Table 2 Available data on meropenem pharmacokinetics in continuous renal replacement therapy
Study | Sieving coefficienta | Type of pharmacokinetic analysis | Total CL (l/hour)a | Vd (l/kg)a | Residual diuresis (ml/24 hours)a | Clinical outcome | Authors’ dose recommendation | Study limitations |
|---|---|---|---|---|---|---|---|---|
Spanish product information | N/A | N/R | 12.3 | 0.25 | Normal renal function | N/A | N/A | N/A |
Ververs and colleagues [16] | 0.63 ± 0.252 | Noncompartmental | 4.57 ± 0.89 | 0.37 ± 0.15 | Anuric (range 0 to 19 ml/24 hours) | 20 % survival. 100 % target attainment | 500 mg every 12 hours for sensible strains, shorter dosage interval for intermediate strains | No severity score reported, small sample size |
Bilgrami and colleagues [15] | 0.74 (0.71 to 0.77) | Noncompartmental | 6 (5.2-6.2) | 0.37 (0.32-0.46) | Oligoanuric | 70Â % survival. 100Â % target attainment | 1Â g every 8Â hours | High intensity used, not applicable to patients with standard CVVHF settings |
Krueger and colleagues [24] | 0.91 ± 0.1 | Two-compartment modeling | 4.98 ± 1.29 | 0.28 ± 0.07 | <500 | 62.5 % survival. 100 % target attainment for MIC = 4 mg/l, 75 % target attainment for MIC = 8 mg/l | 500 mg every 12 hours for susceptible bacteria | Heterogenic group with patients with cardiogenic shock |
Thalhammer and colleagues [18] | N/R | Noncompartmental | 8.62 ± 1.12 | 0.34 ± 0.03 | Anuric | 33.3 % survival. 100 % target attainment for MIC = 8 mg/l | 1 g every 8 hours | First-dose pharmacokinetics, no severity score reported, no septic shock |
Tegeder and colleagues [19] | 1.17 ± 0.11 | Noncompartmental | 3.12 ± 0.50 | 0.18 ± 0.03 (for a 70 kg adult, weight not reported) | Five anuric, four with urine output <300 ml/24 hours | Survival N/R, 100 % target attainment | 500 mg every 12 hours or 250 mg every 6 hours | No severity score reported |
Valtonen and colleagues [49] | N/R | Noncompartmental | 4.72 ± 2.69 | N/R | 111.8 ± 201.7 | Survival N/R, 83.3 % target attainment | 1 g every 12 hours | No report of Vd. First-dose pharmacokinetics. No septic shock, not applicable to critically ill patients |
|  | N/R | Noncompartmental | 5.71 ± 3.58 | N/R | 120.9 ± 204.7 | Survival N/R, 83.3 % target attainment | 1 g every 12 hours | No report of Vd. First-dose pharmacokinetics. No septic shock, not applicable to critically ill patients |
|  | N/R | Noncompartmental | 3.27 ± 2.30 | N/R | 120.9 ± 204.7 | Survival N/R, 83.3 % target attainment | 500 mg every 8 hours | No report of Vd. First-dose pharmacokinetics. No septic shock, not applicable to critically ill patients |
Robatel and colleagues [20] | 0.65 (39Â % CV) | Four-compartment modeling | 5.5 (38Â % CV) | 0.52 | Anuric | 46.7Â % survival. Pharmacokinetic target attainment N/R | 750Â mg every 8Â hours or 1.5Â g every 12Â hours | No severity score reported, no average total CRRT dose reported |
Langgartner and colleagues [21] | 0.97 (0.87 to 1.05), bolus 0.89 (0.79 to 0.93), CI | Noncompartmental | 4.32 (3.93 to 4.96), bolus 4.40 (3.58 to 5.58), CI | 0.43 (0.38 to 0.54) | N/R | 66.7Â % survival. 83.3Â % target attainment in CI, 66.6Â % target attainment in bolus | 500Â mg loading dose, 2Â g every 24Â hours CI | No severity score and residual renal function reported, no septic shock |
Seyler and colleagues [22] | N/R | Noncompartmental | 4.9 (2.1 to 14) (for a 70Â kg adult, weight N/R) | 0.45 (0.20 to 3.03) | N/R | Survival N/R, 81Â % target attainment | 1Â g every 8Â hours loading dose (first 48Â hours), dose reduction thereafter | CVVHDF and CVVHF data analyzed altogether. No severity score and residual renal function reported |
Giles and colleagues [23] | 0.95 ± 0.03 | Two-compartment modeling | 3.63 ± 0.95 | 0.38 ± 0.12 | N/R | 60 % survival, 60 % target attainment | 1 g every 12 hours | Small sample size. No residual renal function reported. |
|  | 0.91 ± 0.09 | Two-compartment modeling | 4.72 ± 1.69 | 0.31 ± 0.08 | N/R | 60 % survival, 60 % target attainment | 1 g every 12 hours | Small sample size. No residual renal function reported. |
Krueger and colleagues [17] | 1.06 | Two-compartment modeling | 3.28 ± 1.02 | 0.26 ± 0.09 | Anuric | 66.7 % survival, 100 % target attainment | 1 g every 12 hours | Heterogenic group with patients with cardiogenic shock. QD not reported |
Isla and colleagues [26] | 0.76 ± 0.10 | Noncompartmental | 9.0 ± 4.55 | 0.57 ± 0.29 | N/R, mean CrCL = 1.1 ml/minute | Survival N/R, 85.7 % target attainment | 500 mg every 6 hours | No septic shock. The study compares three groups with different CRRT modalities. No residual diuresis and CrCL estimation method reported |
|  | 0.85 ± 0.13 | Noncompartmental | 8.16 ± 3.43 | 0.37 ± 0.10 | N/R, mean CrCL = 23.5 ml/minute | Survival N/R, 57.1 % target attainment | 500 mg every 6 hours | No septic shock. CVVHDF and CVVHF data analyzed altogether. The study compares three groups with different CRRT modalities. No residual diuresis and CrCL estimation method reported |
|  | N/R | Noncompartmental | 63.90 ± 39.74 | 1.31 ± 0.9 | N/R, mean CrCL = 95.9 ml/minute | Survival N/R, 16.7 % target attainment | Doses >2 g every 8 hours | No septic shock. Mainly trauma patients. The study compares three groups with different CRRT modalities. No residual diuresis and CrCL estimation method reported |
Isla and colleagues [25] | 0.72 (6.3 % CV) | Two-compartment modeling | 8.04 (13 % CV) | 0.50 (10 % CV) | N/R, mean CrCL = 22 ml/minute | Survival N/R, target attainment N/R | CI of 700 mg/24 hours (MIC = 4 mg/l) or 1,400 mg/24 hours (MIC = 8 mg/l) in CrCL <10 ml/minute, higher doses when >10 ml/minute | No septic shock. CVVHDF and CVVHF data analyzed altogether. Different filters used. No residual diuresis and CrCL estimation method reported |
Meyer and colleagues [27] | 1.02 ± 0.26 | Noncompartmental | 7.76 | 0.54 | Anuric | Survived but with significant sequels. Pharmacodynamic target was attained | 1 g every 12 hours | Case report with limited comparability to other studies |