACT Treatment of solid-organ transplant ( SOT ) patients with ganciclovir (GCV)-valganciclovir ( VGCV )  according to the manufacturer 's recommendations may result in over- or underexposure . Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing , achieving the area under the curve ( AUC ) therapeutic target . We conducted a two-arm , r and omized , open-label , 40 % superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection . Group A was treated according to the manufacturer 's recommendations . For group B , the dosing was adjusted based on target exposures using a Bayesian prediction model ( NONMEM ) . Fifty-three patients were recruited ( 27 in group A and 26 in group B ) . About 88.6 % of patients in group B and 22.2 % in group A reached target AUC , achieving the 40 % superiority margin ( P < 0.001 ; 95 % confidence interval [ CI ] difference , 47 to 86 % ) . The time to reach target 
    Output:
    
Our results show that although failure is reported in the studies , the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy .