***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 Ceftazidime demonstrates time-dependent killing , which is maximal at 4 x or 5 x MIC for the organism , consequently continuous infusion ( CI ) has been proposed to ensure adequate ceftazidime concentrations for the entire course of therapy . Severe intra-abdominal infections ( IAIs ) require surgical or percutaneous drainage for management , and ceftazidime is frequently prescribed . Cardiovascular or metabolic changes and renal or liver dysfunction may alter drug pharmacokinetics during severe IAIs , and no data exist on concentrations of ceftazidime reached in the peritoneal fluid . The objectives here were to determine the pharmacokinetics of ceftazidime during continuous and intermittent administration in patients with severe IAIs , and to measure the concentrations of ceftazidime in the peritoneal exu date .  Eighteen surgical patients with severe IAI and a creatinine clearance of > 30 mL/min were studied . A non-r and omized pilot study of six patients treated with CI alone was followed by a prospect i ve , r and omized comparative study of 12 patients . Pilot study patients received ceftazidime 1 g iv followed by a 4.5 g CI over 24 h. R and omized patients received either ceftazidime continuously as above or 1.5 g tds . Sample s for pharmacokinetic analyses were collected on days 2 and 4 .  Ceftazidime concentrations were determined by high-performance liquid chromatography . CI result ed in a mean serum concentration > 40 mg/L and a T > 4 x MIC for most pathogens encountered in severe IAIs for > 90 % of the course of therapy in both serum and peritoneal exu date . Eight-hourly administration result ed in T > 4 x MIC for most pathogens encountered in severe IAIs for > 90 % of the dosing interval , but in peritoneal exu date for only 44 % of the dosing interval . During CI , AUCs in the peritoneal exu date were c. 60 % of the concomitant serum AUCs . In critically ill surgical patients with severe IAIs , CI of ceftazidime result ed in more favourable concentrations in serum and peritoneal exu date than 8-hourly bolus infusion 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 OBJECTIVES Implementation of current pharmacodynamic knowledge could enhance clinical results , avoid resistance development and reduce treatment costs . In this open , r and omized , multicentre study , we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis ( AECB ) . METHODS Eighty-one patients ( 56 males , 25 females , age 65.3 + /- 10.1 years ) with AECB were included . A subgroup of 21 patients underwent pharmacokinetic and pharmacodynamic examination . The patients received either ceftazidime 2 g every 8 h ( C3 x 2 ) or ceftazidime 2 g as a loading dose , followed by ceftazidime 2 g over 7 h every 12 h ( C2 x 2 ) for 8 - 14 days . Clinical and bacteriological responses were monitored at day 8 or 9 , and 72 h after the end of therapy ( EOT ) . RESULTS At EOT , clinical success was recorded in 90 % and 90.2 % of clinical ly evaluable patients receiving C3 x 2 and C2 x 2 , respectively . Bacteriological success at EOT was achieved in 87.5 % and 90.2 % of evaluable patients treated with C3 x 2 and C2 x 2 , respectively . C(max ) ( mg/L ) varied between 168.9 + /- 34.1 and 144.0 + /- 9.8 in the C3 x 2 group , and between 60.1 + /- 34.1 and 54.2 + /- 30.4 at steady-state in the C2 x 2 group . Minimal concentrations were between 9.1 and 13.4 mg/L in the C3 x 2 group , and between 16.6 and 17.7 mg/L in the C2 x 2 group . Concentrations > 4 - 5 x MIC were seen in all pathogens , except Staphylococcus aureus , during 100 % of infusion time . CONCLUSION The 2 x 7 h infusion of ceftazidime 2 g ( C2 x 2 ) was clinical ly and bacteriologically as effective as the usual 3 x 2 g ceftazidime short-term infusion in the treatment of AECB , and demonstrated advantages in terms of pharmacodynamic parameters compared with the C3 x 2 regimen ABSTRACT Beta-lactams are regularly administered in intermittent short-term infusions . The percentage of the dosing interval during which free drug concentrations exceed the MIC ( fT > MIC ) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams . Therefore , administration by continuous infusion has gained increasing interest recently . We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose , compared to the st and ard regimen of intermittent short-term infusion , results in a superior probability of target attainment as assessed by the fT > MIC value of imipenem . In this prospect i ve , r and omized , controlled clinical study , patients received either a loading dose of 1 g/1 g imipenem and cilastatin ( as a short-term infusion ) at time zero , followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days ( n = 10 ) , or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days ( total daily dose , 3 g/3 g ; n = 10 ) . Imipenem concentrations in plasma were determined by using a vali date d liquid chromatography-t and em mass spectrometry assay . A two-compartment open model was employed for population pharmacokinetic modeling . We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40 % fT > MIC . The probability of target attainment by MIC for intermittent infusion was robust ( > 90 % ) up to MICs of 1 to 2 mg/liter . The corresponding value for continuous infusion was 2 to 4 mg/liter . Although all 20 patients had an fT > MIC of 100 % , 3 patients died . Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis . Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients Since the bactericidal effects of beta-lactam antibiotics are time dependent , the optimum strategy for their administration could be continuous infusion . In this prospect i ve , r and omised controlled trial to evaluate the clinical efficacy of continuous infusion therapy , we evaluated the outcomes for 40 septic critically ill patients who received piperacillin either continuously ( 2 g intravenously ( i.v . ) over 0.5 h as a loading dose followed by 8 g i.v . daily over 24 h ( n=20 ) ) or as an intermittent infusion ( 3 g i.v . every 6h over 0.5 h ( n=20 ) ) . Results from our study demonstrated that the clinical efficacy of piperacillin as a continuous infusion is superior to intermittent administration in critically ill patients .  Change in APACHE II scores from baseline at the end of the second , third and fourth days , respectively , were 4.1 , 5.1 and 5.2 for continuous infusion and 2.0 , 2.6 and 2.8 for intermittent infusion ( P < or = 0.04 ) . Considering minimum inhibitory concentrations ( MICs ) of 16 microg/mL and 32 microg/mL , the percentage of time for which piperacillin plasma concentrations were higher than the MIC ( % T > MIC ) was calculated for each patient in the two groups . For MICs of 16 microg/mL and 32 microg/mL , % T > MIC in the continuous infusion group was 100 % and 65 % of the dosing interval , respectively ; in the intermittent infusion group , % T > MIC was only 62 % and 39 % of the dosing interval . There was a significant relationship between clinical results and laboratory data . It was shown that the superiority of the clinical efficacy of continuous infusion could be related to piperacillin pharmacodynamics . Continuous infusion significantly reduced the severity of illness as demonstrated by APACHE II scores during therapy BACKGROUND Beta-lactam antibiotics are reported to exhibit time-dependent bactericidal activity . However , there are limited data on the clinical efficacy of ceftazidime administered by continuous infusion . OBJECTIVE The objective of this study was to compare the clinical efficacy of ceftazidime administered by continuous infusion and by intermittent infusion in the treatment of ventilator-associated pneumonia ( VAP ) caused by gram-negative bacteria . METHODS This was a retrospective chart review of patients with VAP caused by gram-negative bacteria who were treated with initial empiric ceftazidime therapy in the intensive care unit ( ICU ) over a 5-year period ( from June 2002 to June 2007 ) . The intermittent-infusion group received ceftazidime 2 g infused over 30 minutes every 12 hours ; the continuous-infusion group received a ceftazidime loading dose of 1 g over 30 minutes , followed by 2 g infused over 720 minutes every 12 hours . Data extracted from patients ' charts included sex , age , severity of the patient 's condition at ICU admission ( Acute Physiology and Chronic Health Evaluation II [ APACHE II ] score ) , diagnosis group , weight , creatinine clearance , MIC of the organism responsible for VAP , and severity of organ dysfunction at the time VAP was suspected ( Sepsis-related Organ Failure Assessment [ SOFA ] score ) . Each clinical history was review ed by 
    Output:
    
Conclusions No clinical advantage was observed for prolonged infusion β-lactams .