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

BMC Nephrology

Table 3 Probability of neurotoxicity of MCS-driven cefepime dosing recommendation in five kidney replacement therapies

	KRT setting	PD target^†	MCS-driven Cefepime dosing recommendation	Probability of total concentration above neurotoxicity threshold at the end of each day during 1 week of therapy^£
	KRT setting	PD target^†	MCS-driven Cefepime dosing recommendation	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7
1	4-hour HD on Mon-Wed-Fri	60% fT > MIC	2 g LD, 1 g q24h post-HD	58.5%	10.0%	41.9%	10.7%	41.2%	51.9%	16.6%
1	4-hour HD on Mon-Wed-Fri	60% fT > MICx4	3 g LD, 2 g q12h post-HD	98.2%	84.7%	98.3%	85.1%	98.3%	98.4%	85.5%
2	4-hour HD daily	60% fT > MIC	2 g LD, 1 g q24h post-HD	1.9%	1.1%	1.1%	1.2%	1.3%	1.5%	1.5%
2	4-hour HD daily	60% fT > MICx4	3 g LD, 2 g q12h post-HD	62.9%	70.0%	70.6%	70.6%	70.6%	70.6%	70.6%
3	Sequential 4-hour HD & 20-hour UF	60% fT > MIC	2 g LD, 1 g q24h post-HD	0.7%	0.3%	0.3%	0.3%	0.4%	0.4%	0.4%
3	Sequential 4-hour HD & 20-hour UF	60% fT > MICx4	3 g LD, 2 g q12h post-HD	58.4%	65.7%	66.2%	66.3%	66.3%	66.3%	66.3%
4	Early 9-hour PIKRT^€ daily	60% fT > MIC	1 g q12h	58.1%	74.7%	77.4%	78.0%	78.2%	78.2%	78.2%
	Early 9-hour PIKRT^€ daily	60% fT > MICx4	2 g LD, 1 g q6h	99.9%	99.9%	99.9%	99.9%	99.9%	99.9%	99.9%
	Late 9-hour PIKRT^€ daily	60% fT > MIC	1 g q12h	1.6%	16.4%	23.2%	25.0%	25.6%	25.7%	25.8%
	Late 9-hour PIKRT^€ daily	60% fT > MICx4	2 g LD, 1 g q6h	81.6%	80.3%	80.3%	81.3%	80.3%	80.3%	80.3%
5	Extended PIKRT daily	60% fT > MIC	1 g q12h	2.1%	11.8%	16.4%	17.7%	18.1%	18.3%	18.4%
5	Extended PIKRT daily	60% fT > MICx4	2 g q8h	62.2%	67.9%	68.2%	68.2%	68.2%	68.2%	68.2%

KRT: kidney replacement therapy; PD: pharmacodynamic; MCS: Monte Carlo simulation; HD: Hemodialysis at dialysate flow rate (Qd) 300 ml/min; UF: Ultrafiltration at ultrafiltration flow rate of 5 ml/min; PIKRT: Prolonged intermittent kidney replacement therapy (9-hour PIKRT runs at Qd 100 ml/minl and extended PIKRT runs at Qd 50 ml/min for 24 h); LD: loading dose
^†60% fT_> MIC or 60% fT_> MICx4 denotes at least 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 of 8 mg/L (susceptibility breakpoint MIC for P. aeruginosa)
^£This indicates the percentage of 5000 simulated patients that were at or above the suggested cefepime neurotoxicity threshold (i.e. total plasma concentration ≥ 20 mg/L) at the end of each day during 1 week of therapy
^€ EARLY PIKRT is where the initial cefepime dose is infused at the beginning of 9-hour PIKRT and late PIKRT where the initial cefepime dose is given 15 h prior to 9-hour PIKRT

ISSN: 1471-2369