Table 2 Pharmacodynamic targets of β-lactam antibioticsa
From: Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams
Antibiotics | PD targets | Percentage of patients achieving targets | References |
|---|---|---|---|
Meropenem, 1 g tid or 3 g/day CI | 40% f T > MIC, with f assumed to be 98%. CFR according to Mystic database | PTA for MIC = 2 mg/L: bolus 100%, CI 100% | Roberts et al., 2009 [24] |
PTA for MIC = 8 mg/L: bolus 70%, CI 100% | |||
CFR for EC: bolus 100%, CI 100% | |||
CFR for PA: bolus 40.6%, CI 100% | |||
Ceftazidime, 2 g | 70% T > 4 × EUCAST breakpoint of PA | 28% | Taccone et al., 2010 [23] |
Cefepime, 2 g | 70% T > 4 × EUCAST breakpoint of PA | 16% | |
Meropenem, 1 g | 40% T > 4 × EUCAST breakpoint of PA | 75% | |
Piperacillin/tazobactam, 4.5 g | 50% T > 4 × EUCAST breakpoint of PA | 44% | |
Imipenem 1 g tid or 2 g/day CI | 40% f T > MIC, with f assumed to be 80% | MIC = 2 mg/L bolus dosing 88%, CI 100% | Sakka et al., 2007 [31] |
MIC = 4 mg/L bolus 75%, CI 86% | |||
Piperacillin/tazobactam 4.5 g qid or 13.5 g CI | 50% f T > MIC. CFR according to Mystic database | PTA for MIC = 0.25 mg/L bolus 79.2%, CI 100% | Roberts et al., 2009 [46] |
PTA for MIC = 1 mg/L bolus 60%, CI 100% | |||
CFR for 18 g/day: bolus 53.4%, CI 92.5% | |||
CFR for 13.5 g/day: bolus 40%, CI 92.4% | |||
Cefpirome 2 g bid | 60% T > MIC | PTA for MIC = 4 mg/L: bolus 60%, CI (4 g/day) 100% | Lipman et al., 2001 [48] |
PTA for MIC = 16 mg/L: bolus 10%, CI (4 g/day) 50% | |||
Cefpirome 2 g tid | 60% T > MIC plasma and tissue | PTA for MIC = 4 mg/L: plasma 100%, tissue 100% | Sauermann et al., 2005 [51] |
PTA for MIC = 16 mg/L: plasma 87.5%, tissue 75% | |||
Cefpirome 2 g bid | 65% f T > MIC, with f assumed to be 90%. CFR according to EUCAST database | CFR for EC: bolus 99.9%, CI (4 g/day) 100% | Roos et al., 2007 [50] |
CFR for PA: bolus 56.1%, CI (4 g/day) 84.4% | |||
Cefepime 2 g | 60% T > MIC MIC = 8 mg/L (NCCLS break point of PA) | PTA with 1 g bid 45% PTA with 2 g bid 68% | Bonapace et al., 1999 [57] |
PTA for MIC = 4 mg/L: 1 g bid 68%, 2 g bid 89% | |||
Cefepime 2 g | 65% f T > MIC, with f assumed to be 90%. CFR according to Queensland Health Pathology Service | CFR for EC: 2 g bid 78.9%, CI (4 g/day) 96.9% | Roos et al., 2006 [60] |
CFR for PA: 2 g bid 54%, CI (4 g/day) 91.7% | |||
Ceftazidime 1 g every 4 hours | 100% T > 4 × MIC (isolated pathogens; if negative cultures 100% T > 16 mg/L) | Ceftazidime 47.8% PTA with 1 g every 3 hours 88.2% | Conil et al., 2007 [54] |
Cefepime 2 g tid | Cefepime 20% PTA with 1 g every 4 hours 88.2% | ||
Cefepime 2 g tid | 50% f T > MIC, with f assumed to be 85% | PTA for MIC = 8 mg/L 91.8% | Nicasio et al., 2009 [59] |
PTA for MIC = 32 mg/L 50.3% | |||
Cefepime 2 g (each 12 to 36 hours) | 50% T > MIC MIC = 8 mg/L | First dose 67%; steady-state 44% | Chapuis et al., 2010 [55] |
Ceftazidime 2 g tid | 100% T > 5 × MIC MIC = 8 mg/L (PA break point) | 10% | Young et al., 1997 [65] |
PTA for CI (6 g/day) 60% | |||
Ceftazidime 2 g tid or 6 g/day CI | 100% T > 5 × MIC MIC = 8 mg/L (PA break point) | Bolus 20% | Lipman et al., 1999 [68] |
CI 100% | |||
Ceftazidime 1.5 g tid or 4.5 g/day CI | T > 4 × MIC plasma and peritoneum (isolated pathogens) | Plasma: bolus dosing 100%, CI 100% | Buijk et al., 2002 [74] |
Peritoneum: bolus 88%, CI 100% | |||
Ceftazidime 2 to 6 g/day CI | 100% T > 5 × MIC MIC = 8 mg/L (PA break point) Target concentration 40 ± 10 mg/L | 35.9% | Aubert et al., 2010 [72] |
Percentage of time on target (mean) | |||
Meropenem 2 g tid or 3 g CI | T > MIC (isolated susceptible pathogens) | Bolus T = 100%; CI T = 100% | Thalhammer et al., 1999 [27] |
Meropenem 1 g tid | T > MIC (isolated pathogens) | T = 90.8% | de Stoppelaar et al, 2000 [19] |
T > 4 × MIC T = 52% | |||
Meropenem 1 g bid or 1 g tid | T > MIC (isolated pathogens) | T = 80.9% (Cr Cl > 50 mL/minute; 1 g tid) | Kitzes-Cohen et al, 2002 [21] |
T = 91.7% (Cr Cl < 50 mL/minute; 1 g bid) | |||
Imipenem 1 g tid | T > MIC (isolated sensitive [MIC ≤ 2 mg/L] pathogens) | T = 100%; T > 4 × MIC T = 87.5% | Novelli et al., 2005 [29] |
Meropenem 1 g tid | T > MIC (isolated sensitive [MIC ≤ 2 mg/L] pathogens) | T = 100%; T > 4 × MIC T = 87.5% | |
Meropenem 1 g tid (bolus or 3-hour infusion) or 2 g tid (3-hour infusion) | T > MIC | For MIC = 1 mg/L: 1 g tid bolus T = 74.7%, 1 g tid 3 hours T = 93.6%, 2 g tid 3 hours T = 98.6%s | Jaruratanasirikul et al., 2005 [20] |
For MIC = 16 mg/L: 1 g tid bolus T = 28.3%, 1 g tid 3 hours T = 37.8%, 2 g tid 3 hours T = 57.9% | |||
Meropenem 1 g tid | T > MIC | For MIC = 4 mg/L: plasma T = 87%, peritoneum T = 87% | Karjagin et al., 2008 [25] |
For MIC = 16 mg/L: plasma T = 55%, peritoneum T = 43% | |||
Imipenem 500 mg qid (30 minutes or 2-hour infusion) or 1 g qid (2-hour infusion) | T > MIC | For MIC = 1 mg/L: 500 mg qid 30 minutes T = 64.7%, 500 mg qid 2 hours T = 76.5%, 1 g qid 2 hours T = 93.4% | Jaruratanasirikul and Sudsai, 2009 [30] |
For MIC = 4 mg/L: 500 mg qid 30 minutes T = 20.3%, 500 mg qid 2 hours T = 17.7%, 1 g qid 2 hours T = 60.3% | |||
Piperacillin 3 g qid or 8 g/day CI | T > MIC | For MIC = 16 mg/L: bolus dosing T = 62%, CI T = 100% | Rafati et al., 2006 [40] |
For MIC = 32 mg/L: bolus T = 39%, CI T = 65% | |||
Cefepime 2 g bid | T > MIC MIC = 7 mg/L (MIC90 of PA) | T = 80% | Kieft et al., 1993 [53] |
Ceftazidime 2 g tid or 3 g/day CI | T > MIC MIC = 4 mg/L (MIC of one isolated PA) | Bolus T = 92%; CI T = 100% | Benko et al., 1996 [67] |
Ceftazidime 2 g tid or 60 mg/kg/day CI | T > MIC (isolated pathogens) | Bolus T = 92.9%; CI T = 100% | Hanes et al., 2000 [70] |