Review
Introduction
Purpose
Search strategy and results
PK/PD variability of beta-lactam antibiotics in the critically ill
Antibiotic | Patients | Dose | Vd (l/kg) | CL (ml/min) | T
½(h) | C
max(mg/ml) | AUC (mg·h/L) | MIC targeted (mg/L) | PD target achieved | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Cefepime | 12 | 2 g q12h | 0.34* | 123 | 3.2 | 346 | 4 | 77% T > MIC | [18] | |
19 | 2 g q8h | 0.36 | 88.2* | 3.37 | 68 | 310 | 32 | 34% T > 4xMIC | [20] | |
13 | 2 g q12h | 0.32* | 134 | 2.5 | 249 | [33] | ||||
7 | 2 g q12h | 0.47* | 125 | 3.42 | 305 | 7 | 80% T > MIC90
| [19] | ||
5 | 100% T > MIC90
| |||||||||
17 | 2 g q8h | 0.37 | 88.2* | 3.37 | 66.56 | 324.02 | [34] | |||
Ceftazidime | 15 | 2 g q8h | 0.81* | 151 | 4.75 | 277.31 | [21] | |||
12 | 2 g q8h | 0.27* | 3.48 | 124.4 | 331 | 4 | 92% T > MIC | [35] | ||
17 | 2 g q8h | 0.51 | 63.7* | 6.28 | 61.65 | 523.49 | [34] | |||
18 | 2 g q8h | 0.48 | 112* | 5.84 | 63 | 522 | 32 | 45% T > 4xMIC | [20] | |
10 | 2 g q8h | 0.23 | 112* | 1.98 | [36] | |||||
49 | 2 g q8h or 6 g CI/day | 0.67* | 91.3 | [22] | ||||||
Meropenem | 8 | 2 g q8h or | 0.38* | 156.7 | 2.4 | 110.1 | 193.8 | 100% T > MIC | [37] | |
7 | 2 g LD + 3 g CI/day | 0.37* | 128.3 | 117.5 | 100% T > MIC | |||||
16 | 1 g q8h | 0.43 | 130.9* | 2.05 | 35 | 132 | 8 | 57% T > 4xMIC | [20] | |
10 | 1 g q8h or 3 g CI/day | 0.32* | 226.7 | [23] | ||||||
10 | 1 g q8h | 0.39* | 191 | 2.13 | 46.6 | 99.5 | 0.25-1 | 100% T > MIC | [38] | |
Piperacillin | 8 | 12/1.5 g PIP/TAZ CI | 0.33 | 286.7 | 144 | [24] | ||||
8 | 4/0.5 PIP/TAZ q6h or q8h | 266.6 | ||||||||
27 | 4 g q6h | 0.38 | 141.4* | 2.58 | 123 | 469 | 64 | 33% T > 4xMIC | [20] | |
Ceftriaxone | 54 | 2 g qd | 0.28* | 14.7 | 9.6 | 8 | 16% T > MIC | [25] | ||
10 | 2 g qd | 0.28* | 41.3 | 6.4 | 204.9 | [30] | ||||
Ertapenem | 17 | 1 g CI/day | 0.21* | 43.2 | 4.15 | 90 | 418 | 2 | 25% T > MIC | [39] |
8 | 1 g qd | 0.85* | 200.5 | 5.7 | 94.1 | 317.7 | [26] | |||
Flucloxacillin | 10 | 0.29* | 150.2 | 2.45 | [27] |
PK alterations in acute kidney injury
Antibiotic | Patients | Dose | Renal replacement modalities | Pharmacokinetic data | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RRT | Dialyzer | Q
B(mL/min) | Q
UF(mL/min) | Q
DF(mL/h) |
C
max(mg/L) |
t
H(h) |
Vd(l/kg) | AUC (mg·h/L) |
CL
tot
(mL/min) |
CL
RRT(mL/min) | Sc/Sa | Ref. | |||
Cefepime | 4 | 2 g q8h | CVVH or CVVHD | PAN or PS | 140-250 | 16.7-35 | 500-1000 | 100.5 l | 4.6 | 0.6 | 111.5 | 27.2 | 0.76 | [67] | |
5 | 1-4 g q12h or q24h | CVVH | PAN | 150 | 16 | 44.6 - 94.9 | 12.9 | 0.46 | 834.7 -1,677.8 | 35.9 | 13 | 0.86 | [66] | ||
7 | 1-4 g q12h or q24h | CVVHDF | PAN | 150 | 17 | 857-1020 | 25.7 -90.8 | 8.6 | 0.34 | 344.9 -1,306.8 | 46.8 | 26 | 0.78 | ||
8 | 2 g q12h | CVVH or CVVHDF | AN69 | 150 | 25.7* | 1610* | 43 | 6.17 | 0.55 | 379 | 72.8* | [84] | |||
Ceftazidime | 12 | 2 g q8h | CVVH | PS | 143 | 47 | 58.2 | 4.3 | 0.52* | 344 | 98.7 | 32.1 | 0.69 | [70] | |
7 | 3 g q24h | CVVDHF | AN69 | 150 | 25 | 1000 | 4 | 0.27* | 2514 | 62 | 33.6 | 0.81 | [69] | ||
4 | 1-2 g q6h | CVVH or CVVHDF | AN69 or PS | 130-140 | 25 | 500-1000 | 53.9-112 | 6.4 | 0.67 | 35.5-333.8 | 5-65.6 | 0.93 | [82] | ||
12 | 2 g q12h | CVVH or CVVHDF | AN69 | 150 | 25.7* | 1610* | 78 | 7.74 | 0.37 | 536 | 36.4* | [84] | |||
Meropenem | 8 | 500 mg q12h | CVVH | AN69 | 10 | 26.7 | 39.5 | 3.63 | 105.3 | 82.94 | 24.42 | 0.91 | [71] | ||
5 | 1 g q12h | CVVH | AN69 | 150 | 16.7–33.3 | 5.16 | 0.39* | 246 | 4.3 | 1.96 | 0.93 | [86] | |||
5 | 1 g q12h | CVVDHF | AN69 | 150 | 16.7 – 25 | 1000-1500 | |||||||||
10 | 1 g q8h | High volume CVVH | AN69 | 250 | 66.7-100 | 56.6 | 4.3 | 0.2 | 166.5 | 100 | 58.3 | 0.93 | [72] | ||
15 | 0.5-1 g q8h or q12h | CVVHDF | AN 69 | 90-150 | 0.17-4.5 | 600-1500 | 5.1 | 0.47* | 75 | 26.7 | 0.65 | [87] | |||
5 | 0.5 g q12h | CVVH | PAN | 200 | 25-30 | 24.5 | 6.37 | 0.37 | 129.5 | 4.57 | 1.03 | 0.63 | [88] | ||
9 | 0.5 g q8h or q12h | CVVH | AN69 | 150-170 | 1.7-2.5 | 38.9 | 8.7 | 0.17* | 52 | 22 | 1.17 | [72] | |||
9 | 1 g Stat | CVVH | PS | 150 | 45.8 | 28.1 | 0.37* | 118 | 143.7 | 49.7 | 0.24 | [89] | |||
Piperacillin/ tazobactam | 6 | 4 g q12h/0.5 g q12h | CVVH | PS | 100 | 13.3 | 7.7/13.9 | 64.8/40.3 | [90] | ||||||
CVVHDF | 1000 | 6.7/11.6 | 84.3/52.2 | ||||||||||||
2000 | 6.1/9.4 | 91.3/62.5 | |||||||||||||
8 | 2 g/0.25 g or 4 g/0.5 g | CVVHD | AN69 | 150 | 1.3-3.3 | 1500 | 4.3/5.6 | 0.31/0.24 | 47/29.5 | 22/17 | 0.87/0.64 | [91] | |||
Ceftriaxone | 6 | 2-4 g q24h | CVVH | PA | 100-150 | 20-30 | 10.8 | 0.45* | 16.6 | 0.69 | [77] | ||||
Flucloxacillin | 10 | 4 g q8h | CVVH | PA | 169 | 57 | 139.1-179.7 | 4.9 | 0.69* | 568 | 117.2 | 0.21 | [79] |
Is there a role for beta-lactam TDM in the critically ill?
Do beta-lactams meet the traditional criteria for requiring TDM?
No. | Criteria |
---|---|
1 | Narrow therapeutic range/index |
2 | Drug toxicity may lead to hospitalization, irreversible organ damage, and even death |
3 | No clearly defined clinical parameter that allows dose adjustments |
4 | Correlation exists between serum concentration and efficacy as well as toxicity |
5 | Unpredictable relationship between dose and clinical outcome |
6 | Difficult to predict pharmacokinetics (e.g. non-linear pharmacokinetics) |