Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study—an ancillary study of a randomized controlled trial

Damien Roux (1, 2) , Nicolas Benichou (3, 1) , David Hajage (4, 5, 6) , Laurent Martin-Lefèvre (7, 8) , Nicolas de Prost (9, 10) , Nicolas Lerolle (11) , Dimitri Titeca-Beauport (12, 13) , Eric Boulet (14) , Julien Mayaux (6) , Bruno Mégarbane (15, 16) , Khaoula Mahjoub (17) , Dorothée Carpentier (18) , Saad Nseir (19, 20) , Florence Tubach (21, 22, 6) , Jean-Damien Ricard (1, 23) , Didier Dreyfuss (1, 3) , Stéphane Gaudry (24, 3)

1 Hôpital Louis Mourier - AP-HP [Colombes]
2 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
3 CoRaKID - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée
4 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
5 PEPITES - Pharmacoépidémiologie et évaluation des soins [iPLesp]
6 CHU Pitié-Salpêtrière [AP-HP]
7 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
8 CHU Nantes - Centre Hospitalier Universitaire de Nantes
9 CHU Henri Mondor [Créteil]
10 CARMAS - Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis)
11 CHU Angers - Centre Hospitalier Universitaire d'Angers
12 CHU Amiens-Picardie
13 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
14 Hopital Réné Dubos
15 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
16 Hôpital Lariboisière-Fernand-Widal [APHP]
17 Hôpital Delafontaine
18 CHU Rouen
19 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
20 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
21 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
22 ECEVE (U1123 / UMR_S_1123) - Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables
23 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
24 Hôpital Avicenne [AP-HP]

Background Sepsis prognosis correlates with antibiotic adequacy at the early phase. This adequacy is dependent on antibacterial spectrum, bacterial resistance profile and antibiotic dosage. Optimal efficacy of beta-lactams mandates concentrations above the minimal inhibitory concentration (MIC) of the targeted bacteria for the longest time possible over the day. Septic acute kidney injury (AKI) is the most common AKI syndrome in ICU and often mandates renal replacement therapy (RRT) initiation. Both severe AKI and RRT may increase outside target antibiotic concentrations and ultimately alter patient’s prognosis. Patients and methods This is a secondary analysis of a randomized controlled trial that compared an early RRT initiation strategy with a delayed one in 620 critically ill patients undergoing severe AKI (defined by KDIGO 3). We compared beta-lactam trough concentrations between the two RRT initiation strategies. The primary outcome was the proportion of patients with sufficient trough plasma concentration of beta-lactams defined by trough concentration above 4 times the MIC. We hypothesized that early initiation of RRT could be associated with an insufficient antibiotic plasma trough concentration compared to patients allocated to the delayed strategy. Results One hundred and twelve patients were included: 53 in the early group and 59 in the delayed group. Eighty-three patients (74%) had septic shock on inclusion. Trough beta-lactam plasma concentration was above 4 times the MIC breakpoint in 80.4% ( n = 90) of patients of the whole population, without differences between the early and the delayed groups (79.2% vs. 81.4%, respectively, p = 0.78). On multivariate analysis, the presence of septic shock and a higher mean arterial pressure were significantly associated with a greater probability of adequate antibiotic trough concentration [OR 3.95 (1.14;13.64), p = 0.029 and OR 1.05 (1.01;1.10), p = 0.013, respectively). Evolution of procalcitonin level and catecholamine-free days as well as mortality did not differ whether beta-lactam trough concentration was above 4 times the MIC or not. Conclusions In this secondary analysis of a randomized controlled trial, renal replacement therapy initiation strategy did not significantly influence plasma trough concentrations of beta-lactams in ICU patients with severe AKI. Presence of septic shock on inclusion was the main variable associated with a sufficient beta-lactam concentration. Trial registration : The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.

Domaines: Médecine humaine et pathologie

Damien Roux, Nicolas Benichou, David Hajage, Laurent Martin-Lefèvre, Nicolas de Prost, et al.. Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study—an ancillary study of a randomized controlled trial. Annals of Intensive Care, 2023, 13 (1), pp.11. ⟨10.1186/s13613-023-01105-0⟩. ⟨hal-04031648⟩