Table 3 Available data on piperacillin pharmacokinetics in continuous renal replacement therapy

Occhipinti and colleagues [28]

12

Healthy volunteers

N/A

N/A

Piperacillin 4.5 g every 8 hours

N/A

N/A

N/A

Arzuaga and colleagues [29]

4

Critically ill patients with sepsis and CrCL <10 ml/minute. SOFA 13.5 ± 3.1

Several

Target: 100 % T_>MIC for susceptibility and intermediate-susceptibility breakpoints (<32 mg/l and >64 mg/l)

Piperacillin/tazobactam 4.5 g every 6 to 8 hours

AN 69 HF, 0.9 m² copolymer filter

CVVHF

Q_R: 1.63 ± 0.47 l/hour

5

Critically ill patients with sepsis and CrCL 10 to 50 ml/minute. SOFA 11 ± 2.1

Several (60 % peritonitis)

Target: 100 % T_>MIC for susceptibility and intermediate-susceptibility breakpoints (<32 and >64 mg/l)

Piperacillin/tazobactam 4.5 g every 6 to 8 hours

AN 69 HF, 0.9 m² copolymer filter

CVVHF

Q_R: 1.82 ± 0.26 l/hour

5

Critically ill patients with sepsis and CrCL >50 ml/minute. SOFA 9 ± 1.4

Several (60 % VAP)

Target: 100 % T_>MIC for susceptibility and intermediate-susceptibility breakpoints (<32 and >64 mg/l)

Piperacillin/tazobactam 4.5 g every 6 to 8 hours

AN 69 HF, 0.9 m² copolymer filter

CVVHF

Q_R: 1.20 ± 0.45 l/hour

van der Werf and colleagues [30]

9

Critically ill patients with septic shock and MODS. APACHE II 30.1 ± 4.2

Several

Target: 100 % T_>MIC of the in vitro sensitivity of microbial isolates recovered from the infection site

Piperacillin/tazobactam 4.5 g every 8 hours

N/R

CVVHF

Q_R: 1.55 ± 0.59 l/hour

Capellier and colleagues [31]

10

Critically ill patients with septic shock (seven cases) or cardiogenic shock (three cases) and AKI. SAPS II score 74 ± 6

N/R

N/R

Piperacillin 4 g every 8 hours (six cases first dose, four cases steady state)

0.5 m² polysulphone filter

CVVHF

N/R

Asín-Prieto and colleagues [32]

Total: 16, N/R by degree of renal function

Critically ill patients with sepsis/polytrauma and different degrees of renal function (CrCL 1.3 to 110 ml/minute). SOFA 11 ± 3

N/R

Target: 100 % T_>MIC for the susceptibility breakpoint (16 mg/dl) (CLSI)

Piperacillin/tazobactam 4.5 g every 4, 6 and 8 hours (two, seven and seven cases, respectively)

AN 69 HF, 0.9 m² copolymer filter

CVVHF

Q_R: 1.54 ± 0.43 l/hour

Bauer and colleagues [33]

42

Critically ill patients with sepsis and AKI/end-stage renal disease. CCF score 7.9 ± 2.8

N/R

Target: 50 % T_>MIC for the susceptibility and intermediate-susceptibility breakpoint (16 and 64 mg/dl)

Piperacillin/tazobactam 2.25 to 3.375 g every 6, 8 and 12 hours

M60 to M100 HF, 0.6 to 0.9 m² acrylonitrile filter or NxStage System One, 1.5 m² polyethersulphone filter

CVVHD / CVVHDF

Q_T: 2.4 (for mean weight of 95 kg)

Mueller and colleagues [34]

8

Critically ill patients with sepsis and AKI. No severity score reported

Pneumonia

Target: 50 % T_>MIC for the susceptibility and intermediate-susceptibility breakpoint (16 and 32 mg/dl)

Piperacillin/tazobactam 4.5 g every 8, 12 and 24 hours (three, four and one cases, respectively)

AN 69 HF, 0.6 m² filter

CVVHD

Q_D: 1.5 l/hour, Q_R: 0.08 to 0.20 l/hour

Keller and colleagues [35]

12

Critically ill patients with sepsis and AKI. No severity score reported

Several

N/R

Piperacillin 4 g single dose (10 cases), 4 g every 8 hours (two cases)

AN 69 HF, 0.43 m² copolymer filter

CAVHD

Q_D: 1.22 ± 0.09 l/hour

Valtonen and colleagues [50]

6

Septic patients with AKI. No severity score reported

Several

Target: 100 % T_>MICPseudomonas spp. and Enterobacteriaceae spp. susceptibility breakpoint (16 mg/dl, BSAC)

Piperacillin/tazobactam 4.5 g every 12 hours

AV 400S, 0.7 m² polysulphone membrane

CVVHDF

Q_D: 1 l/hour, Q_R: N/R

CVVHDF

Q_D: 2 l/hour, Q_R: N/R

CVVHF

Q_R: N/R

Seyler and colleagues [22]

16

Critically ill patients with severe sepsis/septic shock and AKI. No severity score reported

N/R

Target: 50 % T_>4xMICPseudomonas aeruginosa susceptibility breakpoint (≤16 mg/l, EUCAST) (64 mg/l)

Piperacillin/tazobactam 4.5 g every 6 hours

AN 69 HF, type of membrane N/R

CVVHDF/CVVHF

Q_D: 0.023 ± 0.009 l/kg/hour (1.61 l/hour for a 70 kg adult, weight N/R), Q_R: 0.022 ± 0.012 l/kg/hour (1.54 l/hour for a 70 kg adult, weight N/R)

Varghese and colleagues [38]

10

Critically ill patients with severe sepsis/septic shock and AKI. APACHE II 33 (31 to 36), SOFA 12 (10 to 15)

N/R

Target: 50 % T_>MIC for clinically relevant MIC (2, 4, 8, 16, 32 and 64 mg/l) in plasma and subcutaneous tissue

Piperacillin/tazobactam 4.5 g every 8 hours

AN 69 HF, 1.05 m² polyacrylonitrile filter

CVVHDF

Q_D: 1 to 1.5 l/hour, Q_R: 1.5 to 2 l/hour, Q_T: 3.0 to 3.9 l/hour