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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].