We agree with the recent commentary of Gonçalves-Pereira and Oliveira refuting a ‘one
size fits all’ paradigm of antibiotic dosing in patients subjected to extracorporeal
circulation 1] but want to focus somewhat further on meropenem pharmacokinetics (PK).
Meropenem has optimal bactericidal activity if plasma levels remain above the minimum
inhibitory concentration of the pathogen for at least 40Â % of the dosing interval.
Still, many patients with severe sepsis do not attain this PK target, have unpredictable
PK changes or show large individual and inter-patient variability in distribution
volume and clearance when treated with recommended meropenem doses 2], 3].
Meropenem is degraded and significantly sequestered in the extracorporeal membrane
oxygenation (ECMO) circuit after 4 to 6Â h of treatment. ECMO also induces a systemic
inflammatory response which, independently of underlying sepsis, impairs normal meropenem
PK 4]. Thus, optimization of meropenem treatment during ECMO requires either more frequent
dosing, a dose increase, or prolonged infusion. Ideally, meropenem should be infused
continuously over 24Â h but, due to its relative instability at room temperature, only
a 3-hour infusion is safely feasible. We suggest to administer a 3-hour infusion of
2Â g meropenem every 6Â h 4]. Future adaptations must be anticipated. We refer to the recently proposed concept
of ‘dose modulation’, which concentrates the largest weight of antibiotics front-end
when the microbial load is highest and gradually reduces antibiotic dose as sepsis
improves 5]. This would imply increasing the loading dose of meropenem (4Â g?) and ensuring an
adequate maintenance dose guided by PK parameters.