Therapeutic drug monitoring of meropenem and piperacilin administered in continuous infusion. preliminary data

Torner, Mar Miralbés; Díaz, Fabián; Brügger, Sarah; Marrón, SM Cano; Schoenenberger, JA; Eroles, A Aragones; Casals, X. Nuvials; Vidal, Montserrat Vallverdú; Garrido, Belén; Martínez, Mercedes Palomar

doi:10.1186/2197-425x-3-s1-a394

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“…Maximum doses of 6000 mg/day, e.g., three times 2000 mg over 0.5 h or 3 h for meningitis, have previously been recommended [ 11 ]. Apart from that, off-label continuous regimens with 6000 mg daily preceded by loading doses of 2000 mg, or even 3500 mg every 6 h, have been reported [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Model-Informed Translation of In Vitro Effects of Short-, Prolonged- and Continuous-Infusion Meropenem against Pseudomonas aeruginosa to Clinical Settings

et al. 2022

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Pharmacokinetic-pharmacodynamic (PKPD) models have met increasing interest as tools to identify potential efficacious antibiotic dosing regimens in vitro and in vivo. We sought to investigate the impact of diversely shaped clinical pharmacokinetic profiles of meropenem on the growth/killing patterns of Pseudomonas aeruginosa (ARU552, MIC = 16 mg/L) over time using a semi-mechanistic PKPD model and a PK/PD index-based approach. Bacterial growth/killing were driven by the PK profiles of six patient populations (infected adults, burns, critically ill, neurosurgery, obese patients) given varied pathogen features (e.g. EC50, growth rate, inoculum), patient characteristics (e.g. creatinine clearance), and ten dosing regimens (including two dose levels and 0.5-h, 3-h and continuous-infusion regimens). Conclusions regarding the most favourable dosing regimen depended on the assessment of (i) the total bacterial load or fT>MIC (time that unbound concentrations exceed the minimum inhibitory concentration); (ii) the median or P0.95 profile of the population; and (iii) 8 h or 24 h time points. Continuous infusion plus loading dose as well as 3-h infusions (3-h infusions: e.g. for scenarios associated with low meropenem concentrations, P0.95 profiles, and MIC ≥ 16 mg/L) appeared superior to standard 0.5-h infusions at 24 h. The developed platform can serve to identify promising strategies of efficacious dosing for clinical trials.

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Section: Discussionmentioning

confidence: 99%