***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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    ***EXAMPLES*** 
    Input: A prospect i ve , r and omized pilot study was undertaken to compare the efficacy of continuous versus intermittent ceftazidime in ICU patients with nosocomial pneumonia .  Ceftazidime was administered either as a 3 g/day continuous infusion ( CI ) or an intermittent infusion ( II ) of 2 g every 8 h. In addition , all patients received concomitant once-daily tobramycin . The demographics of the evaluable patients ( n = 35 ) were similar between the groups : age ( years ) , CI 46 + /- 16 , II 56 + /- 20 ; Apache score , CI 14 + /- 4 , II 16 + /- 6 ; time ( days ) from admission to diagnosis , CI 9 + /- 6 , II 9 + /- 6 .  Clinical efficacy , defined as cure/improvement was similar between groups [ n ( % ) , CI 16/17 ( 94 ) , II 15/18 ( 83 ) ] , while microbiological response was also comparable [ n ( % ) , CI 10/13 ( 76 ) , II 12/15 ( 80 ) ] . Minimal inhibitory concentrations ( MICs ) for all isolates were measured throughout the treatment course ; there was no development of resistance during therapy for either regimen . While limited clinical data exist , our results suggest that the use of ceftazidime by CI administration maintains clinical efficacy , optimizes the pharmacodynamic profile and uses less antibiotic compared with the st and ard 2 g every 8 h intermittent dosing regimen The extreme pharmacokinetic behaviour of drugs sometimes observed in critically ill patients poses a significant threat to the achievement of optimal antibiotic treatment outcomes . Scant information on beta-lactam antibiotic therapeutic drug monitoring ( TDM ) is available . The objective of this prospect i ve study was to evaluate the practicality and utility of a beta-lactam TDM programme in critically ill patients .  TDM was performed twice weekly on all eligible patients at a 30-bed tertiary referral critical care unit .  Blood concentrations were determined by fast-throughput high-performance liquid chromatography ( HPLC ) assays and were available within 12h of sampling . Dose adjustment was instituted if the trough or steady-state blood concentration was below 4 - 5x the minimum inhibitory concentration ( MIC ) or above 10x MIC . A total of 236 patients were subject to TDM over an 11-month period . The mean+/-st and ard deviation age was 53.5+/-18.3 years . Dose adjustment was required in 175 ( 74.2 % ) of the patients , with 119 of these patients ( 50.4 % ) requiring dose increases after the first TDM . For outcome of therapy , 206 ( 87.3 % ) courses result ed in a positive treatment outcome and there were 30 ( 12.7 % ) treatment failures observed including 14 deaths and 15 courses requiring escalation to broader-spectrum agents ; 1 course was ceased due to an adverse drug reaction . Using binomial logistic regression , only an elevated Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( P<0.01 ) and elevated plasma creatinine concentration ( P=0.05 ) were found to be predictive of mortality . In conclusion , further research is required to determine definitively whether achievement of optimal beta-lactam pharmacodynamic targets improves clinical outcomes Introduction Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens . The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection , and to evaluate the safety of both dosing regimens . Methods Patients admitted to the interdisciplinary Intensive Care Unit ( ICU ) who suffered from severe infections and received meropenem were r and omized either in the Infusion group ( n = 120 ) or in the Bolus group ( n = 120 ) . Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours . Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours . Clinical and microbiological outcome , safety , meropenem-related length of ICU and hospital stay , meropenem-related length of mechanical ventilation , duration of meropenem treatment , total dose of meropenem , and ICU and in-hospital mortality were assessed . Results Clinical cure at the end of meropenem therapy was comparable between both groups ( 83.0 % patients in the Infusion vs. 75.0 % patients in the Bolus group ; P = 0.180 ) . Microbiological success rate was higher in the Infusion group as opposed to the Bolus group ( 90.6 % vs. 78.4 % ; P = 0.020 ) . Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success ( OR = 2.977 ; 95 % CI = 1.050 to 8.443 ; P = 0.040 ) . Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group ( 10 ( 7 to 14 ) days vs. 12 ( 7 to 19 ) days ; P = 0.044 ) as well as shorter duration of meropenem therapy ( 7 ( 6 to 8) days vs. 8 ( 7 to 10 ) days ; P = 0.035 ) and lower total dose of meropenem ( 24 ( 21 to 32 ) grams vs. 48 ( 42 to 60 ) grams ; P < 0.0001 ) . No severe adverse events related to meropenem administration in either group were observed . Conclusions Continuous infusion of meropenem is safe and , in comparison with higher intermittent dosage , provides equal clinical outcome , generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients 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 ) , was used to provide continuous cardiac index ( CI ) assessment over a single six-hour dosing interval . Urinary CLCR measures were obtained concurrently . Results Seventy-one patients contributed data ( sepsis n = 43 , multi-trauma n = 28 ) . Overall , 57.7 % of the cohort manifested ARC , although there was a greater prevalence in trauma ( 85.7 % versus 39.5 % , P < 0.001 ) . In all patients , a weak correlation was noted between CI and CLCR ( r = 0.346 , P = 0.003 ) . This was mostly driven by septic patients ( r = 0.508 , P = 0.001 ) , as no correlation ( r = -0.012 , P = 0.951 ) was identified in trauma . Those manifesting ARC were younger ( P<0.001 ) , male ( P = 0.012 ) , with lower acute physiology and chronic health evaluation ( APACHE ) II ( P= 0.008 ) and modified sequential organ failure assessment ( SOFA ) scores ( P = 0.013 ) , and higher cardiac indices ( P = 0.013 ) . In multivariate analysis , age ≤50 years , trauma , and a modified SOFA score ≤4 , were identified as significant risk factors . These had greater utility in predicting ARC , compared with CI assessment alone . Conclusions Diagnosis , illness severity and age , are likely to significantly influence renal drug elimination in the critically ill , and must be regularly considered in future study design and daily prescribing practice BACKGROUND Beta-lactam antibiotics are a commonly used treatment for severe sepsis , with intermittent bolus dosing st and ard therapy , despite a strong theoretical rationale for continuous administration . The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis . METHODS This was a prospect i ve , double-blind , r and omized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam , meropenem , and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong . The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration ( MIC ) on days 3 and 4 . The assessed clinical outcomes were clinical response 7 - 14 days after study drug cessation , ICU-free days at day 28 and hospital survival . RESULTS Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups .  Plasma antibiotic concentrations exceeded the MIC in 82 % of patients ( 18 of 22 ) in the continuous arm versus 29 % ( 6 of 21 ) in the intermittent arm ( P = .001 ) . Clinical cure was higher in the continuous group ( 70 % vs 43 % ; P = .037 ) , but ICU-free days ( 19.5 vs 17 days ; P = .14 ) did not significantly differ between groups . Survival to hospital discharge was 90 % in the continuous group versus 80 % in the intermittent group ( P = .47 ) . CONCLUSIONS Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure . This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints The st and ard mode of administration of piperacillin treatment is by intermittent infusion . However , continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity . In previous studies , we found a higher rate of clinical cure of  ventilator-associated pneumonia ( VAP ) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime . Therefore , the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam ( PIP/TAZ ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure . Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration ( MIC ) of 8 microg/mL [ 8/9 ( 88.9 % ) vs. 6/15 ( 40.0 % ) ; odds ratio (OR)=10.79 , 95 % confidence interval ( CI ) 1.01 - 588.24 ; P=0.049 ] or 16 microg/mL [ 7/8 ( 87.5 % ) vs. 1/6 ( 16.7 % ) ; OR=22.89 , 95 % CI 1.19 - 1880.78 ; P=0.03 ] . Thus , administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8 - 16 microg/mL in patients without renal failure Augmented renal clearance ( ARC ) is known to influence β-lactam antibiotic pharmacokinetics . This sub study of the BLING-II trial aim ed to explore the association between ARC and patient outcomes in a large r and omised clinical trial . BLING-II enrolled 432 participants with severe sepsis r and omised to receive β-lactam therapy by continuous or intermittent infusion .  An 8-h creatinine clearance ( CLCr ) measured on Day 1 was used to identify ARC , defined as CLCr ≥ 130 mL/min . Patients receiving any form of renal replacement therapy were excluded . Primary outcome was alive ICU-free days at Day 28 . Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation . A total of 254 patients were included , among which 45 ( 17.7 % ) manifested ARC [ median ( IQR ) CLCr 165 ( 144 - 198 ) mL/min ] . ARC patients were younger ( P < 0.001 ) , more commonly male ( P 
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Conclusions CI of beta-lactam antibiotics is associated with better cure rates and higher % fT > MIC when administered to critically ill patients with respiratory infections , but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections