Roux Damien, Benichou Nicolas, Hajage David, Martin-Lefèvre Laurent, de Prost Nicolas, Lerolle Nicolas, Titeca-Beauport Dimitri, Boulet Eric, Mayaux Julien, Mégarbane Bruno, Mahjoub Khaoula, Carpentier Dorothée, Nseir Saad, Tubach Florence, Ricard Jean-Damien, Dreyfuss Didier, Gaudry Stéphane
DMU ESPRIT, Service de Médecine Intensive Réanimation, AP-HP, Université Paris Cité, Hôpital Louis Mourier, 92700, Colombes, France.
Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, 75015, Paris, France.
Ann Intensive Care. 2023 Feb 25;13(1):11. doi: 10.1186/s13613-023-01105-0.
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.
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.
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.
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.
The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.
脓毒症的预后与早期抗生素使用的充分性相关。这种充分性取决于抗菌谱、细菌耐药情况和抗生素剂量。β-内酰胺类药物的最佳疗效要求全天尽可能长时间维持高于目标细菌最低抑菌浓度（MIC）的血药浓度。脓毒症相关性急性肾损伤（AKI）是重症监护病房（ICU）中最常见的AKI综合征，常需启动肾脏替代治疗（RRT）。严重AKI和RRT均可能增加抗生素血药浓度超出目标范围，最终改变患者预后。
这是一项对随机对照试验的二次分析，该试验比较了620例患有严重AKI（根据KDIGO标准3级定义）的危重症患者早期与延迟启动RRT的策略。我们比较了两种RRT启动策略之间β-内酰胺类药物的谷浓度。主要结局是β-内酰胺类药物谷血浆浓度足够（定义为谷浓度高于MIC的4倍）的患者比例。我们假设与分配至延迟策略组的患者相比，早期启动RRT可能与抗生素血浆谷浓度不足相关。
纳入112例患者：早期组53例，延迟组59例。纳入时83例患者（74%）患有脓毒症休克。总体人群中80.4%（n = 90）的患者β-内酰胺类药物谷血浆浓度高于MIC断点的4倍，早期组与延迟组之间无差异（分别为79.2%和81.4%，p = 0.78）。多因素分析显示，脓毒症休克的存在和较高的平均动脉压与抗生素谷浓度足够的可能性显著相关[比值比（OR）分别为3.95（1.14；13.64），p = 0.029和OR 1.05（1.01；1.10），p = 0.013]。无论β-内酰胺类药物谷浓度是否高于MIC的4倍，降钙素原水平变化、无儿茶酚胺天数以及死亡率均无差异。
在这项对随机对照试验的二次分析中，肾脏替代治疗启动策略对患有严重AKI的ICU患者β-内酰胺类药物的血浆谷浓度无显著影响。纳入时存在脓毒症休克是与β-内酰胺类药物浓度足够相关的主要变量。
AKIKI试验在纳入首例患者之前已在ClinicalTrials.gov注册（标识符：NCT01932190）。
