***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: 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 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 Administration of β-lactam antibiotics by extended infusion optimizes the pharmacodynamic properties and bactericidal activity of these agents result ing in a potential improvement in patient outcomes and reduction in drug expenditure . Consequently , a pharmacist-led piperacillin-tazobactam extended 4-hour infusion guideline was implemented hospital-wide at a 500-bed academic medical center . Each piperacillin-tazobactam infusion was prospect ively monitored for 5 weeks to ensure accurate administration and identify barriers to guideline adherence . Overall , a total of 103 patients received 1215 doses of  piperacillin-tazobactam by extended infusions . In all , 98 % of the doses were administered at the correct extended infusion rate and 94 % of the doses were given at the scheduled time . There were a total of 20 missed doses and 53 delayed doses , accounting for 2 % and 4 % of the total administered doses , respectively . The primary barrier to adherence was the patient not being on the unit at the time of the scheduled dose followed by the piperacillin-tazobactam dose not being available on the floor . While insufficient power prevented meaningful evaluation of clinical outcomes , we anticipate a conservative annual estimated cost savings of $ 108 529 . Key elements contributing to our success included consistent pharmacy leadership , multidisciplinary involvement , thorough inservicing to health care professionals , hospital-wide implementation , and extensive quality assurance monitoring OBJECTIVES We investigated the population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam in hospitalized patients . PATIENTS AND METHODS A multicentre , r and omized clinical trial was conducted in hospitalized patients with complicated intra-abdominal infection . Patients received piperacillin/tazobactam administered by either continuous infusion ( 13.5 g over 24 h , n = 130 ) or intermittent infusion ( 3.375 g every 6 h , n = 132 ) . NONMEM was used to perform population pharmacokinetic analysis in a subset of patients ( n = 56 ) who had serum sample s obtained at steady-state for drug concentration analyses . Classification and regression tree analysis was used to identify the breakpoints of piperacillin PK-PD indexes in 94 patients with causative pathogen 's MIC . RESULTS A one-compartment model was applied to fit the data . Creatinine clearance and body weight were the most significant variables to explain patient variability in piperacillin and tazobactam  clearance and volume of distribution . The infusion method had no influence on PK parameters . For patients ( n = 30 ) receiving intermittent infusion in the pharmacokinetic study , mean Cmax and half-life were 122.22 mg/L and 1.17 h for piperacillin , and 15.74 mg/L and 1.81 h for tazobactam . For patients ( n = 26 ) receiving continuous infusion in the pharmacokinetic study , mean steady-state concentration was 35.31 + /- 12.15 mg/L for piperacillin and 7.29 + /- 3.28 mg/L for tazobactam . As a result of a low rate of failures ( < 11 % ) observed in the trial and the low MICs for infecting pathogens , no association could be established between clinical /microbiological outcome and drug exposure . CONCLUSIONS Intermittent infusion and continuous infusion of piperacillin and tazobactam provided sufficient drug exposure to treat those pathogens commonly implicated in intra-abdominal infections 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 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 mild and were reported in similar numbers of patients in each arm of the trial . The results of this study support continuous infusion as a safe and reasonable alternate mode of administration of piperacillin-tazobactam for the treatment of complicated intra-abdominal infection Background . There is an increasing movement towards the release of hospital “ report-cards . ” However , there is a paucity of research into the abilities of the different methods to correctly classify hospitals as performance outliers . Objective .To examine the ability of risk-adjusted mortality rates computed using conventional logistic regression and r and om-effects logistic regression models to correctly identify hospitals that have higher than acceptable mortality .  Research Design .Monte Carlo simulations . Measures .Sensitivity , specificity , and positive predictive value of a classification as a high-outlier for identifying hospitals with higher than acceptable mortality rates . Results .When the distribution of hospital-specific log-odds of death was normal , r and om-effects models had greater specificity and positive predictive value than fixed-effects models . However , fixed-effects models had greater sensitivity than r and om-effects models . Conclusions . Research ers and policy makers need to carefully consider the balance between false positives and false negatives when choosing statistical models for determining which hospitals have higher than acceptablemortality in performance profiling OBJECTIVE To observe the serum concentration and evaluate clinical efficacy of piperacillin/tazobactam ( TZP ) prolonged infusion time in treatment of hospital acquired pneumonia ( HAP ) . METHODS Fifty HAP patients admitted to intensive care unit ( ICU ) from March 1 to October 31 , 2012 were enrolled . The bacterial drug sensitivity results showed that the minimum inhibitory concentration ( MIC ) of TZP was 8 mg/L or 16 mg/L. According to completely r and omized grouping method , the patients were divided into treatment group ( n=25 ) and control group ( n=25 ) . The therapeutic regimen in control group was TZP 4.5 g , in regular infusion every 6 hours and finished in 30 minutes ; the treatment group was TZP 4.5 g , in prolonged infusion every 6 hours by using infusion pump for continuous intravenous infusion 3 hours . Acute physiology and chronic health evaluation II(APACHEII ) score , clinical pulmonary infection score ( CPIS ) and procalcitonin ( PCT ) level were compared between the two groups 3 days after treatment . The treatment success rate , remedial treatment rate , antibiotic costs were recorded in both groups . Blood specimen was collected at 0.5 , 1 , 2 , 3 , 4 , 6 hours at the beginning of administration , and the blood drug concentration of piperacillin and tazobactam  was determined using ultra performance liquid chromatography-t and em mass spectrometry ( UPLC-MS ) . RESULTS The PCT ( 2.16±0.17 μg/L 
    Output:
    
Conclusions Our systematic review and meta- analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy .
Data from this study could be extrapolated for other β-lactam antimicrobials .