***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 Administering  outpatient parenteral antimicrobial therapy in the community setting ( CoPAT ) is becoming more common with the increasing emphasis on controlling costs . However , few controlled trials have evaluated this treatment modality . Methods Using data from a recent r and omized trial comparing daptomycin with st and ard therapy ( semi-synthetic penicillin or vancomycin , each with initial low-dose gentamicin ) for Staphylococcus aureus bacteraemia and infective endocarditis ( SAB/IE ) , patient characteristics and outcomes were evaluated . Patients receiving their full course of therapy in the hospital setting were compared with those who received some portion outside of the hospital ( CoPAT ) . Results Among the 200 patients , 51.5 % received CoPAT . These patients were generally younger ( median age 50 versus 54 years , P = 0.028 ) . In the CoPAT group , there tended to be fewer patients with endocardial involvement ( 8.7 % versus 18.6 % , P = 0.061 ) and pre-existing valvular heart disease ( 7.8 % versus 15.5 % , P = 0.120 ) . CoPAT patients received longer therapy courses ( mean 25.4 versus 13.5 days , P < 0.001 ) and had higher rates of therapy completion ( 90.3 % versus 45.4 % , P < 0.001 ) and clinical success ( 86.4 % versus 55.7 % , P < 0.001 ) . Persisting or relapsing S. aureus was less frequent in the CoPAT group ( 3.9 % versus 15.5 % , P = 0.007 ) and there were fewer deaths ( 3.9 % versus 18.6 % , P = 0.001 ) 6 weeks after the end of therapy . Hospital readmission occurred for 18 of the 103 ( 17.5 % ) CoPAT patients . Clinical success rates were similar for CoPAT patients receiving daptomycin ( 90.0 % ) or st and ard therapy ( 83.0 % ) . Conclusions With proper monitoring , stable patients can complete treatment for SAB/IE as out patients in the community setting . Daptomycin is an appropriate option for this setting BACKGROUND The safety of adding initial low-dose gentamicin to antistaphylococcal penicillins or vancomycin for treatment of suspected Staphylococcus aureus native valve endocarditis is unknown . This study evaluated the association between this practice and nephrotoxicity . METHODS We performed a prospect i ve cohort study of safety data from a r and omized , controlled trial of therapy for S. aureus bacteremia and native valve infective endocarditis involving 236 patients from 44 hospitals in 4 countries . Patients either received st and ard therapy ( antistaphylococcal penicillin or vancomycin ) plus initial low-dose gentamicin ( n=116 ) or received daptomycin monotherapy ( n = 120 ) . We measured renal adverse events and clinical ly significant decreased creatinine clearance in patients ( 1 ) in the original r and omized study arms and ( 2 ) who received any initial low-dose gentamicin either , as a study medication or < or= days before enrollment . RESULTS Renal adverse events occurred in 8 ( 7 % ) of 120 daptomycin recipients , 10 ( 19 % ) of 53 vancomycin recipients , and 11 ( 17 % ) of 63 antistaphylococcal penicillin recipients . Decreased creatinine clearance occurred in 9 ( 8 % ) of 113 of evaluable daptomycin recipients , 10 ( 22 % ) of 46 vancomycin recipients , and 16 ( 25 % ) of 63 antistaphylococcal penicillin recipients . An additional 21 patients received initial low-dose gentamicin < or=2 days before study enrollment . A total of 22 % of patients who received initial low-dose gentamicin versus 8 % of patients who did not receive initial low-dose gentamicin experienced decreased creatinine clearance ( P = 005 ) . Independent predictors of a clinical ly significant decrease in creatinine clearance were age > or=65 years and receipt of any initial low-dose gentamicin . CONCLUSIONS Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely , given the minimal existing data supporting its benefit INTRODUCTION In a recent r and omized trial of Staphylococcus aureus bacteremia and native valve endocarditis , daptomycin was found not inferior to st and ard therapy . We summarized findings in the subgroup of patients with endocarditis according to the Duke criteria . METHODS Patients were r and omly assigned to receive daptomycin 6 mg/kg/day or st and ard therapy ( vancomycin 1 g every 12h or antistaphylococcal penicillin 2 g every 4h , both with gentamicin 1mg/kg every 8h for the first 4 days ) . The primary end point was success in the modified intent-to-treat population 6 weeks after the end of therapy . RESULTS Fifty-three patients were included : 35 with right-sided endocarditis ( RIE ) and 18 with left-sided endocarditis ( LIE ) . The success rates in patients with RIE were similar between daptomycin and the comparator ( 42 % vs 44 % ) . Patients with RIE with septic pulmonary infa rcts responded similarly to treatment with daptomycin and st and ard therapy ( 60 % vs 67 % ) . In the LIE population , treatment success rates were poor in both arms ( 11 % vs 22 % ) . CONCLUSION Daptomycin is an efficacious and well-tolerated alternative to st and ard therapy in the treatment of RIE . Patients with LIE had a poor outcome regardless of the treatment received . Daptomycin is also effective in treating endocarditis with septic pulmonary infa rcts BACKGROUND Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections , but the probabilities of target attainment ( PTA ) and toxicity of these doses have not been characterized in critically ill patients . METHODS We evaluated the plasma pharmacokinetics ( PK ) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6 - 8 mg/kg/day for primarily Staphylococcus species-related infections .  Daptomycin concentrations were measured intensively over the initial 96-hour dosing period . Data were modeled by population PK analyses , and Monte Carlo simulation was used to estimate the probabilities of effect and toxicity with st and ard and alternate dosing regimens . RESULTS Fifty patients with a mean ( SD ) age of 69.7 ( 12.2 ) years , weight 74.5 ( 20.3 ) kg , and creatinine clearance 56.8 ( 38.2 ) mL/minute were enrolled with measurements of 12 ( 2.2 ) daptomycin sample s per patient . Significantly lower  daptomycin exposures were observed despite comparable doses in a subset of patients ( n = 13 ) with augmented clearance ( CL ) . No covariates of CL were identified , but this subset was significantly more likely to be in severe sepsis or septic shock , have higher Sequential Organ Failure Assessment scores , and MRSA bacteremia . In-hospital mortality was significantly higher ( 30.7 % vs 10.8 % ) in patients with augmented daptomycin CL . Use of an empiric fixed dose of 750 mg of daptomycin is predicted to achieve a comparable PTA with a lower probability of toxicity as compared to the use of 10 mg/kg in critically ill patients . CONCLUSIONS A re appraisal of current daptomycin dosing recommendations is needed to improve the PTA and reduce toxicity among critically ill patients Daptomycin is the first available agent from a new class of antibiotics , the cyclic lipopeptides , that has activity against a broad range of gram-positive pathogens , including organisms that are resistant to methicillin , vancomycin , and other currently available agents . Daptomycin ( 4 mg/kg intravenously [ iv ] every 24 h for 7 - 14 days ) was compared with conventional antibiotics ( penicillinase-resistant penicillins [ 4 - 12 g iv per day ] or vancomycin [ 1 g iv every 12 h ] ) in 2 r and omized , international trials involving 1092 patients with complicated skin and skin-structure infections . Among 902 clinical ly evaluable patients , clinical success rates were 83.4 % and 84.2 % for the daptomycin- and comparator-treated groups , respectively ( 95 % confidence interval , -4.0 to 5.6 ) . Among patients successfully treated with iv daptomycin , 63 % required only 4 - 7 days of therapy , compared with 33 % of comparator-treated patients ( P<.0001 ) . The frequency and distribution of adverse events were similar among both treatment groups . Overall , the safety and efficacy of daptomycin were comparable with conventional therapy ABSTRACT The purpose of this paper is to establish the pharmacokinetics and safety of escalating , once-daily doses of daptomycin , a novel lipopeptide antibiotic active against gram-positive pathogens , including those resistant to methicillin and vancomycin . This phase 1 , multiple-dose , double-blind study involved 24 healthy subjects in three dose cohorts ( 4 , 6 , and 8 mg/kg of body weight ) who were r and omized to receive daptomycin or the control at a 3:1 ratio and administered the study medication by a 30-min intravenous infusion every 24 h for 7 to 14 days  .  Daptomycin pharmacokinetics was assessed by blood and urine sampling . Safety and tolerability were evaluated by monitoring adverse events ( AEs ) and laboratory parameters . Daptomycin pharmacokinetics was linear through 6 mg/kg , with a slight ( ∼20 % ) nonlinearity in the area under the curve and trough concentration at the highest dose studied ( 8 mg/kg ) . The pharmacokinetic parameters measured on the median day of the study period , ( day 7 ) were half-life ( ∼9 h ) , volume of distribution ( ∼0.1 liters/kg ) , systemic clearance ( ∼8.2 ml/h/kg ) , and percentage of the drug excreted intact in urine from 0 to 24 h ( ∼54 % ) . Daptomycin protein binding ( mean amount bound , 91.7 % ) was independent of the drug concentration . No gender effect was observed . All subjects who received daptomycin completed the study . The frequencies and distributions of treatment-emergent AEs were similar for the subjects who received daptomycin and the control subjects . There were no serious AEs and no pattern of dose-related events . The pharmacokinetics of once-daily administration of daptomycin was linear through 6 mg/kg . For all three doses , plasma daptomycin concentrations were consistent and predictable throughout the dosing interval . Daptomycin was well tolerated when it was administered once daily at a dose as high as 8 mg/kg for 14 days ABSTRACT The use of daptomycin in Gram-positive left-sided infective endocarditis ( IE ) has significantly increased . The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens . This was a prospect i ve cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus data base and the ICE-Daptomycin Sub study data base from 2008 to 2010 . Among patients with left-sided IE due to Staphylococcus aureus , coagulase-negative staphylococci , and Enterococcus faecalis , we compared those treated with daptomycin ( cohort A ) to those treated with st and ard-of-care ( SOC ) antibiotics ( cohort B ) . The primary outcome was in-hospital mortality . Time to clearance of bacteremia , 6-month mortality , and adverse events ( AEs ) ascribable to daptomycin were also assessed . There were 29 and 149 patients included in cohort A and cohort B , respectively . Baseline comorbidities did not differ between the two cohorts , except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin .  The median daptomycin dose was 9.2 mg/kg of body weight/day . Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen . In-hospital and 6-month mortalities were similar in the two cohorts . In cohort A , median time to clearance of methicillin-resistant S. aureus ( MRSA ) bacteremia was 1.0 day , irrespective of daptomycin dose , representing a significantly faster bacteremia clearance compared to SOC ( 1.0 versus 
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No significant difference was identified for all-cause mortality between the daptomycin and comparator groups ( RR = 1.17 , 95 % CI 0.76 - 1.79 ) but daptomycin therapy did reduce the duration of treatment .
Daptomycin caused a significantly lower incidence of renal impairment , nausea and headache but caused a reversible increase in creatine phosphokinase ( CPK ) .
Subgroup analysis indicated that daptomycin was significantly associated with a higher incidence of CPK elevation and fewer renal impairments among the population with a mean age ≤60 years and a dose of daptomycin ≥6 mg/kg/24 h.  CONCLUSIONS Daptomycin showed efficacy similar to the comparator regimens among the ITT population but lower efficacy among the CE population .
Fewer adverse effects in total , but more CPK elevation effects , were observed in patients treated with daptomycin