Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration

Abstract

Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill 4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R 2 ‫؍‬ 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei.

How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

“…In these studies, CRRT caused more than 50% of meropenem CL total when a higher CRRT intensity was used (effluent flow rate N70 mL/min) (Bilgrami et al, 2010;Giles et al, 2000;Isla et al, 2005;Kielstein et al, 2006;Krueger et al, 1998Krueger et al, , 2003Langgartner et al, 2008;Robatel et al, 2003;Seyler et al, 2011;Tegeder et al, 1999;Thalhammer et al, 1998;Ververs et al, 2000). Substantial clearance of meropenem was also observed during PIRRT (Deshpande et al, 2010;Kielstein et al, 2006).…”

“…Doses between 2 and 3 g/day have resulted in mean or median meropenem trough concentrations that were above the susceptibility breakpoint of 2 mg/L in patients receiving CRRT (Bilgrami et al, 2010;Giles et al, 2000;Krueger et al, 1998;Langgartner et al, 2008;Robatel et al, 2003;Seyler et al, 2011). Higher dosing would be expected to be necessary for pathogens with higher MICs.…”

Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

“…Tables 1, 2, 3, 4, 5 and 6 summarize the available evidence on meropenem, piperacillin/tazobactam and ceftriaxone pharmacokinetics in critically ill patients with CRRT [15-38,49,50]. …”

Presence and Accuracy of Drug Dosage Recommendations for Continuous Renal Replacement Therapy in Tertiary Drug Information References

“…7 The information presented in its monographs is derived from pertinent references in the literature and expert therapeutic guidelines. 7 Notwithstanding the increasing body of literature concerning pharmacokinetic alterations during (Maintenance Dosage) Acyclovir 5-10 mg/kg IV NR 5-10 mg/kg IV q12-24h 5-10 mg/kg IV q24h q12-24h 6,18 Amikacin 5-7.5 mg/kg IV 4.5-10.5 mg/kg per day NR 7.5 mg/kg IV q24-72h q24-48h 6,19,20 IV divided q12-18h Amoxicillin 1000 mg PO q6h 19,21 NR NR NR Amphotericin, lipid complex 5 mg/kg IV q24h Imipenem-cilastatin 500 mg IV q6-8h 6,45 500 mg IV q6-8h 500 mg IV q6-8h 500 mg IV q6h Levofloxacin 250-750 mg IV/PO NR 250-750 mg IV/PO q24h 500 mg IV/PO q48h q24h 6,32,46 Linezolid 600 mg IV/PO q12h 47,48 NR NR 600 mg IV/PO q12h Meropenem 500-1000 mg IV 1000 mg IV q12h 500 mg IV q6-12h or 1000-2000 mg IV q12h q8-12h 6,[49][50][51][52][53][54][55][56] 1000 mg IV q8-12h Metronidazole 500 mg IV q6-12h 6,21 500 mg IV q6-12h NR 250-500 mg IV q8-12h Moxifloxacin 400 mg IV/PO q24h NR NR 3.1 g IV q8-12h Tobramycin 1-2.5 mg/kg IV 0.3-1.75 mg/kg 1-2.5 mg/kg IV q24-48h 1.7 mg/kg IV q24-48h q24-48h 6,19 IV q12h ‡ Vancomycin 7.5-15 mg/kg IV 500 mg IV q24-48h or 10-15 mg/kg IV 1000 mg IV q24-96h § q12-48h 6,37,[65][66][67][68][69] 1000 mg IV q48h § q24-48h or 7.5-10 mg/kg IV q12h Voriconazole 400 mg PO q12h × 2, NR No adjustment needed; 100% usual dosage then 200 mg PO q12h 13,…”