***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Introduction Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics . Continuous renal replacement therapy ( CRRT ) , which is commonly used in septic patients , may further contribute to pharmacokinetic changes . Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient population s in which different CRRT devices and techniques have been used . We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT . Methods This open , prospect i ve study enrolled consecutive patients treated with CRRT and receiving either meropenem ( MEM ) , piperacillin-tazobactam ( TZP ) , cefepime ( FEP ) or ceftazidime ( CAZ ) .  Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from sample s taken before ( t = 0 ) and 1 , 2 , 5 , and 6 or 12 hours ( depending on the β-lactam regimen ) after the administration of each antibiotic . Series of measurements were separated into those taken during the early phase ( < 48 hours from the first dose ) of therapy and those taken later ( > 48 hours ) . Results A total of 69 series of serum sample s were obtained in 53 patients  ( MEM , n = 17 ; TZP , n = 16 ; FEP , n = 8 ; CAZ , n = 12 ) . Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp . for the recommended time in 81 % of patients treated with MEM , in 71 % with TZP , in 53 % with CAZ and in 0 % with FEP . Accumulation after 48 hours of treatment was significant only for MEM . Conclusions In septic patients receiving CRRT , recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP , FEP and CAZ ; for these latter drugs , higher doses and /or extended infusions should be used to optimise serum concentrations 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 OBJECTIVE To Compare the clinical efficacy and safety of meropenem with a 3-hour extended infusion or conventional 30-minute infusion regimen in treatment of hospital acquired pneumonia ( HAP ) in intensive care unit ( ICU ) patients . METHODS An open-label r and omized controlled clinical trial was conducted . 100 HAP patients , admitted to ICU of Qilu Hospital of Sh and ong University , who needed meropenem therapy were enrolled from September 1st , 2012 to September 30th , 2013 . The patients were r and omly divided into two groups . Patients who did not conform to the study protocol were excluded . A total of 78 patients were included for the study of clinical efficacy evaluation , with 38 cases in study group , and 40 in control group . The patients in study group received intravenous 1 g of meropenem ( dissolved in 40 mL saline ) within 10 minutes , and followed by the remaining 750 mg by continuous intravenous infusion for 3 hours , and the treatment was repeated every 8 hours . The patients in control group received meropenem by injection of 1 g ( dissolved in 40 mL saline ) , i.e. by intravenous infusion within 30 minutes every 8 hours . This regime was carried out for at least 7 days . Clinical efficacy , bacterial clearance rate , improvement of critical illness scoring , and safety were observed and compared after meropenem withdrawal between two groups . RESULTS Compared with control group , the clinical cure rate and 28-day survival rate in study group were significantly increased [ clinical cure rate : 71.1 % ( 27/38 ) vs. 42.5 % ( 17/40 ) , χ² = 6.461 , P=0.011 ; survival rate : 81.6 % ( 31/38 ) vs. 60.0 % ( 24/40 ) , χ² = 4.364 , P=0.037 ] . The improvement of clinical pulmonary infection score ( CPIS ) and sequential organ failure assessment ( SOFA ) score in study group were more marked than those in control group ( difference of CPIS score : -3.47 ± 2.48 vs. -1.50 ± 2.48 , t=-3.513 , P=0.001 ; difference of SOFA score : -2.10 ± 2.38 vs. -1.00 ± 2.21 , t=-0.800 , P=0.037 ) . There were no significant differences in duration of meropenem treatment , acute physiology and chronic health evaluation II ( APACHEII ) score , procalcitonin ( PCT ) , duration of mechanical ventilation , ICU stay days , secondary infection , and bacterial clearance rate between two groups . The main adverse reactions observed were transient elevation of liver enzymes and diarrhea in both groups , but no significant difference in their incidence was found between study and control groups [ elevated liver enzymes : 28.9 % ( 11/38 ) vs. 30.0 % ( 12/40 ) , χ² = 0.010 , P=0.919 ; diarrhea : 7.9 % ( 3/38 ) vs. 10.0 % ( 4/40 ) , χ² = 0.000 , P=1.000 ] . CONCLUSIONS Compared with conventional regime of 30-minute infusion of meropenem in the treatment of HAP in ICU patients , the clinical efficacy can be improved , the severity of the disease can be reduced , the recovery of organ failure and long-term prognosis can be improved with 3 hour extended infusion of meropenem 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 The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy .  Previously , no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared . In patients , no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found , and the mean sieving coefficient/saturation coefficient value ( 0.80 + /- 0.12 ) was similar to the unbound fraction ( 0.79 + /- 0.08 ) . An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient 's creatinine clearance was higher . Likewise , the contribution of continuous renal replacement therapy to 
    Output:
    
According to the Grading of Recommendations Assessment , Development , and Evaluation tool , the quality of evidence for mortality was high .
INTERPRETATION Prolonged infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was associated with significantly lower mortality  than short-term infusion .