***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: CONTEXT Although acute renal failure ( ARF ) is believed to be common in the setting of critical illness and is associated with a high risk of death , little is known about its epidemiology and outcome or how these vary in different regions of the world . OBJECTIVES To determine the period prevalence of ARF in intensive care unit ( ICU ) patients in multiple countries ; to characterize differences in etiology , illness severity , and clinical practice ; and to determine the impact of these differences on patient outcomes . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study of ICU patients who either were treated with renal replacement therapy ( RRT ) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries . MAIN OUTCOME MEASURES Occurrence of ARF , factors contributing to etiology , illness severity , treatment , need for renal support after hospital discharge , and hospital mortality . RESULTS Of 29 269 critically ill patients admitted during the study period , 1738 ( 5.7 % ; 95 % confidence interval [ CI ] , 5.5%-6.0 % ) had ARF during their ICU stay , including 1260 who were treated with RRT . The most common contributing factor to ARF was septic shock ( 47.5 % ; 95 % CI , 45.2%-49.5 % ) . Approximately 30 % of patients had preadmission renal dysfunction . Overall hospital mortality was 60.3 % ( 95 % CI , 58.0%-62.6 % ) . Dialysis dependence at hospital discharge was 13.8 % ( 95 % CI , 11.2%-16.3 % ) for survivors . Independent risk factors for hospital mortality included use of vasopressors ( odds ratio [ OR ] , 1.95 ; 95 % CI , 1.50 - 2.55 ; P<.001 ) , mechanical ventilation ( OR , 2.11 ; 95 % CI , 1.58 - 2.82 ; P<.001 ) , septic shock ( OR , 1.36 ; 95 % CI , 1.03 - 1.79 ; P = .03 ) , cardiogenic shock ( OR , 1.41 ; 95 % CI , 1.05 - 1.90 ; P = .02 ) , and hepatorenal syndrome ( OR , 1.87 ; 95 % CI , 1.07 - 3.28 ; P = .03 ) . CONCLUSION In this multinational study , the period prevalence of ARF requiring RRT in the ICU was between 5 % and 6 % and was associated with a high hospital mortality rate Background Correct antibiotic dosing remains a challenge for the clinician . The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam  , administered as an extended infusion . Methods This was a prospect i ve , observational , pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center . Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion .  Serial blood sample s were collected to describe the antibiotic pharmacokinetics . Urine sample s were taken from a 24-hour collection to measure creatinine clearance . Relevant data were drawn from the electronic patient file and the intensive care information system . Results We obtained data from 61 patients and observed extensive pharmacokinetic variability . Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target ( 100 % f T > MIC ) , of which almost 80 % had a measured creatinine clearance > 130 mL/min . Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target . Seven out of nineteen patients ( 37 % ) displaying a creatinine clearance > 130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50 % f T > MIC . Conclusions In this large patient cohort , we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients . A large proportion of the patients without renal dysfunction , most of whom displayed a creatinine clearance > 130 mL/min , did not achieve the desired pharmacokinetic/pharmacodynamic target , even with the use of alternative administration methods . Consequently , these patients may be at risk for treatment failure without dose up-titration 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 Background In ICU patients with normal serum creatinine ( SCr ) , a state of increased renal drug excretion has been described ( creatinine clearance ≥130 ml/min/1.73 m2 ) , and named augmented renal clearance ( ARC ) . In ICU patients , the accuracy of GFR estimates is insufficient . However , in clinical practice , the physician has not at one ’s disposal patient measured creatinine clearance ( CrCl ) when prescribing . The primary objective of this study was to assess the accuracy of 4 formulas to estimate GFR ( Cockcroft-Gault ( CG ) , Robert , sMDRD , and CKD-EPI formulas ) with other covariates to detect ARC in ICU patients . Methods We enroled 360 consecutive ICU patients with normal SCr in this prospect i ve observational study conducted in a primary teaching hospital . Comparisons between CrCl values and 4 estimated GFR ( eGFR ) formulas were estimated . Results In these 360 patients , ARC was observed in 33 % of patients most of them trauma . Individual predictive values of equations were poor and the phenomenon increased in ARC subgroup . CG and CKD-EPI were more accurate to detect an ARC . Multivariable analysis showed that the best-fitting model included 3 factors independently correlated to ARC : trauma patients , cut-off values of age ≤58 years , and CKD-EPI more than 108 ml/min/1.73 m2 . Conclusions In ICU patients with normal SCr , eGFR formulas are imprecise in assessing CrCl . If measured CrCl must be ideally used to detect modifications of the renal function , in clinical practice , age , reason for admission , and CKD-EPI could be used as screening tool to identify ARC Our objective was to prospect ively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone . Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h ( total dose , 750 mg ) . For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus , a second drug was added ( ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus ) . Population pharmacokinetic studies of 58 patients demonstrated that this population h and led the drug differently from population s of volunteers . Multivariate logistic regression analysis ( n=47 patients ) demonstrated that only the age of the patient and the achievement of an area under the curve : minimum inhibitory concentration ratio of > or = 87 had a significant effect on eradication of the pathogen ( P<.001 ) . Achieving the breakpoint made the patient 4 times more likely to achieve eradication . The effect was greatest in patients > or = 67 years old Introduction The aim of this study was to explore changes in glomerular filtration ( GFR ) and renal tubular function in critically ill patients at risk of augmented renal clearance ( ARC ) , using exogenous marker compounds . Methods This prospect i ve , observational pharmacokinetic ( PK ) study was performed in a university-affiliated , tertiary-level , adult intensive care unit ( ICU ) . Patients aged less than or equal to 60 years , manifesting a systemic inflammatory response , with an expected ICU length of stay more than 24 hours , no evidence of acute renal impairment ( plasma creatinine concentration < 120 μmol/L ) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion . The following study markers were administered concurrently : sinistrin 2,500 mg ( Inutest ; Laevosan , Linz , Austria ) , p-aminohippuric acid ( PAH ) 440 mg ( 4 % p-aminohippuric acid sodium salt ; CFM Oskar Tropitzsch , Marktredwitz , Germany ) , rac-pindolol 5 or 15 mg ( Barbloc ; Alphapharm , Millers Point , NSW , Australia ) and fluconazole 100 mg ( Diflucan ; Pfizer Australia Pty Ltd , West Ryde , NSW , Australia ) . Plasma concentrations were then measured at 5 , 10 , 15 , 30 , 60 and 120 minutes and 4 , 6 , 12 and 24 hours post-administration . Non-compartmental PK analysis was used to quantify GFR , tubular secretion and tubular reabsorption . Results Twenty patients were included in the study . Marker administration was well tolerated , with no adverse events reported . Sinistrin clearance as a marker of GFR was significantly elevated ( mean , 180 ( 95 % confidence interval ( CI ) , 141 to 219 ) ml/min ) and correlated well with creatinine clearance ( r = 0.70 , P < 0.01 ) . Net tubular secretion of PAH , a marker of tubular anion secretion , was also elevated ( mean , 428 ( 95 % CI , 306 to 550 ) ml/min ) , as was net tubular reabsorption of fluconazole ( mean , 135 ( 95 % CI , 100 to 169 ) ml/min ) . Net tubular secretion of (S)- and (R)-pinodolol , a marker of tubular cation secretion , was impaired . Conclusions In critically ill patients at risk of ARC , significant alterations in glomerular filtration , renal tubular secretion and tubular reabsorption are apparent . This has implication s for accurate dosing of renally eliminated drugs See related commentary by De Waele and Carlier , http://ccforum.com/content/17/2/130 Introduction Improved methods to optimize drug dosing in the critically ill are urgently needed . Traditional prescribing culture involves recognition of factors that m and ate dose reduction ( such as renal impairment ) , although optimizing drug exposure , through more frequent or augmented dosing , represents an evolving strategy . Elevated creatinine clearance ( CLCR ) has been associated with sub-therapeutic antibacterial concentrations in the critically ill , a concept termed augmented renal clearance ( ARC ) . We aim ed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients , while also examining demographic , physiological and illness severity characteristics that may help identify this phenomenon . Methods This prospect i ve observational study was performed in a 30-bed tertiary level , university affiliated , adult intensive care unit . Consecutive traumatized and septic critically ill patients , receiving antibacterial therapy , with a plasma creatinine concentration ≤110 μmol/L , were eligible for enrolment . Pulse contour analysis ( Vigileo / Flo Trac ® system , Edwards Lifesciences , Irvine , CA , USA 
    Output:
    
An influence of ARC on antimicrobial pharmacokinetics has been observed , with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations .
Conclusion ARC is a prevalent condition in critically ill patients , especially in young people , with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl .
ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels , but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs .