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 | |
 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, 204,205,206,207,208,209, 220,221,222,223,224,225] |
 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 | |
 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 | |
 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 | |
 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 |