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. 2023 Jul 18;13:65. doi: 10.1186/s13613-023-01153-6

Table 4.

Available PK/PD data for new β-lactam/β-lactamase inhibitor combinations and cefiderocol

Antibiotic PK/PD index (preclinical studies) Molecular weight (Dalton) Protein binding (%) Half-life (hours) VD (liters) Renal clearancea Elimination rate in RRTb ELF/plasma ratio (%) CSF/plasma ratio (%) References
Ceftazidime–avibactam
 Ceftazidime fT > MIC > 50% 637 < 10

HA: 1.5–2

CIP: 4.8

HA: 14–17

CIP: 35

 80–90% 55%

HA: 35–52

CIP: 21–43

 20–40 [212–219]
 Avibactam fT > 1 mg/L > 50% 265 6–8

HA: 1.5–2

CIP: 4.1

HA: 15–25

CIP: 51

  > 95% 55%

HA: 35–42

CIP: 22

 32
Ceftolozane–tazobactam
 Ceftolozane fT > MIC > 35–40% 765 16–21 HA: 3.5

HA: 13–18

CIP: 20

  > 95% 66%

HA: 48–61

CIP: 50

 20 [146, 201, 204–209, 220–225]
 Tazobactam fT > 1 mg/L > 20% 322 30 HA: 2.3

HA: 18

CIP: 32

 80% 56%

HA: 44–63

CIP: 62

 20
Imipenem–relebactam
 Imipenem fT > MIC > 40% 317 20 HA: 1

HA: 24

CIP: 20

 63% 66–87% HA: 55 8.5 [226–230]
 Relebactam fAUC0-24/CMI > 8 366 22 HA: 1.2 HA: 19  > 90% 67–87% HA: 54 NA
Meropenem–vaborbactam
 Meropenem fT > MIC > 75% 437 2 HA: 1.2

HA: 19

CIP: 16–33

 40–60% 38% HA: 65 8–24 [231–240]
 Vaborbactam fAUC0-24/MIC > 9 297 33 HA: 1.6 HA: 20.5 75–95% 53% HA: 79 NA
Aztreonam–avibactam
 Aztreonam fT > MIC > 50% 435 56 HA: 2.3–2.8 HA: 20 80% 38% HA: 30 3–52 [218, 219, 241–243]
 Avibactam fT > 2–2.5 mg/L > 50% 265 8 HA: 1.5–2 HA: 22  > 95% 55%

HA: 35–42

CIP: 22

 32
Cefiderocol fT > MIC > 75% 752 40–60 HA: 2.7 HA: 18 90% 60%

HA: 22

CIP: 10–55

 4–68 [151, 244–253]

PK: pharmacokinetic; PD: pharmacodynamic; Vd: volume of distribution; RRT: renal replacement therapy; ELF: epithelial lining fluid; CSF: cerebrospinal fluid; MIC: minimal inhibitory concentration; AUC: area under the curve; HA: healthy adult; CIP: critically ill patient; NA: non-available

aUnchanged for all; b intermittent haemodialysis or continuous RRT