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Table 3 Overview of dosing recommendations for ensuring appropriate pharmacodynamic exposure with some antimicrobial agents during CRRT

From: Bench-to-bedside review: Appropriate antibiotic therapy in severe sepsis and septic shock – does the dose matter?

Antibiotic Proposed optimal PD target versus susceptible pathogens Usual dosage recommendations Highest dosage recommendations Critical factors responsible for higher dosages
Meropenem Cmin > 4 mg/l 0.5 g q8 h to 0.5 q6 h 1 g q4–6 h Very high QUF >2 to 3 l/hour and/or QD >1 to 2 l/hour Significant residual renal function (CLCr >50 ml/minute) Borderline susceptible isolates (MICs of 8 to 16 mg/l)
Imipenem/cilastatin Cmin >4 mg/l 0.5 g q8 h to 0.5 g q6 h   
Flucloxacillin Cmin >4 mg/l 4 g q8 ha   
Piperacillin/tazobactam Cmin >16 to 64 mg/l 4.0/0.5 g q8 h 4.0/0.5 g q4 h Significant residual renal function (CLCr >50 ml/minute)
Cefepime Cmin >8 mg/l 1 to 2 g q12 h 2 g q8 h Very high QUF >2 to 3 l/hour and/or QD >1 to 2 l/hour Residual CLCr >50 ml/minute
Cefpirome Cmin >8 mg/l 1 g q12 h 2 g q8 h High non-CRRT related compensatory CL Adsorption to polysulfone haemofilter
Ceftazidime Cmin >8 mg/l 1 g q8 h or 3 g/day CI 2 to 3 q8 h Very high CLT (2- to 3-fold higher than in healthy volunteers)
Ceftriaxone Cmin >8 mg/l 2 g q24 h   
Teicoplanin Cmin = 10 to 20 mg/l LD 6 mg/kg q12 h for 4 doses MD 3 mg/kg q24 h LD 6 mg/kg q12 h for 4 doses MD 6 mg/kg q24 h Hypoalbuminaemia Significant residual renal function (CLCr >50 ml/minute)
Vancomycin Cmin = 15 to 20 mg/l 0.25 to 0.5 g q12 h 0.5 g q6 h Very high CRRT flow rates (QUF ± QD of 6 l/hour)
Ciprofloxacin Cmax/MIC >8 to 10 AUC/MIC >100 0.4 g q12 h   
Levofloxacin Cmax/MIC >8 to 10 AUC/MIC >100 0.5 g q48 h (or 0.25 q24 h) 0.5 g q24 h Very high QUF >3 l/hour
Moxifloxacin Cmax/MIC >8 to 10 AUC/MIC >100 0.4 g q24 ha   
Ofloxacin Cmax/MIC >8 to 10 AUC/MIC >100 0.4 g q8 ha   
Linezolid Cmin >4 mg/l 0.6 g q12 h 0.6 g q8 h Very high CLCRRT High non-CRRT-related CL in some critically ill patients
  1. aDosage recommendation from a single study. AUC, area under the plasma concentration-time curve; CI, continuous infusion; CLCr, creatinine clearance; CLCRRT, extracorporeal clearance; CLT, total body clearance; Cmax, peak plasma concentration; Cmin, trough plasma concentration; CRRT, continuous renal replacement therapy; CVVHDF, continuous venovenous haemodiafiltration; LD, loading dose; MD, maintenance dose; MIC, minimum inhibitory concentration; PD, pharmacodynamic; q × h, every × hours; QD, dialysate flow rate; QUF, ultrafiltration flow rate. Adapted with permission from Pea and coworkers [64].