Antibiotic dosing recommendations in critically ill patients receiving new innovative kidney replacement therapy

BMC Nephrology

Table 2 Five β-lactam dosing recommendations in five modeled kidney replacement therapies

Antibiotic agent	PD target†	Dosing Recommendation in Five KRTs
Antibiotic agent	PD target†	1. Thrice-weekly HD¹	2. Daily HD¹	3. Sequential Therapy²	4. 9-hour PIKRT³	5. Extended PIKRT⁴
Cefepime	60% fT_> MIC	2 g LD, 1 g q24h post-HD			1 g q12h	2 g LD, 1 g q12h
Cefepime	60% fT_> MICx4	3 g LD, 2 g q12h post-HD			3 g LD, 1 g q6h	2 g q8h
Ceftazidime	60% fT_> MIC	1 g q24h post-HD			1 g q12h	1 g q12h
Ceftazidime	60% fT_> MICx4	2 g LD, 1 g q8h post-HD			2 g LD, 1 g q8h	2 g q8h
Imipenem	40% fT_> MIC	500 mg q12h post-HD			500 mg q12h	500 mg q8h
Imipenem	40% fT_> MICx4	750 mg q8h post-HD			1 g q8h	750 mg q6h
Meropenem	40% fT_> MIC	500 mg q24h post-HD			500 mg q12h	500 mg q12h
Meropenem	40% fT_> MICx4	1 g LD, 500 mg q12h post-HD			500 mg q8h	1 g q12h
Piperacillin/ tazobactam	50% fT_> MIC	4.5 g q12h post-HD			4.5 g q12h	3.375 g q8h
Piperacillin/ tazobactam	50% fT_> MICx4	4.5 g q8h post-HD or 3.375 g q6h post-HD			4.5 g q8h or 3.375 g q6h	4.5 g q6h

¹HD: 4-hour hemodialysis with dialysate flow rate (Qd) 300 ml/min; ²Sequential therapy: 4-hour hemodialysis with Qd 300 ml/min, then 20-hour ultrafiltration at 5 ml/min; ³PIKRT: prolonged intermittent kidney replacement therapy at Qd 100 ml/min; ⁴Extended PIKRT: 24-hour hemodialysis at Qd 50 ml/min
PD: pharmacodynamic; LD: loading dose
†40%,50% and 60% fT_> MIC or fT_> MICx4 denotes at least 40%, 50%, and 60% of time during each day of one week of antibiotic therapy that the free plasma drug concentration was greater than the target minimum inhibitory concentration (MIC) or four time of the target MIC; Piperacillin doses are the ones that attain both piperacillin efficacy targets and tazobactam efficacy target (i.e. 50% fT > threshold concentration of 4 mg/L); Susceptibility breakpoint MIC for P. aeruginosa was used (i.e. 8 mg/L for cefepime and ceftazidime, 2 mg/L for imipenem and meropenem, and 16 mg/L for piperacillin)
Doses are ones attaining efficacy target of either 40%,50% and 60% fT_> MIC or fT_> MICx4 in ∼90% of 5,000 virtual patients receiving each of 5 kidney replacement therapies; All doses are started after a HD session in settings 1–3. All doses above are given as a 0.5-hour intermittent infusion except piperacillin/tazobactam which may be administered as either 0.5-hour intermittent infusion or 4-hour extended infusion

ISSN: 1471-2369