ECMO Dosing Table

LogP Protein Vd
Binding Citation
Class: Beta Lactams
Gijsen M, Annaert P, Shekar K, Roberts JA, Wauters
J, Spriet I. Letter to the Editor regarding: Ceftriaxone
exposure in patients undergoing extracorporeal
membrane oxygenation. Int J Antimicrob Agents.
2021;57(5):106326.
doi:10.1016/j.ijantimicag.2021.106326
Ceftriaxone
CLSI breakpoint
(-)1.7 (Gijsen, 85%-95% 12-14 L
(enterobacterales): 1 Shekar K, Roberts JA, Welch S, et al. ASAP ECMO:
et al) (Lexicomp) (Lexicomp)
ug/mL Antibiotic, Sedative and Analgesic Pharmacokinetics
during Extracorporeal Membrane Oxygenation: a
EUCAST breakpoint: multi-centre study to optimise drug therapy during
ECMO. BMC Anesthesiol. 2012;12:29. Published
2012 Nov 28. doi:10.1186/1471-2253-12-29
Cefepime
(-)0.1 ~20% 0.26 L/kg
CLSI breakpoint
(Pubchem) (Lexicomp) (Lexicomp)
(pseudomonas): 8 ug/mL
Dhanani JA, Lipman J, Pincus J, et al.

Pharmacokinetics of Total and Unbound Cefazolin
during Veno-Arterial Extracorporeal Membrane
Oxygenation: A Case Report. Chemotherapy.
2019;64(3):115-118. doi:10.1159/000502474
Cefazolin
0.2 L/kg
CLSI breakpoint (-)0.6 (Booke, 60-92%
(Booke, et Booke H, Frey OR, Röhr AC, et al. Excessive unbound
(enterobacterales): 16 et al) (Booke, et al) cefazolin concentrations in critically ill patients
al)
ug/mL receiving veno-arterial extracorporeal membrane
oxygenation (vaECMO): an observational study. Sci
Rep. 2021;11(1):16981. Published 2021 Aug 20.
doi:10.1038/s41598-021-96654-4
Cheng V, Abdul-Aziz MH, Burrows F, et al.

Population Pharmacokinetics of Piperacillin and
Tazobactam in Critically Ill Patients Receiving
Extracorporeal Membrane Oxygenation: an ASAP
ECMO Study. Antimicrob Agents Chemother.
2021;65(11):e0143821. doi:10.1128/AAC.01438-21
Donadello K, Antonucci E, Cristallini S, et al. β-

Lactam pharmacokinetics during extracorporeal
membrane oxygenation therapy: A case-control
Piperacillin: study. Int J Antimicrob Agents. 2015;45(3):278-282.
26-33% 0.243 L/kg
-0.26 to 0.67 doi:10.1016/j.ijantimicag.2014.11.005
(Lexicomp) (Lexicomp)
(Drugbank)
Piperacillin-tazobactam
CLSI breakpoint
(pseudomonas): 16/4
ug/mL
Piperacillin:
26-33% 0.243 L/kg
-0.26 to 0.67
(Drugbank)
Kühn D, Metz C, Seiler F, et al. Antibiotic

therapeutic drug monitoring in intensive care
patients treated with different modalities of
extracorporeal membrane oxygenation (ECMO) and
Piperacillin-tazobactam renal replacement therapy: a prospective,
observational single-center study. Crit Care.
CLSI breakpoint 2020;24(1):664. Published 2020 Nov 25.
(pseudomonas): 16/4 doi:10.1186/s13054-020-03397-1
ug/mL
Fillâtre P, Lemaitre F, Nesseler N, et al. Impact of

extracorporeal membrane oxygenation (ECMO)
support on piperacillin exposure in septic patients: a
case-control study. J Antimicrob Chemother.
2021;76(5):1242-1249. doi:10.1093/jac/dkab031
Tazobactam: Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

31-32% 18.2 L Therapeutic drug monitoring and adequacy of
-1.4 to -1.8 current dosing regimens of antibiotics in patients on
(Drugbank) Extracorporeal Life Support. Anaesth Crit Care Pain
Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015

renal replacement therapy: a prospective,
2020;24(1):664. Published 2020 Nov 25.
doi:10.1186/s13054-020-03397-1
Seddon MM, Busey KV, Kutner SB, Mejia RE,

Oxacillin 94.2% +/- 13 Bhattacharyya R. Oxacillin therapeutic drug
monitoring in a patient on extracorporeal
CLSI breakpoint 2.38 (Seddon) 2.1% L/1.73m^2 membrane oxygenation support. J Antimicrob
(staphylococcus): 2 ug/mL (Seddon) (Seddon) Chemother. 2020;75(9):2699-2700.
doi:10.1093/jac/dkaa216
(-)0.86 to -3.8 20% 0.23-0.31

(Drugbank) (Lexicomp) L/kg Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:
(Lexicomp) Therapeutic drug monitoring and adequacy of
current dosing regimens of antibiotics in patients on
Extracorporeal Life Support. Anaesth Crit Care Pain
Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
Chen W, Zhang D, Lian W, et al. Imipenem

Population Pharmacokinetics: Therapeutic Drug
Monitoring Data Collected in Critically Ill Patients
with or without Extracorporeal Membrane
Imipenem-cilastatin Oxygenation. Antimicrob Agents Chemother.
CLSI breakpoint 2020;64(6):e00385-20. Published 2020 May 21.
(pseudomonas): 2 ug/mL doi:10.1128/AAC.00385-20
Imipenem-cilastatin
CLSI breakpoint
(pseudomonas): 2 ug/mL
Jaruratanasirikul S, Boonpeng A, Nawakitrangsan M,

Samaeng M. NONMEM population
pharmacokinetics and Monte Carlo dosing
simulations of imipenem in critically ill patients with
life-threatening severe infections during support
with or without extracorporeal membrane
oxygenation in an intensive care
unit. Pharmacotherapy. 2021;41(7):572-597.
doi:10.1002/phar.2597
(-)2.4 ~2% 15-20 L Donadello K, Antonucci E, Cristallini S, et al. β-

Lactam pharmacokinetics during extracorporeal
(PubChem) (Lexicomp) (Lexicomp) membrane oxygenation therapy: A case-control
study. Int J Antimicrob Agents. 2015;45(3):278-282.
doi:10.1016/j.ijantimicag.2014.11.005
Hanberg P, Öbrink-Hansen K, Thorsted A, et al.

Population Pharmacokinetics of Meropenem in
Plasma and Subcutis from Patients on
Extracorporeal Membrane Oxygenation Treatment.
Antimicrob Agents Chemother. 2018;62(5):e02390-
17. Published 2018 Apr 26. doi:10.1128/AAC.02390-
17
Meropenem
Shekar K, Fraser JF, Taccone FS, et al. The combined
CLSI breakpoint effects of extracorporeal membrane oxygenation
(pseudomonas): 2 ug/mL and renal replacement therapy on meropenem
pharmacokinetics: a matched cohort study. Crit
Care. 2014;18(6):565. Published 2014 Dec 12.
doi:10.1186/s13054-014-0565-2

2020;24(1):664. Published 2020 Nov 25.
doi:10.1186/s13054-020-03397-1
Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

Cefotaxime Therapeutic drug monitoring and adequacy of
CLSI breakpoint (-) 1.4 31-50% current dosing regimens of antibiotics in patients on
??
(enterobacterales): 1 (PubChem) (Lexicomp) Extracorporeal Life Support. Anaesth Crit Care Pain
Med. 2019;38(5):493-497.
ug/mL doi:10.1016/j.accpm.2019.02.015
Ceftazidime renal replacement therapy: a prospective,
CLSI breakpoint observational single-center study. Crit Care.
<10%
(pseudomonas, 0.4 (PubChem) ?? 2020;24(1):664. Published 2020 Nov 25.
(Lexicomp) doi:10.1186/s13054-020-03397-1
enterobacterales): 8
ug/mL, 4 ug/mL
~20%
Ceftaroline 2.3 (PubChem) 20.3 L
(Lexicomp)
Class: Antifungals
Spriet I, Annaert P, Meersseman P, et al.
Pharmacokinetics of caspofungin and voriconazole
in critically ill patients during extracorporeal
membrane oxygenation. J Antimicrob Chemother.
2009;63(4):767-770. doi:10.1093/jac/dkp026
Voriconazole 58% 4.6 L/kg

1.5 (PubChem)
Ruiz S, Papy E, Da Silva D, et al. Potential

voriconazole and caspofungin sequestration during
extracorporeal membrane oxygenation. Intensive
Care Med. 2009;35(1):183-184.
doi:10.1007/s00134-008-1269-3
Zhao Y, Seelhammer TG, Barreto EF, Wilson JW.

Altered Pharmacokinetics and Dosing of Liposomal
Amphotericin B and Isavuconazole during
Extracorporeal Membrane
Oxygenation. Pharmacotherapy. 2020;40(1):89-95.
Isavuconazole >99% ~450 L
3.5 (PubChem) doi:10.1002/phar.2348
Honore PM, De Bels D, Gutierrez LB, et al.

Optimizing micafungin dosing in critically ill
patients: what about extracorporeal therapies?. Crit
Care. 2018;22(1):289. Published 2018 Nov 1.
doi:10.1186/s13054-018-2231-6
Watt KM, Cohen-Wolkowiez M, Williams DC, et al.

Antifungal Extraction by the Extracorporeal
Membrane Oxygenation Circuit. J Extra Corpor
Technol. 2017;49(3):150-159.
Micafungin
CLSI breakpoint (candida
glabrata): 0.25 mcg/mL
albicans): 1 mcg/mL
0.39 +/-
Per Andes (2011), (-)1.6 >99%
0.11 L/kg
AUC/MIC ratio of >/= 3000 (Pubchem) (lexicomp)
López-Sánchez M, Moreno-Puigdollers I, Rubio-
López MI, Zarragoikoetxea-Jauregui I, Vicente-
Guillén R, Argente-Navarro MP. Pharmacokinetics of
Micafungin micafungin in patients treated with extracorporeal
CLSI breakpoint (candida membrane oxygenation: an observational
prospective study. Farmacocinética da micafungina
glabrata): 0.25 mcg/mL em pacientes tratados com oxigenação por
CLSI breakpoint (candida membrana extracorpórea: um estudo observacional
prospectivo. Rev Bras Ter Intensiva. 2020;32(2):277-
albicans): 1 mcg/mL 283. doi:10.5935/0103-507x.20200044
0.39 +/-
Per Andes (2011), (-)1.6 >99%
0.11 L/kg
AUC/MIC ratio of >/= 3000 (Pubchem) (lexicomp)
(lexicomp)
demonstrates highest
probability of PK-PD target
attainment for candida Jullien V, Azoulay E, Schwebel C, et al. Population
species (excluding candida pharmacokinetics of micafungin in ICU patients with
sepsis and mechanical ventilation. J Antimicrob
parapsilosis, which you can Chemother. 2017;72(1):181-189.
target 285) doi:10.1093/jac/dkw352
Mourvillier B, Jullien V, Trouillet J, et al. Increase

micafungin dose for patients under ECMO. In
Proceedings from the 27th EECMID; April 22-25,
2017; Vienna, Austria. Abstract EP0632.
Cabanilla MG, Villalobos N. A successful daptomycin

and micafungin dosing strategy in veno-venous
ECMO and continuous renal replacement [published
online ahead of print, 2021 Jul 13]. J Clin Pharm
Ther. 2021;10.1111/jcpt.13482.
doi:10.1111/jcpt.13482
Foulquier JB, Berneau P, Frérou A, et al. Liposomal

amphotericin B pharmacokinetics in a patient
treated with extracorporeal membrane
oxygenation. Med Mal Infect. 2019;49(1):69-71.
doi:10.1016/j.medmal.2018.10.011
Liposomal: In
liposome 0%; Liposomal: 0.2-
similar to 1.6 L/kg
0 deoxycholate (Stone, et al) Zhao Y, Seelhammer TG, Barreto EF, Wilson JW.
Amphotericin when released Altered Pharmacokinetics and Dosing of Liposomal
(PubChem) from liposome Deoxycholate: Amphotericin B and Isavuconazole during
2.-2.3 (Stone, Extracorporeal Membrane
Deoxycholate: et al) Oxygenation. Pharmacotherapy. 2020;40(1):89-95.
doi:10.1002/phar.2348
90% (Lexicomp)
Watt KM, Cohen-Wolkowiez M, Williams DC, et al.

Antifungal Extraction by the Extracorporeal
Membrane Oxygenation Circuit. J Extra Corpor
Technol. 2017;49(3):150-159.
Fluconazole
11-12% 0.6 L/kg
albicans): 8 mcg/mL 0.4 (Pubchem) Dhanani JA, Lipman J, Pincus J, et al.
(Lexicomp) (Lexicomp) Pharmacokinetics of fluconazole and ganciclovir as
CLSI breakpoint (candida combination antimicrobial chemotherapy on ECMO:
glabrata): 64 mcg/mL a case report. Int J Antimicrob Agents.
2021;58(5):106431.
doi:10.1016/j.ijantimicag.2021.106431
Van Daele R, Brüggemann RJ, Dreesen E, et al.
Pharmacokinetics and target attainment of
intravenous posaconazole in critically ill patients
during extracorporeal membrane oxygenation. J
Antimicrob Chemother. 2021;76(5):1234-1241.
doi:10.1093/jac/dkab012
261 L (IV)
Posaconazole >98% and 287 L
4.6 (PubChem)
(Lexicomp) (oral)
(Lexicomp
Class: Other antibiotics

Pharmacokinetics of Sulfamethoxazole and
Trimethoprim During Venovenous Extracorporeal
0.5 L/Kg Membrane Oxygenation: A Case
~70% Report. Pharmacotherapy. 2020;40(7):713-717.
0.9 (PubChem) (Dhanani, et doi:10.1002/phar.2413
(Lexicomp)
al)
Sulfamethoxazole-
trimethoprim Lopez, N; Raz, Y. 948:
Trimethoprim/sulfamethoxazole pharmacokinetics
in extracorporeal membrane oxygenation. Crit Care
1.6 L/kg
~40% Med. 2018;46(1):457. doi:
0.9 (PubChem) (Dhanani, et 10.1097/01.ccm.0000528955.49941.2b
(Lexicomp)
al)
Turner RB, Rouse S, Elbarbry F, Wanek S, Grover V,

Chang E. Azithromycin Pharmacokinetics in Adults
With Acute Respiratory Distress Syndrome
Undergoing Treatment With Extracorporeal-
7-51% 31-33 L/kg Membrane Oxygenation. Ann Pharmacother.
Azithromycin 4 (PubChem) 2016;50(1):72-73. doi:10.1177/1060028015612105
Nikolos P, Osorio J, Mohrien K, Rose C.

Pharmacokinetics of linezolid for methicillin-
resistant Staphylococcus aureus pneumonia in an
adult receiving extracorporeal membrane
oxygenation. Am J Health Syst Pharm.
2020;77(11):877-881. doi:10.1093/ajhp/zxaa066
31% 0.65 L/kg

Linezolid 0.7 (PubChem)
(Lexicomp) (Lexicomp) Kühn D, Metz C, Seiler F, et al. Antibiotic
2020;24(1):664. Published 2020 Nov 25.
doi:10.1186/s13054-020-03397-1
Mulla H, Pooboni S. Population pharmacokinetics of
vancomycin in patients receiving extracorporeal
membrane oxygenation. Br J Clin Pharmacol.
2005;60(3):265-275. doi:10.1111/j.1365-
2125.2005.02432.x
Cheng V, Abdul-Aziz MH, Burrows F, et al.

Population pharmacokinetics of vancomycin in
critically ill adult patients receiving extracorporeal
membrane oxygenation (an ASAP ECMO study)
[published online ahead of print, 2021 Oct
11]. Antimicrob Agents Chemother.
2021;AAC0137721. doi:10.1128/AAC.01377-21
Jung Y, Lee DH, Kim HS. Prospective Cohort Study of

Population Pharmacokinetics and
Pharmacodynamic Target Attainment of
Vancomycin in Adults on Extracorporeal Membrane
Oxygenation. Antimicrob Agents Chemother.
2021;65(2):e02408-20. Published 2021 Jan 20.
doi:10.1128/AAC.02408-20
Donadello K, Roberts JA, Cristallini S, et al.

Vancomycin population pharmacokinetics during
extracorporeal membrane oxygenation therapy: a
matched cohort study. Crit Care. 2014;18(6):632.
Published 2014 Nov 22. doi:10.1186/s13054-014-
0632-8
Moore JN, Healy JR, Thoma BN, et al. A Population

Pharmacokinetic Model for Vancomycin in Adult
Patients Receiving Extracorporeal Membrane
Oxygenation Therapy. CPT Pharmacometrics Syst
Pharmacol. 2016;5(9):495-502.
doi:10.1002/psp4.12112
Park SJ, Yang JH, Park HJ, et al. Trough

Concentrations of Vancomycin in Patients
Undergoing Extracorporeal Membrane
(-)2.6 ~55% 0.4-1 L/kg Oxygenation. PLoS One. 2015;10(11):e0141016.
Vancomycin Published 2015 Nov 6.
(PubChem) (Lexicomp) (Lexicomp) doi:10.1371/journal.pone.0141016
Mahmoud AA, Avedissian SN, Al-Qamari A, Bohling

T, Pham M, Scheetz MH. Pharmacokinetic
Assessment of Pre- and Post-Oxygenator
Vancomycin Concentrations in Extracorporeal
Membrane Oxygenation: A Prospective
Observational Study. Clin Pharmacokinet.
2020;59(12):1575-1587. doi:10.1007/s40262-020-
00902-1
Marella P, Roberts J, Hay K, Shekar K. Effectiveness
of Vancomycin Dosing Guided by Therapeutic Drug
Monitoring in Adult Patients Receiving
Extracorporeal Membrane Oxygenation. Antimicrob
Agents Chemother. 2020;64(9):e01179-20.
Published 2020 Aug 20. doi:10.1128/AAC.01179-20
Wu CC, Shen LJ, Hsu LF, Ko WJ, Wu FL.

Pharmacokinetics of vancomycin in adults receiving
extracorporeal membrane oxygenation. J Formos
Med Assoc. 2016;115(7):560-570.
doi:10.1016/j.jfma.2015.05.017

Therapeutic drug monitoring and adequacy of
Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
Cabanilla MG, Villalobos N. A successful daptomycin

and micafungin dosing strategy in veno-venous
0.1 L/kg, ECMO and continuous renal replacement [published
online ahead of print, 2021 Jul 13]. J Clin Pharm
0.23 L/kg in Ther. 2021;10.1111/jcpt.13482.
(-)5.1 90-93%
Daptomycin critically ill doi:10.1111/jcpt.13482
(DrugBank) (Lexicomp)
adults
(Lexicomp)
Class: Quinolones
Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
(-)1.1 20-40% 2.1-2.7 L/kg

Ciprofloxacin
(PubChem) (Lexicomp) (Lexicomp) Sinnah F, Shekar K, Abdul-Aziz MH, et al.
Incremental research approach to describing the
pharmacokinetics of ciprofloxacin during
extracorporeal membrane oxygenation. Crit Care
Resusc. 2017;19(Suppl 1):8-14.
(-)0.4 ~24-38% 1.27 L/kg
Levofloxacin
(PubChem) (Lexicomp) (Lexicomp)
~30-50% 1.7-2.7 L/kg

Moxifloxacin 0.6 (PubChem)
Class: Aminoglycosides
Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
(-)4.1 <30% 0.2-0.3 L/kg

Gentamicin

Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
(-)6.2 <30% 0.2-0.3 L/kg

Tobramycin
Ruiz-Ramos J, Gimeno R, Pérez F, et al.

Pharmacokinetics of Amikacin in Critical Care
Patients on Extracorporeal Device. ASAIO J.
2018;64(5):686-688.
doi:10.1097/MAT.0000000000000689
(-)7.9 0-11% 0.25 L/kg

Amikacin
Touchard C, Aubry A, Eloy P, et al. Predictors of
insufficient peak amikacin concentration in critically
ill patients on extracorporeal membrane
oxygenation. Crit Care. 2018;22(1):199. Published
2018 Aug 19. doi:10.1186/s13054-018-2122-x
(-)7.9 0-11% 0.25 L/kg

Amikacin
Gélisse E, Neuville M, de Montmollin E, et al.
Extracorporeal membrane oxygenation (ECMO)
does not impact on amikacin pharmacokinetics: a
case-control study. Intensive Care Med.
2016;42(5):946-948. doi:10.1007/s00134-016-4267-
x

Med. 2019;38(5):493-497.
doi:10.1016/j.accpm.2019.02.015
Class: Antivirals
Mulla H, Peek GJ, Harvey C, Westrope C, Kidy Z,
Ramaiah R. Oseltamivir pharmacokinetics in
critically ill adults receiving extracorporeal
membrane oxygenation support. Anaesth Intensive
Care. 2013;41(1):66-73.
doi:10.1177/0310057X1304100112
23 to 26 L;
May be Eyler RF, Heung M, Pleva M, et al. Pharmacokinetics
significantly of oseltamivir and oseltamivir carboxylate in
42% increased in critically ill patients receiving continuous
venovenous hemodialysis and/or extracorporeal
(prodrug) patients membrane oxygenation. Pharmacotherapy.
Oseltamavir 1.1 (PubChem) 3% (active receiving 2012;32(12):1061-1069. doi:10.1002/phar.1151
compound) ECMO
(Lexicomp) (Lemaitre
2012; Mulla
2013)
(Lexicomp)
(prodrug) patients
Oseltamavir 1.1 (PubChem) 3% (active receiving
compound) ECMO
(Lexicomp) (Lemaitre
2012; Mulla
2013)
(Lexicomp) Lemaitre F, Luyt CE, Roullet-Renoleau F, et al.
Impact of extracorporeal membrane oxygenation
and continuous venovenous hemodiafiltration on
the pharmacokinetics of oseltamivir carboxylate in
critically ill patients with pandemic (H1N1)
influenza. Ther Drug Monit. 2012;34(2):171-175.
doi:10.1097/FTD.0b013e318248672c

Pharmacokinetics of fluconazole and ganciclovir as
combination antimicrobial chemotherapy on ECMO:
a case report. Int J Antimicrob Agents.
0.74 +/- 2021;58(5):106431.
(-)2.5 1-2%
Ganciclovir 0.15 L/kg doi:10.1016/j.ijantimicag.2021.106431
(PubChem) (Lexicomp)
(Lexicomp)
Class: Opioids
Fentanyl
Hydromorphone
Morphine
Class: Sedatives
Propofol
Dexmedetomidine
Midazolam
Lorazepam
Other (miscellaneous)
Quetiapine 2.1 (PubChem) 83% 10 +/- 4 L/kg
Amiodarone
Study summary
A pharmacokinetic study of two adult patients (VV and VA ECMO) in which bound and unbound ceftriaxone levels were
measured at 0.5, 1, 2, 6 and 12 after dosing demonstrated adequate unbound ceftriaxone trough levels to achieve
100%fT>MIC and 100%fT>4xMIC. Of note, the patient receiving CNS dosing may not have met PK/PD target with q24hour
dosing due to augmented renal clearance.
- Patient 1 (61 yo M): VV ECMO, ceftriaxone 2 g q12hours
- Patient 2 (51 yo W): VA ECMO, ceftriaxone 2g q24hours
Protocol only, no results

- looking at ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactam, ticarcillin-clavulanate,
linezolid, fluconazole, voriconazole, caspofungin, oseltamavir, midazolam, morphine, fentanyl, propofol, dexmedetomidine,
thiopentene
- Population PK and monte-carlo simulations to develop dosing recommendations in ECMO
No studies available
Need to request from interlibrary loan
PK study of 6 patients receiving VA ECMO and cefazolin 6g/24 hour administered as continuous infusion with target defined
as unbound steady stata concentration of 4x-8x ECOFF (2 mg/L unbound concentration of cefazolin).
- 4/6 patients (11/17 samples) on concurrent CRRT.
- 1/17 samples did not meet 4x ECOFF target, 4/17 were 4x-8x ECOFF, 12/17 were >8x ECOFF
- Clearance was increased in patients NOT requiring renal replacement therapy (8.5
L/h ± 3.8 L/h s.d. vs. 2 L/h ± 0.4 L/h s.d.)
TDM from 27 patients on VA or VV ECMO (14/27 on RRT) for piperacillin-tazobactam were used for PK modeling and MC
simulation to determine PTA for 50% T>MIC16 and 100% T>MIC16 at CrCl 30 ml/min, 100 ml/min and 160 ml/min. Initially
intended to find PTA toxicity based on Cmin>360 mg/ml, but incidence in the cohort was <3%. The PTA for CrCl 100 ml/min:
- PTA 50% T>MIC for 4.5g q8hr over 4 hours = ~95%; PTA 100% T?MIC for 4.5g q8hr over 4 hours = ~35%
- PTA 50% T>MIC for 4.5gq6hr over 4 hours = 100%; PTA 100% T>MIC for 4.5g q6hr over 4 hours = 55%
Also evaluated PTA for tazobactam for 100% fT>CT=2mg/L
- PTA 95-97% for 4.5g q6hr over 4 hours; PTA ~90% for 4.5g q8hr over 4 hours)
SEE FIGURE TO RIGHT
A matched cohort study of 14 pairs of patients receiving VA/VV ECMO (intervention) or no ECMO (control) compared 2
hours after the start of the 30-minute infusion and immediately prior to subsequent dosing of piperacillin-tazobactam.
Adequate concentration was defined as T>4x MIC (using EUCAST pseudomonas breakpoints) of at least 50% the dosing
interval.
- Found no difference in attaining adequate concentrations of piperacillin-tazobactam in ECMO patients versus non-ECMO
controls (no statistics provided, graph only)
- Piperacillin dosing for a patient with normal renal function was 4 g q6hr)
- inluded matched pairs who were receiving CVVH (N=9 between both groups)
A study of 27 patients receiving VA or VV ECMO defined population pharmacokinetics for piperacillin-tazobactam and
evaluated probability of target attainment, defined as either 50% T>MIC or 100% T>MIC.
- 51% of patients received concomittant CVVHDF or CVVHD
-For all patients (irrespective of renal function), probability of target attainment was highest for the group receiving 4.5 g
piperacillin-tazobactam every 6 hours via extended infusion (both 50% T>MIC and 100% T>MIC)
- For 100% T>MIC, target attainment with piperacillin-tazobactam dosed at 4.5 g q6hr was low -- ~0.55 and ~0.35 for
patients with CrCl 100 ml/min and 160 ml/min respectively
- For 50% T>MIC, target attainment was 1.0 for patients with CrCl 30 ml/min, 100 ml/min and 160 ml/min
- probability of toxicity (defined as Cmin >360 mg/L) was highest (~0.35) for 4g piperacillin q6hr dosing regimens, followed by
q8hr dosing regimens (~0.25), followed by q12hr dosing regimen (0.1)
Proportion of time above 4x the MIC for pseudomonas aeruginosa (>/= 64 mg/L) was compared for patients receiving
piperacillin-tazobactam 4.5 g every 6 hours via extended infusion (4.5 g q8 hr if CrCl 20-40, 4.5 g q12hr if CrCl < 20) in
patients receiving either VA or VV ECMO (n=21) and matched controls (n=21). Patients requiring renal replacement therapy
were excluded.
- First dose: proportion of dosing interval >/= 64 mg/L was 0.56 (IQR 0.43-0.71) in ECMO patients compared to 0.56 (IQR
0.43-0.71) in non-ECMO controls
- Steady state: proportion of dosing interval >/= 64 mg/L was 1.0 (IQRR 0.8-1.0) in ECMO patients compared to 0.96 9IQR
0.55-1.0) in non-ECMO controls
19 patients on VA or VV ECMO received piiperacillin-tazobactam at various doses and intervals (median 4.5 g q6 hours via
extended infusion). PK goals were based on the MIC for pseudomonas (EUCAST) and were defined as 4x MIC at 50% of
dosing interval and Cmin>MIC at 100% dosing interval. 68.7% of patients acheived 4x MIC at 50% dosing interval and 93.7%
had a concentration greater than the MIC for pseudomonas at 100% of the dosing interval.
- 41% of all patients in the study (which included patients receiving different antibiotics) received concurrent CRRT; median
CrCl for all patients was 20 ml/min (IQR 10-69)
TDM performed on 14 patients on VA/VV ECMO on continuous infusion piperacillin-tazobactam. Target was defined as SS
level >4x MIC for enterobacterales (target 32 mcg/mL)
- Dosing: 4.5g loading dose followed by 13.5g/24 hours for CrCl>/=30 ml/min or 9g/24hr if CrCl<30 ml/min or 13.5g/24hr in
CRRT
- Median serum concentration: 32.3 mcg/mL (26.7-55.9), N=14 patients, 31 measurements
- 53% patietns on CVVH (in all abx groups)
Case report of a patient with MSSA bioprosthetic valve endocarditis on VA ECMO who received oxacillin 2 g over 30 minutes
q4hr. The patient had normal renal function (CrCl > 60 ml/min) Steady state post-distribution level was drawn 28 minutes
after completion of infusion on D4 of therapy, and trough level was drawn 29 minutes prior to the next dose.
- post distribution level: 82.2 mg/L (estimated Cmax unbound: 8.33 mg/L)
- trough level: 2.93 mg/L (estimated Cmin unbound: 0.089 mg/L)
- estimated %T>MIC = 58% of dosing interval
10 patients on VA or VV ECMO received imipenem-cilastatin at various doses and intervals (median 1g q8hr). PK goals were
based on the MIC of pseudomonas (EUCAST). Target attainment was defined as achieving 4x MIC at 50% of the dosing
interval and Cmin>MIC at 100% of the dosing interval. 4x MIC was acheived in only 1 out of 10 patients and Cmin>MIC was
acheived in only 4 of 10 patients.
Study defines population PK for 247 patients receiving imipenem-cilastatin, including 48 patients in ECMO. Target
attainment was based on 40% and 70% T>MIC for patients on ECMO. Monte Carlo simulations found PTA was lower for
patients receiving ECMO than for non-ECMO patients. PTA (40% T>MIC and 70% T>MIC) for different dosing regimens and
MICs in ECMO:
- 750 mg q6hr: PTA 81.5% for MIC = 2 mcg/mL; 50.6% for MIC = 4 mcg/mL --> for 70% T>MIC
** Difficult to interpret MC sims for other dosing regimens because no labels for different dosage regimens on figure (see
left), also supplement not helpful and presents only PTA for different covariates but not ECMO; also many patients were on
CRRT too; did not specify duration of infusion. Rate this as low quality of evidence **
Study pools data from 50 patients from previous studies and unpublished data to determine population PK of patients
receiving ECMO and imipenem-cilastatin at various dosage regimens and sites of infection. MC simulations were performed
and PTA was calculated based on achieving 40% T>MIC and 75% T>MIC for the different dosing regimens (all based on
MIC=2 mcg/mL and CrCl 60-120 ml/min).
PTA for 40% T>MIC:
- 500 mg q8hr (4-hr infusion): 97.1%
- 1000 mg q8hr (4-hr infusion) 97.2%
PTA for 75% T>MIC:
- 500 mg q8hr (4-hr infusion): 92.7%
- 1000 mg q8hr (4-hr infusion): 91%
A matched cohort study of 27 pairs of patients receiving VA/VV ECMO (intervention) or no ECMO (control) compared 2
hours after the start of the 30-minute infusion and immediately prior to subsequent dosing of meropenem. Adequate
concentration was defined as T>4x MIC (using EUCAST pseudomonas breakpoints) of at least 40% the dosing interval.
- Meropenem dosing in study: 1g q8hr for CrCl>80, 1g q21hr for CrCl 51-81, 0.5g q12hr for CrCl 10-50, 0.5g q24hr for CrCl
<10, 1g q8hr for CRRT
- Most patients had adequate or excessive concentrations of meropenem in both the ECMO and control groups (graph only,
no statistics provided)
- Most patients were NOT receiving CRRT
Study including 10 patients to determine population PK and PTA for meropenem dosing regimens (1g q8hr over 5 minutes,
or 2g q8hr over 5 minutes). Will not include because all but one patient were on concurrent CVVH.
A population PK model of patients on ECMO with and without renal replacement were defined from a sample of 11 patients
receiving various dosage regimens of meropenem. A MC simulation was performed to determine PTA for susceptible
(pseudomonas MIC 2 mg/mL) and less susceptible (pseudomonas MIC = 8 mg/mL) for five differenct CrCl.
Dosage regimens in MC sim (CrCl 80, 120):
(MTC=mean trough concentration, 10th=10th percentile trough concentration)
- 0.5g q8hr: MTC=10 mcg/ml, 7.6 mcg/ml; 10th=1.3 mcg/ml, 0.7 mcg/ml
- 1g q8hr: MTC=14.8 mcg/ml, 11.1 mcg/ml; 10th=4.8 mcg/ml, 2.5 mcg/ml
- 2g q8hr: MTC=39.7 mcg/mL, 30.0 mcg/mL; 10th=5.1 mch/ml, 2.7 mcg/ml
** see full table to left for 10th percentile and mean trough concentrations for other CrCl
TDM performed on 18 patients on VA/VV ECMO on continuous infusion meropenem. Target was defined as SS level >4x MIC
for enterobacterales (target 8 mg/ml)
- Standard dosing: 2 g LD, followed by 3g/24hr (for all CrCl and CVVH)
- High dose: 2g LD, follwed by 6g/24hr if CrCl>/=30ml/min, 3g/24hr if CrCl<30 ml/min, 6g/24hr on CVVH
- Median serum concentration STANDARD dosing: 15.5 mcg/ml (11.8-22.2), N=12, 33 measurements
- Median serum concentration HIGH dose: 16.9 mcg/ml (13.7-32.9_, N=6, 16 measurements
12 patients on VA or VV ECMO received cefotaxime at various doses and intervals (median 7 g per day). Target attainment
was defined as achieving 4x MIC for enterobacteriacea (4 mg/L) at 50% of the dosing interval and Cmin>MIC (1 mg/mL( at
100% of the dosing interval. 4x MIC at 50% dosing interval was acheived in 100% of patients and Cmin>MIC was acheived in
81.8% of patients.
TDM performed on 7 patients on VA/VV ECMO on continuous infusion ceftazidime. Target was defined as SS level >4x MIC
for enterobacterales (target 16 mcg/mL)
- Dosing: 2g LD followed by 6g/24hr if CrCl>/=30 ml.min, 4g/24hr if CrCl<30 ml/min, 6g/24hr if CVVH
- median serum concentration: 49.3 (42.0-69.0), N=7, 9 measurements
Case report of a patient with invasive pulmonary and cerebral aspergillosis started on voriconazole at dose of 400 mg q12hr
x2 doses for loading, then 280 mg q12hr prior to initiation of ECMO. At time of ECMO cannulation, voriconazole dosing was
increased empirically to 400 mg q12hr to compensate for increased volume of distribution and sequestration. Prior to
initiation of ECMO, steady state trough levels were 7.07 and 7.34 mcg/ml. Following initiation of ECMO therapy, trough
levels were 7.34, 7.45, 10.55 and 13.28 on ECMO days 1, 2, 3 and 4 respectively.
- Patient was CYP2C19 wild type (not poor metabolizer)
- Patient had an increase in mean tbili during ECMO (6.94 mg/dL) compared to pre-ECMO mean tbili (3.36 mg/dL)
Case report demonstrating blood levels of voriconazole were reduced for a patient receiving VA ECMO and voriconazole at a
dose of 400 mg BID (patient weight = 50 kg).
- table showing trough levels is unclear. States trough level was drawn 24 hours after previous dose, even though body of
text states that dosing was q12hr. In "dose" column, states that dose was 400 mg x2, not sure what this means.
- Trough on D7 of voriconazole treatment was 0.5 mg/L, on D8 trough waws undetectable
Case report of 26 year old male with invasive blastomycosis on VA ECMO. Due to high fungal burden despite dose
escalations of liposomal amphotericin and concern for reduced bioavailability and drug interactions with posaconasole and
itraconazole, isavuconazole was added on ECMO day 64 at a dose of 372 mg once daily. Goal Cmin of >3 mcg/mL was
defined by the treatment team prior to starting therapy. On ECMO day 74, isavuconazole dose was increased to 372 mg
q12hr due to trough level of 1.9 mcg/ml. Subsequent isavoconazole trough levels were 4.1 mcg/ml on ECMO day 86 and 4.7
on ECMO day 168.
Editorial cites Watt, et al. and Mourvilliers, et al. and states that higher doses of micafungin (200 mg q24hr) are
recommended for patients receiving ECMO, especially when on concomittant CVVH or with more resistant candida strains.
Ex vivo study (don't include)

Results show that micafungin undergoes considerable extraction by the circuit, and extraction increases when a hemofilter is
present (46% at 4 hours when hemofilter in line vs 91% when hemofilter NOT in line). At 24 hours, recovery was 26% when
hemofilter was present and 43% when hemofilter was NOT present compared to 57% recovered in control. (not sure what
the application of the data with hemofilter present is, because I don't think we have this in our circuits - would just be on
separate CVVH circuit)
Observational, prospective study of 12 patients on VA or VV ECMO did not demonstrate any significant differences in the
pre- and post-membrane concentrations on D1 and D4 of micafungin therapy. Also found no significant difference between
pre- and post-membrane Cmax, Cmin, AUC, Vd and Cl on either D1 or D4.
- AUC pre-/post-membrane on D1: 54.9 mcg/mL & 54.1 mcg/mL
- AUC pre-/post-membrane on D4: 88.8 mcg/mL & 81.0 mcg/mL
Population PK study which evaluated effect of ECMO as a covariate on PK parameters in critically ill patients. ECMO was NOT
found to have an effect on Vd or Cl of micafungin.
Cohort study comparing first dose PK for micafungin 100 mg in patients on ECMO compared to matched controls. Found a
median AUC of 101.2 [65.4-116.1] in controls compared to 74.7 [56.5-80.6] in ECMO patients. When adjusted for weighe,
albumin level and SOFA score, there wsa found to be a 23% reduction in AUC in patients receiving ECMO compared to
matched controls (p=0.29)
Evalutates a single patient receiving VV-ECMO and CVVH, will not include
Case report describes PK of a single patient who received LAmB for invasive aspergillosis receiving VV ECMO. They described
decreased Cmax concentrations compared to critically ill non-ECMO patients. Of note, extended infusion of LAmB was used,
which may have decreased the Cmax for this patient.
Case report of a 26 year old man who received LAmB for a LAmB-susceptible blastomycosis. Prior to VA ECMO cannulation
he was treated with 5 mg/kg/day, following cannulation the dose was empirically increased to 7.5 mg/kg/day. During the
course of his illness, a second circuit was added to augment R ventricular function and oxygenation. Due to lack of clinical
improvement, the dose of LAmB was increased to 10 mg/kg/day and isavuconazole was added to augment antifungal
therapy. TDM was performed at the 10 mg/kg/day dose with target Cmax of 83 μg/ml or greater and Cmax/MIC greater
than 40. The patient's Cmax at steady state was 92.5 mcg/mL. The patient was also receiving CVVH.
Ex vivo study (don't include)

Shows that fluconazole is minimally extracted by the circuit with 95-98% of drug recovered after 24 hours compared to
101% in control.
Case report, 33-yo male with newly diagnosed HIV, normal renal function, receiving fluconazole 6 mg/kg/day for prophylaxis
Multicenter study evaluates PTA for posaconazole in 6 patients with influenza on VV ECMO who received prophylactic
posaconazole dosing for aspergillosis. Patients received IV posaconazole 300 mg q12hr for 2 doses, followed by 300 mg q24
hours for maintenance.
- 2 patients on concommitant CVVH
- PK modeling demonstrated larger Vd in ECMO patients compared to published parameters for non-ECMO patients (389 L)
- Based on a goal trough level of 0.7 mg/mL for prophylaxis and a goal trough level for treatment; PTA >90% was
demonstrated for prophylaxis but not for treatment
- Despite PTA <90% for treatment, the AUC0-24 was greater than 22.5, indicating therapeutic levels for susceptible
aspergillus sp (based on EUCAST breakpoint of 0.125 for aspergillus sp)
Case report of a 33 year old male patient with AIDS, PJP pneumonia and normal renal function who received
sulfamethoxazole-trimethoprim 20 mg TMP/kg/day in 4 divided doses while undergoing VV-ECMO for respiratory failure.
Serum concentrations of both TMP and SMX were measured 1, 2, 4, 8 and 12 hours after administration at steady state.
From the patient's data, Cmax and Cmin were reported. They also reported pre- and postoxygenator Cmax, Cmin and AUC0-
6.
- sulfa Cmax=122 mcg/mL
- extraction ratio for SMX & TMP based on pre- and postoxygenator levels= 0.02, 0.05
Case series of two patients receiving TMP-SMX for treatment of stenotrophomonas maltophilia and PJP received 20 mg
TMP/kg/day in 4 divided doses.
- Steno case: initially used 15 mg/kg/day, but increased to 20 mg/kg/day with persistently positive culture on ECMO day 7.
Cmax was 229.8 mcg/ml
- PJP case: Cmax was 135.5 mcg/ml
PK data was obtained from 3 patients receiving VV ECMO support and azithromycin at a dose of 500 mg q24hr. The
calculated AUC, Cmin and Cmax were compared to those of non-ECMO patients and not found to be significantly different.
An interesting finding is that azithromycin exhibited a smaller volume of distribution for patients on ECMO compared to non-
ECMO patients (19.8 L/kg vs 33.3 L/kg)
Case report of a 55 year old male patient who underwent VV ECMO support following lung transplant complicated by MRSA
pneumonia. Due to inability to obtain target vancomycin trough concentrations, the patient was switched to linezolid 600
mg q8hr. TDM was performed with a target Cmin of >/= 2 mcg/ml and AUC:MIC >80. On day 6 of linezolid therapy, serum
peak and trough levels were obtained and an extrapolated true trough and 24 hour AUC were calculated. The Cmin was 0.35
and the 24 hour AUC was 21.6 mch*hr/L which resulted in an AUC:MIC of 10.8 for an MRSA isolate with an MIC of 2
mcg/ml. Subsequently, the patient was switched from linezolid to ceftaroline for treatment of his MRSA pneumonia.
Case control study of patients receiving ECMO support (N=9) and non-ECMO controls (N=1) and continuous infusion linezolid
at a dose of 1800 mg/day found no significant difference in steady state serum levels between the two groups. Despite this
non-significant finding, there was still a large proportion of patients (35%) who failed to achieve sufficient concentration
targets to meet the predefined goal Css of 6.5-12 (1.6-3x EUCAST MIC breakpoint of 4 mg/dL)
Population PK study of 45 adult, pediatric and neonatal patients (including both prospective and retrospective data) created
a two-compartment PK model expressing clearance based on age, and serum creatinine as covariates; Vd and half-life. For
the adult patients, V1 was 0.37 L/kg, Vss was 0.73 L/kg and the half life was 8.55 hr. Compared to non-ECMO PK from
lexicomp, Vd is similar and clearance is increased (4-6 hr).
Population PK study of 22 adult patients on VA and VV ECMO who received vancomycin via intermittent infusion, 11 patients
received concomittant RRT (CVVHDF, CVVHD, EDD, SLED). The two-compartment model describing the data included TBW,
Vc and CrCl as covariates. Overalll clearance (RRT and non-RRT) was found to be 3.2 L/hr, Vc was 29.73 L. The invesitgators
compared their model to previously published PK models for ECMO patient receiving vancomycind and did not find any large
differences in Vc or Cl.
Population PK study of 22 adult patients on VA and VV ECMO obtained serum vancomycin measurements after a single 1000
mg dose. Investigators derived a three-compartment PK model to describe Cl and Vss in ECMO patients.
- Cl = 4.01 L/hr
- V1 = 8.01 L
Findings were similar to previously published population PK studies for both ECMO and non-ECMO patients.
Case control PK study of 11 ECMO patients and 11 matched controls to decribe Vd and Cl of vancomycin. Patients received
vancomycin as a continuous infusion. Serum vancomycin measurements were obtained during the first 24 hours of ECMO
support (excluded patients receiving vancomycin prior to ECMO cannulation). 7 patients underwent concomittant RRT.
Dosing regimen: 35 mg/kg LD followed by dosing sufficient to obtain serum concentrations between 20-30 mcg/mL, inital
dosing based on CrCl. Investigators found a non-significatn decrease in vancomycin Cl in ECMO patients compared to non-
ECMO patients, and a non-significant DECREASE in Vc between ECMO and non-ECMO patients (based on a two-
compartment model)
- Vd 99.3 L (bootstrap from model Vc = 31.8 L)
- Cl 2.4 L/hr (bootstrap from model = 3.7 L/hr)
Population PK study of 14 patients on VA and VV ECMO describes a two-compartment model to determine vancomycin Cl
and Vc. 0 patients received concomittant RRT. Vc was 24.2 L and Cl was 2.83 L/hr. These estimates were similar to previously
published PK studies.
Will not include. Looked at specific dosing regimen (1g load, followed by 1g q12) and found that trough levels were
inadequate. Don't think this applies to our population since we use much more aggressive dosing.
Population PK study used 3-compartment model using CrCl, ,TBW and ECMO flow rate as covariates to describe Cl and V1 for
vancomycin in 11 patients undergoing VA ECMO. Also compared pre- and post-oxygenator concentrations of vancomycin to
evaluate % of drug sequestered in the oxygenator.
- found small decreases in post-oxygenator concentrations at 6, 12, 18 and 24 hours post-dosing
- V0 = 13.4 L
- Cl = 6.89
Found similar V0 and Cl compared to previously discussed population PK studies.

Retrospective study evaluates attainment of therapeutic vancomycin trough concentrations in patients undergoing VA and
VV ECMO support. 33.3% of patients in the cohort received concomittant RRT. They found lower proportion of patients with
vancomycin trough concentrations in the therapeutic range early in therapY (<6 days) compared to late therapy (6-13 days)
suggesting that there is a higher likelihood in overestimating AND underestimating vancomycin dosing requirements early
on in therapy in patients receiving ECMO support.
- target trough level 15-20 mcg/mL
- proportion of patients with supratherapeutic, therapeutic and subtherapeutic trough concentrations were 46%, 24% and
30% respectively.
- higher proportion of supratherapeutic levels in patients with RRT (no details about mode of RRT or dosing strategy in these
patients, so not sure how much meaning can be gleaned from this finding in our patients at UW.
- Did not compare to proportion of therapeutic vancomcyin trough requirements in non-ECMO patients at this institution, so
hard to know if this is due to ECMO or imprecision of initial dosing recommendations for vancomycin.
- Dosing strategy: 25 mg/kg loading dose, followed by 15 mg/kg q12hr. Trough levels were drawn before 4th maintenance
dose. Dosing strategy for patients with renal dysfunction or RRT not included.
Matched cohort study of 11 ECMO patients and matched controls (age, gender, CrCl) evaluated vancomycin levels at steady
state. Levels were drawn 0.5, 1, 2, 3, 7, 11, 23, 35 & 47 hours post infusion. Population PK estimates for half-life, CL and Vss
were derived froom the patient-level data. There were no significant differences in PK parameters bewtween the ECMO
group and their matched controls.
- CL = 1.18 ml/min/kg (~5 L/hr for 70 kg patient)
- Vss = 0.84 K/kg
There was found to be a significant decrease in clearance when comparing the roller pump group to their matched controls,
but roller pumps are not as commonly used and not a part of the ECMO circuit at UW Health.
THIS STUDY IS NOT VERY GOOD FOR VANCO, considering excluding

Prospective observational study evaluated target attainment as defined as a steady state plasma concentration of 50-30
mg/L. Does not specify whether this was a trough level. 5 patients were included with a dosing regimen of vancomycin
2g/day. MIC is listed as 4 (doesn't specify which organism, assuming MRSA?), but this seems really high given target
AUC:MIC 400-600 would need toxic concentrations to meet PK goal. states 80% of drug concentrations measured were
"adequate"
evaluates a single patient on VV ECMO and CVVH, will not inlcude
Two patients received ciprofloxacin 800 mg per day and had "adequate" serum concentrations, however this is not defined.
Will not include
Presenting data from ovine model, but validate using data from a critically ill male patient undergoing VA ECMO. This
patient received cipro 400 mg q8hr. Blood samples collected 0, 15, 30, 45, 60, 90, 120, 180 and 480 minutes following cipro
infusion. PK parameter estimates for the human patient were Cl 0.15 L/kg/h, Vd 0.99 L/k - similar to population PK estimates
in other critically ill patients. Ciprofloxacin PK does not appear to be significantly altered in the setting of ECMO.
Single patient treated with gentamicin dosed at 11.1 mg/kg attained a Cmax of 38.2 mg/L (goal 30-40). Same limitations of
this study as listed for Amikacin.
Single patient treated with tobramycin dosed at 7.1 mg/kg attained Cmax 13.7, state this is below the target concentration
(don't provide what they were targeting, seems like this is pretty high considering we target 8-10 mg/l for CNS indications
for susceptible organisms. Possibly goal for extended interval dosing? Same limitations of this study as listed for Amikacin.
Prospective, observational study evaluated the Cmax and Cmin of 9 patients undergoing VA or VV ECMO support and
compared them to non-ECMO controls (1 ECMO:1 critically ill:1 CVVH). Average dose administered was 14 mg/kg. Average
Cmax in the ECMO group was 52.2 mg/L compared to 52.6 mg/L in the non-ECMO, non-CVVH control group. 24-hour Cmin
averaged 6.6 mg/L in the ECMO group compared to 5.02 mg/L in the non-ECMO, non-CVVH group.. CL in L/hr/kg was similar
between the ECMO group and non-ECMO, non-CVVH controls (0.040 vs 0.041); however the L/hr Cl was lower in the ECMO
group (3.73 vs 1.581).
Vd was also compared between the ECMO group and non-ECMO, non-CVVH controls:
- Vd = 0.346 L/kg vs 0.288 L/kg
prospective, observational study evaluated Cmax and Cmin of 106 patients undergoing VA or VV ECMO support after the
first dose 25 mg/kg of amikacin. Collected extensive baseline info to be able to correlate patient-specific factors with
likelihood of acheiving insufficient amikacin peak concentrations (<60 mg/L)
- Median Cmax 65.8 mg/L; 39% of patients failed to acheive target peak of >60 mg/L
- Proportion of patients with Cmax>80 was 25%
- Median Cmin (defined as 24 hours post-dose) was 7.25 mg/L; 28% of patients had Cmin<2.5 at 24 hours
- Vd was not reported
- Low BMI, elevated LFTs, lower hematocrit, lower total protein and positive 24-hr fluid balance were found to be associated
with failure to acheive Cmax >60 mg/L
- Higher BMI, ECMO flow, dialysis, higher hematocrit were found to be associated with Cmax > 80 mg/L (after controlled for
24-hour fluid balance, only larger BMI was associated with Cmax>80 mg/L)
- Based on population PK data, performed simulations and found that increasing dose to 30 mg/kg when 24-hour fluid
balance is positive increased the proportion of patients who acheived target peak concentrations
Case control study of 50 patients undergoing VA or VV ECMO support and matched non-ECMO controls compared peak and
trough amikacin levels after a single 25 mg/kg dose. Target peak level of amikacin was 60 mg/l. 44% of patients in the ECMO
group required renal replacement therapy. There was not found to be a significantly different Cmax between the ECMO and
non-ECMO groups (71.7 mg/L vs 68.4 mg/L). The proportion of insufficient (defined as a Cmax < 60 mg/L) Cmax
concentrations was numerically, but not statistically significantly lower in the ECMO group (26% vs 34%), however still
represented a large proportion of patients at risk of therapy failure.
- proportion of adequate Cmax (60-80 mg/L): 50% in ECMO group compared to 36% in control
- proportion of toxic Cmin (>/5 mg/L): 65% in ECMO group compared to 60% om control; these were 24 hour levels -- LARGE
proportion, but just may indicate that most patients require >24 hour dosing which is not surprising given the large
proportion of patients in this study who required RRT and the dosing regimen which is higher than standard dosing.
Evaluated attainment of Cmax 60-80 mg/L after amikacin administration in 6 patients on VA or VV ECMO. No details are
provided about the dosing regimen used, however in the conclusion the authors state "amikacin at 20 to 25 mg/kg [does]
not achieve the pk targets reported in the literature" so presuming that is what they studies. Also unclear if this was at
steady state or after a single dose. Attainment of Cmax 60-80 mg/L occurred in 4 of the 6 patients.
Prospective observational PK study of 14 patients on VV ECMO received 75 mg oselatamivir BID enterally. Blood samples
were collected pre-dose and 30, 60, 120, 240, 300, 420, 560 and 720 minutes post-dose. Samples were analyzed for both
oseltamivir (prodrug) and oselatamivir carboxylate (active compound) Samples were taken on day 1 and 5 of therapy. 4
patients received concomittant CVVH and 2 were withdrawn early due to ECMO decannulation. Population PK estimates
were compared to those of ambulatory adults.
- Vd of oseltamivir carboxylate was found to be much greater in patients on ECMO (179 vs 26 L).
- Cmin of oseltamivir carboxylate were 1000-4000 times the IC50 for H1N1, so decrease in efficacy of this dosing regimen is
unlikely despite the large difference in Vd.
Not including, PK parameters for patient who recived only ECMO were not reported
Prospective observational PK study of 7 patients on VV ECMO for H1N1 ARDS. Patients received 75 mg BID or 150 mg BID of
enteral oseltamivir. 3 patients required concomittant CVVH. Plasma samples were collected and evaluated for oseltamivir
carboxylate concentrations prior to dose administration and at 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours after administration. PK
parameters for the 4 patients who received ECMO alone were presented:
- Cmax = 1029 (range 349-1470); Cmax/D (ng/mL*mg) = 5.3 (2.3-9.8)
- AUC0-12 = 9.00 (2.2-14.5); AUC0-12/D = 0.044 (0.021-0.093
- population PK estimates were not provided, but patient level data were presented and ranged 47.2-184.4 L
Case report of a 33 year old male patient with HIV/AIDS on VV ECMO for respiratory failure. He received ganciclovir. Pre- and
postoxygenator in addition to perphieral blood samples were collected at 0, 1, 2, 4, 8 and 12 hours post-dosing and patient
specific PK parameters were calculated.
- Vz = 2.72 L/kg
- AUC0-24 = 25.39
AUC0-24 is less than proposed target for CMV treatment. Target not well defined and only single patient data so cannot
make dosage adjustment recommendations based on this - hypothesis generating
Quality of Evidence Recommendation (with SOR) UWHC dosing recommendation
Low
Ceftriaxone dosing based on clinical

indication, no dosage adjustments
recommended in setting of ECMO
(Conditional)
N/A
Cefepime dosing based on clinical

N/A
(Conditional)
Cefazolin dosing based on clinical

(Conditional)
Low
Moderate
Moderate
CrCl > 20 ml/min: Piperacillin-

tazobactam 4.5 g every 6 hours via
extended infusion
CrCl < 20 ml/min: Piperacillin-
extended infusion
(Strong)
CrCl > 20 ml/min: Piperacillin-
N/A (included 2x), extended infusion
same as Cheng study CrCl < 20 ml/min: Piperacillin-
prior to print tazobactam 4.5 g every 12 hours via
extended infusion
(Strong)
** Could consider continuous

infusion, but we don't really do that
here **
Moderate
Moderate
Moderate
Oxacillin dosing based on clinical

indication and severity of infection.
Low
No dosage adjustments
Low
Imipenem-Cilastatin dosing based on

Low clinical indication and severity of
infection. No dosage adjustments
recommended in the setting of ECMO
(Conditional)
clinical indication and severity of
infection. No dosage adjustments
(Conditional)
Moderate
Low
CrCl < 20 or iHD: meropenem dose

N/A based on GN guideline (no
recommendation
CrCl 20-50: meropenem 500 mg q8hr
via extended infusion
CrCl > 50 ml/min: meropenem 1 g
q8hr via extended infusion
For MIC > 2 mcg/mL, consider more
aggressive dosing regimens
(Strong)
High vs Moderate ** recommendation based on

attaining trough concentration > MIC
of 2 mcg/mL to target 100% T>MIC
Moderate
(not included in
recommendation because
similar TDD and don't do
continuous infusions here)
Cefotaxime dosing based on clinical

Low No dosage adjustments
recommended in setting of ECMO.
(Conditional)
Ceftazidime dosing based on clinical
Moderate indication and severity of infection.
(not included in No dosage adjustments
recommendation because don't
do CI ceftazidime here) recommended in setting of ECMO.
(Conditional)
Ceftaroline dosing based on clinical

(Conditional)
Low
Voriconazole dosing based on clinical
indication, dose adjustments based on
steady state trough concentrations.
(Conditional)
Low
Isavuconazole dosing based on clinical

indication. No dosage adjustment
Low
(Conditional)
Low
Low
Micafungin dosing based on clinical

indication. No dosage adjustments
Low
Micafungin dosing based on clinical
(Conditional)
Low
Low
N/A
Low
Amphotericin B dosing based on

clinical indication. No dosage Case report supposes that liposomal amphotericin interferes w
adjustments recommended in setting
of ECMO (Conditional)
Low
Not graded (ex vivo

study)
Fluconazole dosing based on clinical
indication. Consider using loading
dose at therapy initiation. No dosage
adjustments recommended in setting
of ECMO (Conditional)
Low
Posaconazole dosing based on clinical
Low
Consider TDM for treatment dosing.
Low
Sulfamethoxazole-trimethoprim
dosing based on clinical indication. No
dosage adjustments recommended in
setting of ECMO. (Conditional)
Low
Azithromycin dosing based on clinical

Low
(Conditional)
Low
Linezolid dosing based on clinical
recommended in the setting of ECMO.
Patients on ECMO may fail to reach PK
targets with standard dosing of
linezolid, which could result in
treatment failure. (Conditional)
Low
Low
Low
Low
Low
Low
Refer to Intravenous Vancomycin Use

– Adult –
Inpatient/Ambulatory Clinical Practice
N/A Guideline for empiric dosing and
monitoring strategy. No empiric dose
adjustments recommended in the
setting of ECMO (Conditional)
Low
Low
Low
Low
Daptomycin dosing based on clinical

indication. No dosage adjustment
NA
(Conditional)
AUC0-24/MIC >/= 125 for gram

negative infections, >/=40 for gram
positive infections (Sinnah, et al)
N/A
Ciprofloxacin dosing based on clinical
(Conditional)
Low
Levofloxacin dosing based on clinical
(Conditional)
Moxifloxacin dosing based on clinical

(Conditional)
Gentamicin dosing based on clinical indication

and other patient-specific factors. Do dosage
adjustments recommended in setting of
ECMO. See Pharmacokinetic and
Pharmacodynamic Dose Optimization of
Antibiotics (β-lactams, aminoglycosides, and
Low ciprofloxacin) for the Treatment of Gram-
Negative Infections - Adult -
Inpatient/Emergency Department Clinical
Practice
Guideline for detailed dosage
recommendations. (Conditional)
Tobramycin dosing based on clinical indication

and other patient-specific factors. Do dosage
adjustments recommended in setting of
ECMO. See Pharmacokinetic and
Pharmacodynamic Dose Optimization of
Antibiotics (β-lactams, aminoglycosides, and
Low ciprofloxacin) for the Treatment of Gram-
Negative Infections - Adult -
Inpatient/Emergency Department Clinical
Practice
Guideline for detailed dosage
recommendations. (Conditional)
Moderate
** Want to discuss this one **
Leaning towards recommending 25

mg/kg as initial dosing because 2/4 of
these studies evaluated this dosing
regimen and still found considerable
proportion of patients who failed to
achieve target Cmax of 60-80 mg/L.
Could also look at our susceptibility

data to determine if failure to acheive
** Want to discuss this one **
Leaning towards recommending 25

mg/kg as initial dosing because 2/4 of
Moderate these studies evaluated this dosing
regimen and still found considerable
proportion of patients who failed to
achieve target Cmax of 60-80 mg/L.
Could also look at our susceptibility

data to determine if failure to acheive
this will result in high likelihood of
therapeutic failure. Might be ok to
use standard dosing if low MICs,
however if we are getting to amikacin
it likely means the patient has a
resistant organism we probably don't
Moderate want to mess around with
underdosing.
Low
Moderate
Oseltamivir dosing based on clinical

indication. No dosage adjusments
N/A
(Conditional)
indication. No dosage adjusments
(Conditional)
Low
PK efficacy target for ganciclovir

not well defined. Wiltshire et al
Ganciclovir dosing based on clinical recommend AUC-24 between 40-
indiction. No dosage adjustments 50 mg*r/L for CMV treatment
Low
(Conditional)
Notes / figures
Monte Carlo simulations
Per C Baus: target therapeutic trough range 1-2 for most
patients. May target >2 in some patient populations (CNS
infections, Heme/BMT). Toxicity most likely to occur with trough
levels >4. (review article states toxicity at trough concentration
>5-6). Ex vivo studies suggest extraction of voriconazole by the
oxygenator - may not be demonstrable by the PK profile, but
found 71% loss of voriconazole when comparing pre- and post-
oxygenator levels.
Per Andes (2018 J Antimicrob Chemother), no large scale trials to determine

efficacy/toxicity thresholds for isavuconzazole. Less inter-patient variability in PK
parameters when compared to other azole antifungals. TDM not routinely necessary.
Did not recommend TDM because of the above statements, even though they did this in
the case report. They did not provide justification for the goal trough they chose.
at liposomal amphotericin interferes with circuit flows and necessitated circuit exhange (Branick, et al)
Huddsini, et al (2011 Pharmacotherapy) state that PK alterations in posaconazole are less
frequent than with other antifungals such as voriconazole and are primarily related to
conditions causing decreased absorption. Do not recommend TDM for posaconazole due
to failure of current data to prove a correlation between serum posaconazole levels and
efficacy/toxicity.
IDSA recommends monitoring serum trough concentrations of posaconazole when the IR

suspension is used due to inconsistent bioavailability. Recommend target trough of >/=
0.7 for prophylaxis indications and >/= 1 for treatment indications with a note to increase
trough goal to 1.25 mg/L if response is poor. (Cite newer evidence than
pharmacotherapy review)
Sulfamethoxazole target peak range for PJP is 100-150 mcg/mL

(doi: 10.1016/j.curtheres.2014.08.003), although this is not well
defined and other studies have shown that there is no difference
in the rate of clinical failure between peak 100-150 and <100. It
has been proposed that toxicity is more likely >150/200 mcg/ml
but this has not been adequately proven (DOI:
10.1097/FTD.0000000000000282)
"One study conducted in seriously ill adult patients, higher

success rates were achieved when the cumulative percentage of
a 24-h period that the drug concentration exceeded the MIC
under steady-state pharmacokinetic conditions (%T>MIC)
exceeded 85% of the dosing interval and AUC/MIC ratios were
between 80 and 120" (Pea, et al)
Several of the included studies looked at PTA for different
vancomycin regimens. Since UW uses a individualized dosing
strategy based on TBW and CrCl, determined that these were
not relevant to this institution and were excluded from
discussion of the studies.

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ECMO Dosing Table

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LogP Protein Vd

Dhanani JA, Lipman J, Pincus J, et al.

Cheng V, Abdul-Aziz MH, Burrows F, et al.

Donadello K, Antonucci E, Cristallini S, et al. β-

Kühn D, Metz C, Seiler F, et al. Antibiotic

Fillâtre P, Lemaitre F, Nesseler N, et al. Impact of

Tazobactam: Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

Kühn D, Metz C, Seiler F, et al. Antibiotic

Seddon MM, Busey KV, Kutner SB, Mejia RE,

(-)0.86 to -3.8 20% 0.23-0.31

Chen W, Zhang D, Lian W, et al. Imipenem

Jaruratanasirikul S, Boonpeng A, Nawakitrangsan M,

(-)2.4 ~2% 15-20 L Donadello K, Antonucci E, Cristallini S, et al. β-

Hanberg P, Öbrink-Hansen K, Thorsted A, et al.

Kühn D, Metz C, Seiler F, et al. Antibiotic

Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

Voriconazole 58% 4.6 L/kg

Ruiz S, Papy E, Da Silva D, et al. Potential

Zhao Y, Seelhammer TG, Barreto EF, Wilson JW.

Honore PM, De Bels D, Gutierrez LB, et al.

Watt KM, Cohen-Wolkowiez M, Williams DC, et al.

Mourvillier B, Jullien V, Trouillet J, et al. Increase

Cabanilla MG, Villalobos N. A successful daptomycin

Foulquier JB, Berneau P, Frérou A, et al. Liposomal

Watt KM, Cohen-Wolkowiez M, Williams DC, et al.

Class: Other antibiotics

Turner RB, Rouse S, Elbarbry F, Wanek S, Grover V,

Nikolos P, Osorio J, Mohrien K, Rose C.

31% 0.65 L/kg

Cheng V, Abdul-Aziz MH, Burrows F, et al.

Jung Y, Lee DH, Kim HS. Prospective Cohort Study of

Donadello K, Roberts JA, Cristallini S, et al.

Moore JN, Healy JR, Thoma BN, et al. A Population

Park SJ, Yang JH, Park HJ, et al. Trough

Mahmoud AA, Avedissian SN, Al-Qamari A, Bohling

Wu CC, Shen LJ, Hsu LF, Ko WJ, Wu FL.

Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

Cabanilla MG, Villalobos N. A successful daptomycin

(-)1.1 20-40% 2.1-2.7 L/kg

~30-50% 1.7-2.7 L/kg

(-)4.1 <30% 0.2-0.3 L/kg

Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

(-)6.2 <30% 0.2-0.3 L/kg

Ruiz-Ramos J, Gimeno R, Pérez F, et al.

(-)7.9 0-11% 0.25 L/kg

(-)7.9 0-11% 0.25 L/kg

Bouglé A, Dujardin O, Lepère V, et al. PHARMECMO:

Dhanani JA, Lipman J, Pincus J, et al.

Protocol only, no results

Need to request from interlibrary loan

Ex vivo study (don't include)

Ex vivo study (don't include)

Found similar V0 and Cl compared to previously discussed population PK studies.

THIS STUDY IS NOT VERY GOOD FOR VANCO, considering excluding

evaluates a single patient on VV ECMO and CVVH, will not inlcude

Ceftriaxone dosing based on clinical

Cefepime dosing based on clinical

Cefazolin dosing based on clinical

CrCl > 20 ml/min: Piperacillin-

** Could consider continuous

Oxacillin dosing based on clinical

Imipenem-Cilastatin dosing based on

CrCl < 20 or iHD: meropenem dose

High vs Moderate ** recommendation based on

Want to discuss this one