***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: 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 Study Objective To determine whether critically ill patients receiving extended‐infusion ( EI ) piperacillin/tazobactam would have improved clinical outcomes compared with patients receiving intermittent infusions . Design Single‐center , open‐label , prospect i ve study . Setting Twenty‐two – bed intensive care unit ( ICU ) in a regional hospital in Hong Kong . Patients A total of 367 adults who had a diagnosis of either bacterial infection or neutropenic fever and had received treatment with piperacillin/tazobactam for at least 48 hours between December 1 , 2013 , and August 31 , 2015 . Intervention Patients were assigned to receive piperacillin/tazobactam as either a 4‐hour EI ( 182 patients [ EI group ] ) or a 30‐minute intermittent infusion ( 185 patients [ non – extended infusion ( NEI ) group ] ) . Measurements and Main Results All patients were followed for at least 14 days after treatment assignment . The primary outcome was the 14‐day mortality rate after initiation of piperacillin/tazobactam . Secondary outcomes included in‐hospital mortality rate , time to defervescence , duration of mechanical ventilatory support , length of ICU stay , and duration of hospital stay . Both groups demonstrated similar 14‐day mortality ( 11.5 % in the EI group vs 15.7 % in the NEI group , p=0.29 ) . The mean time to defervescence was significantly reduced in the EI group ( 4 days in the EI group vs 6 days in the NEI group , p=0.01 ) ; no significant differences between groups were noted in the other secondary outcomes . An Acute Physiology and Chronic Health Evaluation II score of 29.5 or higher was found to strongly predict 14‐day mortality ( p=0.03 ) by Classification and Regression Tree analysis . In the post hoc analyses , a 14‐day mortality benefit was demonstrated in patients in the EI group in whom infectious organisms were identified ( mortality rate 9.3 % in the EI group vs 22.4 % in the NEI group , p=0.01 ) and in whom respiratory tract infection was diagnosed ( mortality rate 8.9 % in the EI group vs 18.7 % in the NEI group , p=0.02 ) . Conclusion Both the EI and NEI groups demonstrated similar 14‐day mortality . Post hoc subgroup analysis revealed a mortality benefit in patients in the EI group who had infectious organisms identified or were diagnosed with respiratory tract infections STUDY OBJECTIVE To compare continuous versus intermittent administration of piperacillin-tazobactam with regard to clinical , microbiologic , and economic outcomes . DESIGN Prospect i ve , open-label controlled study SETTING Community teaching hospital . PATIENTS Ninety-eight hospitalized patients prescribed piperacillin-tazobactam .  INTERVENTION Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin-tazobactam  were switched to continuous infusion of this drug combination . Dosages varied in accordance with the type of infection and each patient 's renal function . Fifty-one other patients with similar demographics and types of infection received intermittent infusion with piperacillin-tazobactam . MEASUREMENTS AND MAIN RESULTS Clinical success rates were 94 % for the continuous-infusion group and 82 % for the intermittent-infusion group ( p=0.081 ) . Microbiologic success rates were 89 % for the continuous-infusion group and 73 % for the intermittent-infusion group ( p=0.092 ) . Days to normalization of fever were significantly lower ( p=0.012 ) in the continuous-infusion group ( 1.2 + /- 0.8 days ) than in the intermittent-infusion group ( 2.4 + /- 1.5 days ) . Level 1 and level 2 costs/patient were both reduced by continuous infusion , although the difference was statistically significant only for level 2 costs ( $ 399.38 + /- 407.22 for continuous infusion vs $ 523.49 + /- 526.85 for intermittent infusion , p=0.028 ) . CONCLUSION Continuous infusion of piperacillin-tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion . Compared with intermittent infusion , continuous infusion significantly shortened the time to temperature normalization , while also offering a significant reduction in level 2 expenditures 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 Morbidity and mortality for critically ill patients with infections remains a global healthcare problem . We aim ed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome . METHODS This was a prospect i ve , multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics . Two blood sample s were taken from each patient during a single dosing interval . The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration ( MIC ) of the pathogen at both 50 % ( 50 % f T > MIC ) and 100 % ( 100 % f T > MIC ) of the dosing interval . We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome . RESULTS We included 384 patients ( 361 evaluable patients ) across 68 hospitals . The median age was 61 ( interquartile range [ IQR ] , 48 - 73 ) years , the median Acute Physiology and Chronic Health Evaluation II score was 18 ( IQR , 14 - 24 ) , and 65 % of patients were male . Of the 248 patients treated for infection , 16 % did not achieve 50 % f T > MIC and these patients were 32 % less likely to have a positive clinical outcome ( odds ratio [ OR ] , 0.68 ; P = .009 ) . Positive clinical outcome was associated with increasing 50 % f T > MIC and 100 % f T > MIC ratios ( OR , 1.02 and 1.56 , respectively ; P < .03 ) , with significant interaction with sickness severity status . CONCLUSIONS Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure ; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients ABSTRACT The purpose of this r and omized , multicenter , open-label study was to compare the continuous infusion of piperacillin-tazobactam with the st and ard intermittent infusion in 262 hospitalized patients with complicated intra-abdominal infections . Within 1 day of surgical intervention , eligible patients were r and omized ( 1:1 ) to piperacillin-tazobactam  12 g/1.5 g administered continuously over 24 h or 3 g/0.375 g administered over 30 min intermittently every 6 h for 4 to 14 days . The demographics of the patients in the groups were similar , with a median APACHE II score of 7 and a median length of hospitalization of 7 days . Among 167 clinical ly evaluable patients , 86.4 % and 88.4 % of the patients treated with the continuous infusion and the intermittent infusion , respectively , were clinical ly cured or improved at the test-of-cure visit ( P = 0.817 ) . Bacteriological success was observed in 83.9 % and 87.9 % of patients ( P = 0.597 ) in the two groups , respectively , and no differences in bacteriological response by pathogen were noted . Defervesence and white blood cell count normalization occurred in the majority of patients within 3 days and were similar between patients receiving the continuous infusion and those receiving the intermittent infusion . Drug-related adverse events were generally 
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Conclusions : Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients