***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 Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis . Hypotheses for this failure include possible hidden side-effects ( for example , neurological ) or inappropriate pharmacokinetic/pharmacodynamic ( PK/PD ) parameters for bacteria with cefepime minimal inhibitory concentrations ( MIC ) at the highest limits of susceptibility ( 8 mg/l ) or intermediate-resistance ( 16 mg/l ) for pathogens such as Enterobacteriaceae , Pseudomonas aeruginosa and Staphylococcus aureus . We examined these issues in a prospect i ve non-interventional study of 21 consecutive intensive care unit ( ICU ) adult patients treated with cefepime for nosocomial pneumonia . Methods Patients ( median age 55.1 years , range 21.8 to 81.2 ) received intravenous cefepime at 2 g every 12 hours for creatinine clearance ( CLCr ) ≥ 50 ml/min , and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute . Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography . PK/PD parameters were computed by st and ard non-compartmental analysis . Results Seventeen first-doses and 11 steady states ( that is , four to six days after the first dose ) were measured . Plasma levels varied greatly between individuals , from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations . Nineteen out of 21 ( 90 % ) patients had PK/PD parameters comparable to literature values . Twenty-one of 21 ( 100 % ) patients had appropriate duration of cefepime concentrations above the MIC ( T > MIC ≥ 50 % ) for the pathogens recovered in this study ( MIC ≤ 4 mg/l ) , but only 45 to 65 % of them had appropriate coverage for potential pathogens with cefepime MIC ≥ 8 mg/l . Moreover , 2/21 ( 10 % ) patients with renal impairment ( CLCr < 30 ml/minute ) demonstrated accumulation of cefepime in the plasma ( trough concentrations of 20 to 30 mg/l ) in spite of dosage adjustment . Both had symptoms compatible with non-convulsive epilepsy ( confusion and muscle jerks ) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest . Conclusions These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters ( for pathogens with upper-limit MICs ) in a population of ICU adult patients . Moreover , it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr ≥ 50 ml/minute infected by pathogens with cefepime MICs ≤ 4 mg/l . On the other h and , prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs EXECUTIVE SUMMARY Soft-tissue infections are common , generally of mild tomodest severity , and are easily treated with a variety ofagents . An etiologic diagnosis of simple cellulitis is fre-quently difﬁcult and generally unnecessary for patients with mild signs and symptoms of illness . Clinical as-sessment of the severity of infection is crucial , and sev-eral classiﬁcation schemes and algorithms have beenproposed to guide the clinician [ 1 ] . However , most clinical assessment s have been developed from eitherretrospective studies or from an author ’s own “ clinical experience , ” illustrating the need for prospect i ve studies with deﬁned measurements of severity coupled to man-agement issues and outcomes .Until then , it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity ( e.g.,fever or hypothermia , tachycardia [ heart rate Cefepime is administered as an intermittent infusion ( II ) ; however , continuous infusion ( CI ) may be advantageous because β-lactam antibiotics exhibit time-dependent antibacterial activity . This retrospective , non-r and omised , comparative study included 68 neurosurgical patients with post-operative intracranial infections treated with 4g/day cefepime over 24h as a CI ( n=34 ) or 2 g every 12h as II ( n=34 ) . CI  controlled the intracranial infection more rapidly and effectively than II ( 6.6±1.9 days vs. 7.8±2.6 days ; P=0.036 ) . By considering the minimum inhibitory concentrations ( MICs ) to be 4μg/mL and 8μg/mL , the percentage of time when the cefepime plasma or CSF concentrations were higher than the MIC ( % T > MIC ) was calculated for each patient . For plasma cefepime concentrations , the % T(>MIC ) in the CI group was higher than in the II group ( for MICs of 8μg/mL , 100 % vs. 75 % , respectively ) . The mean calculated area under the curve ( AUC ) in the CI group was similar to the II group ( 1197.99±72.15μgh/mL vs. 890.84±140.78μgh/mL ; P=0.655 ) . For CSF cefepime concentrations , the % T(>MIC ) in the CI group was higher than in the II group ( for MICs of 4μg/mL and 8μg/mL , 83.3 % and 75 % vs. 25 % and 0 % , respectively ) . The mean calculated AUC for the CI group was higher than the II group ( 220.56±13.59μgh/mL vs. 86.34±5.69μgh/mL ; P=0.003 ) . Therefore , CI of cefepime significantly enhanced the antibacterial effect and reduced the treatment duration in neurosurgical patients with post-operative intracranial infections Background : It is known that β-lactam antibiotics exhibit time-dependent bactericidal activity . Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration . However , limited data exist on the clinical efficacy of meropenem administered by continuous infusion . Objective : To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia ( VAP ) due to gram-negative bacilli . Methods : A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem . We analyzed 2 contemporary cohorts : one group received meropenem by continuous infusion ( 1 g over 360 min every 6 h ) , the other by intermittent infusion ( 1 g over 30 min every 6 h ) . The administration method was prescribed according to the physician 's discretion . Patients received meropenem plus tobramycin for 14 days . Results : There were no significant differences between patient groups with regard to gender , age , APACHE-II at intensive care unit admission , diagnosis , microorganism responsible for VAP , or organ dysfunction severity at the time VAP was suspected . The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion ( 38 of 42 , 90.47 % , vs 28 of 47 , 59.57 % , respectively , with OR 6.44 [ 95 % Cl 1.97 to 21.05 ; p < 0.001 ] ) . Conclusions : Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection . The prospect i ve r and omized parallel study was carried out in 50 patients with severe pneumonia ( n = 41 ) or bacteremia ( n = 9 ) . They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin . Patient characteristics and the minimal inhibitory concentration ( MIC ) of the isolated bacteria were comparable . Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups ( chi2 and Mann-Whitney U-tests ) . Mechanical ventilation , clinical outcome and bacteriological eradication did not significantly differ between the two groups . Also , the area under the plasma cefepime concentration curve at steady state ( AUCss : 612 + /- 369 vs. 623 + /- 319 mg x 1(-1 ) x h ) , AUCss > MIC ( 595 + /- 364 vs. 606 + /- 316 mg x 1(-1 ) x h ) and the area under the inhibitory concentration curve ( AUICss : 4258 + /- 5819 vs. 5194 + /- 7465 mg x 1(-1 ) x h ) were similar . If the time above MIC ( t > MIC ) was not significantly higher in Group 1 ( 100 + /- 0 % ) than in Group 2 ( 90 + /- 11 % ) , t > five-fold MIC in Group 1 ( 100 + /- 0 % ) was significantly higher ( p < 0.01 ) than in Group 2 ( 82 + /- 25 % ) . The mean time over the French breakpoint ( 4 mg/l ) was 100 + /- 0 % and 72 + /- 27 % in Group 1 and 2 ( p < 0.001 ) , respectively . In contrast to intermittent cefepime administration , continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens . This results in greater bactericidal activity against organisms with a higher ( 2 mg/l ) cefepime breakpoint even if the clinical outcome is not significantly modified We conducted a prospect i ve , open-label study to delineate a relationship between exposure and outcomes in 36 patients treated with cefepime . Twenty patients had documented Gram-negative infections .  Timed blood and urine sample s were obtained at steady state to determine pharmacokinetic and pharmacodynamic parameters . Microbiological success was significantly correlated with the proportion of the dosing interval that cefepime concentrations exceeded 4.3 x MIC . Our results support in vitro data that suggest bactericidal activity of beta-lactams is optimized at concentrations approximately 4 x MIC . These results should be vali date d by large prospect i ve clinical trials The objective of this study was to compare the pharmacokinetics of cefepime administered by continuous infusion and intermittent injection regimens . A prospect i ve , r and omized , cross-over study of ten patients with Gram-negative bacilli bacteraemia was conducted . All patients were r and omized to receive cefepime either as a 4-g continuous infusion over 24 h for 48 h or a 2-g bolus administered intermittently intravenously every 12 h for 48 h. After 48 h the patients received the alternative dose regimen .  Cefepime pharmacokinetic studies were carried out during hours 36 - 48 after the start of both regimens . All of the pathogens isolated from the blood in 7 patients had a minimum inhibitory concentration ( MIC ) < 1 microg mL(-1 ) . In both regimens , the serum cefepime concentrations at all time points were higher than the MIC for the pathogens isolated from this study . For the continuous infusion arm , the highest steady-state concentration was 49.80+/-18.40 microg mL(-1 ) and the lowest steady-state concentration was 41.42+/-16.48 microg mL(-1 ) . The steady-state concentrations were greater than 4 times the MIC of 8 microg mL(-1 ) . For the intermittent injection regimen , the mean trough concentration was 4.74+/-3.99 microg mL(-1 ) . The mean serum cefepime concentration was above 8 microg mL(-1 ) for 81.66 % of the dosing interval . Therefore , we conclude that either continuous infusion or intermittent injection can be used as an effective mode of cefepime administration to achieve bactericidal activity ABSTRACT The pharmacokinetics of a 2-g bolus of cefepime were measured in critically ill patients with normal renal function . Variable and low trough plasma drug concentrations were found , and 8 of 10 patients had levels below the MIC at which 50 % of the isolates are inhibited forPseudomonas aeruginosa . Computer simulations predicted that continuous infusion and shorter dosing intervals would increase trough levels ABSTRACT A population pharmacokinetic model of cefepime was constructed from data from adult critical care patients with ventilator-associated pneumonia ( VAP ) . A total of 32 patients treated with high-dose cefepime , 2 g every 8 h ( 3-h infusion ) or a renal function-adjusted equivalent dose , were r and omized into two groups—26 for the initial model and 6 for model validation . 
    Output:
    
Prolonged or continuous infusions of cefepime achieved the pharmacodynamic targets more often than traditional infusions .
The association of improved clinical outcomes with prolonged or continuous infusions is unclear .
Conclusions : The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets ; however , the effect on clinical outcomes is inconclusive .