***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: 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 The pharmacodynamics and pharmacokinetics of ceftazidime administered by continuous infusion and intermittent bolus over a 4-day period were compared . We conducted a prospect i ve , r and omized , crossover study of 12 critically ill patients with suspected gram-negative infections . The patients were r and omized to receive ceftazidime either as a 2-g intravenous ( i.v . ) loading dose followed by a 3-g continuous infusion ( CI ) over 24 h or as 2 g i.v . every 8 h ( q8h ) , each for 2 days . After 2 days , the patients were crossed over and received the opposite regimen . Each regimen also included tobramycin ( 4 to 7 mg/kg of body weight , given i.v . q24h ) . Eighteen blood sample s were drawn on study days 2 and 4 to evaluate the pharmacokinetics of ceftazidime  and its pharmacodynamics against a clinical isolate of Pseudomonas aeruginosa ( R288 ) . The patient demographics ( means + /- st and ard deviations ) were as follows : age , 57 + /- 12 years ; sex , nine males and three females ; APACHE II score , 15 + /- 3 ; diagnosis , 9 of 12 patients with pneumonia . The mean pharmacokinetic parameters for ceftazidime given as an intermittent bolus ( IB ) ( means + /- st and ard deviations ) were as follows : maximum concentration of drug in serum , 124.4 + /- 52.6 micrograms/ml ; minimum concentration in serum , 25.0 + /- 17.5 micrograms/ml ; elimination constant , 0.268 + /- 0.205 h-1 ; half-life , 3.48 + /- 1.61 h ; and volume of distribution , 18.9 + /- 9.0 liters . The steady-state ceftazidime concentration for CI was 29.7 + /- 17.4 micrograms/ml , which was not significantly different from the targeted concentrations . The range of mean steady-state ceftazidime concentrations for the 12 patients was 10.6 to 62.4 micrograms/ml .  Tobramycin peak concentrations ranged between 7 and 20 micrograms/ml . As expected , the area under the curve for the 2-g q8h regimen was larger than that for CI ( P = 0.003 ) . For IB and CI , the times that the serum drug concentration was greater than the MIC were 92 and 100 % , respectively , for each regimen against the P. aeruginosa clinical isolate . The 24-h bactericidal titers in serum , at which the tobramycin concentrations were < 1.0 microgram/ml in all patients , were the same for CI and IB ( 1:4 ) . In the presence of tobramycin , the area under the bactericidal titer-time curve ( AUBC ) was significantly greater for IB than CI ( P = 0.001 ) . After tobramycin was removed from the serum , no significant difference existed between the AUBCs for CI and IB . We conclude that  CI of ceftazidime utilizing one-half the IB daily dose was equivalent to the IB treatment as judged by pharmacodynamic analysis of critically ill patients with suspected gram-negative infections . No evaluation comparing the clinical efficacies of these two dosage regimens was performed In an examination of the relationships among plasma aminoglycoside concentrations , the minimal inhibitory concentration ( MIC ) for the infecting organism , and therapeutic outcome , data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin , tobramycin , and amikacin .  Clinical response to therapy occurred in 188 ( 80 % ) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response ( P less than .00001 and P less than .0001 , respectively ) . A grade d dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy ABSTRACT Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections . This analysis was design ed to examine the relationship between drug exposure , as measured by the free-drug area under the concentration-time curve at 24 h (AUC24)/MIC ratio , and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving Streptococcus pneumoniae . The study population included 58 adult patients ( 34 males , 24 females ) who were enrolled in either of two phase III , r and omized , multicenter , double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis . Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC24s . In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines . Pharmacodynamic analyses were performed on data from all evaluable patients with documented S. pneumoniaeinfection using univariate and multivariable logistic regression ; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis . A statistically significant ( P = 0.013 ) relationship between microbiological response and the free-drug AUC24/MIC ratio was detected . At a free-drug AUC24/MIC ratio of < 33.7 , the probability of a microbiological response was 64 % , and at a free-drug AUC24/MIC ratio of > 33.7 , it was 100 % ( P < 0.01 ) . These findings may provide a minimum target free-drug AUC24/MIC ratio for the treatment of infections involving S. pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials . Further , when target free-drug AUC24/MIC ratios are used in conjunction with stochastic modeling techniques , these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and S.pneumoniae Objective The purpose of this study was to develop and vali date a model that predicts clearance and steady-state ceftazidime concentrations during continuous infusion . Design This was a prospect i ve clinical observational trial . Two models describing drug clearance during the continuous infusion of ceftazidime to infected patients were developed . The first model included inter- and intraindividual variability ( IIV ) while the second extended the first model by including interoccasional variability ( IOV ) . Setting This was a study of patients in a US hospital between January and June 1996 . Patients and participants The analysis included 39 patients aged > 18 years with infections at various sites . Interventions Patients received ceftazidime as either a 1000 or 2000 mg loading dose followed by a continuous infusion of 1000 to 4000 mg/day . Serum sample s were collected under approximate steady-state conditions and ceftazidime concentrations were analysed using high performance liquid chromatography . The models were fitted to the data using a nonlinear mixed effects model as implemented in the NONMEM program . Results 75 serum concentration measurements were included in the analysis . The routinely available clinical variables bodyweight , age , gender and serum creatinine were found to be statistically independent predictors of ceftazidime clearance . The IIV model was cross vali date d yielding a mean prediction error ( with a 95 % confidence interval ) of −0.51 mg/L ( −2.5 to 1.4 mg/L ) and a mean absolute prediction error of 6.5 mg/L ( 5.3 to 7.8 mg/L ) . Conclusion We have developed and vali date d a model to estimate ceftazidime concentrations during continuous infusion using commonly available clinical information . Additional work is needed to compare outcomes of patients receiving continuous and intermittently administered ceftazidime , and to define the optimal target steady-state ceftazidime concentrations during continuous infusion Seventy-four acutely ill patients were treated with intravenous ciprofloxacin  at dosages ranging between 200 mg every 12 h and 400 mg every 8 h. A population pharmacokinetic-pharmacodynamic analysis relating drug exposure ( and other factors ) to infectious outcome was performed . Plasma sample s were obtained and assayed for ciprofloxacin by high-performance liquid chromatography . Sample s from patients were frequently cultured so that the day of bacterial eradication could be determined . The pharmacokinetic data were fitted by iterative two-stage analysis , assuming a linear two-compartment model . Logistic regression was used to model ciprofloxacin exposure ( and other potential covariates ) versus the probabilities of achieving clinical and microbiologic cures . The same variables were also modelled versus the time to bacterial eradication by proportional hazards regression . The independent variables considered were dose , site of infection , infecting organism and the MIC for it , percent time above the MIC , peak , peak/MIC ratio , trough , trough/MIC ratio , 24-h area under the concentration-time curve ( AUC ) , AUC/MIC ratio ( AUIC ) , presence of other active antibacterial agents , and patient characteristics . The most important predictor for all three measures of ciprofloxacin pharmacodynamics was the AUIC . A 24-h AUIC of 125 SIT-1.h ( inverse serum inhibitory titer integrated over time ) was found to be a significant breakpoint for probabilities of both clinical and microbiologic cures . At an AUIC below 125 ( 19 patients ) , the percent probabilities of clinical and microbiologic cures were 42 and 26 % , respectively . At an AUIC above 125 ( 45 patients ) , the probabilities were 80 % ( P < 0.005 ) and 82 % ( P < 0.001 ) , respectively . There were two significant breakpoints in the time-to-bacterial-eradication data . At an AUIC below 125 ( 21 patients ) , the median time to eradication exceeded 32 days ; at an AUIC of 125 to 250 ( 15 patients ) , time to eradication was 6.6 days : and at AUIC above 250 ( 28 patients ) , the median time to eradication was 1.9 days ( groups differed ; P < 0.005 ) . These findings , when combined with pharmacokinetic data reported in the companion article , provide the rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients ' pharmacokinetics and their bacterial pathogens ' susceptibilities . An a priori dosing algorithm ( based on MIC , patient creatine clearance and weight , and the clinician-specified AUIC target ) was developed . This approach was shown , retrospectively , to be more precise than current guidelines , and it can be used to achieve more rapid bacteriologic and clinical responses to ciprofloxacin , as a consequence of targeting the AUIC Abstract One hundred and thirty-nine febrile episodes in 120 patients were treated with sisomicin after a combination of carbenicillin and a cephalosporin antibiotic had failed . These patients were r and omized to receive sisomicin either by continuous or by intermittent infusion . The response rate for patients treated with sisomicin was 61 percent by continuous infusion 
    Output:
    
In conclusion , the review ed data suggest that the continuous intravenous infusion of antibacterials with time-dependent bacterial killing seems to be superior than the intermittent intravenous administration , from a pharmacodynamic point of view , at least when treating bacteria with high MIC values for the studied antibacterials