Farinella Anita, Salvagno Michele, Minini Andrea, Attanasio Laila, Cunha Ana, Menozzi Marco, Saravia Andres, Amado Filipe, Gorham Julie, Hites Maya, Taccone Fabio Silvio, Gouvêa Bogossian Elisa
Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Route de Lennik, 808, 1070 Brussels, Belgium.
Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione-IRCCS ISMETT, 90127 Palermo, Italy.
Life (Basel). 2025 May 2;15(5):739. doi: 10.3390/life15050739.
Antimicrobial resistance (AMR) is a worldwide healthcare emergency. Whether insufficient beta-lactam antibiotic concentrations can be associated with AMR emergence remains controversial. This is a retrospective single-center cohort study including patients admitted to the intensive care unit of a tertiary university hospital from 2009 to 2014, who required a broad-spectrum beta-lactam antibiotic and had at least one therapeutic drug monitoring (TDM). Patients were categorized as having inadequate drug levels if the trough concentration (Cmin) fell below the clinical breakpoint for . AMR was defined according to breakpoints recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) using the disk diffusion method. A total of 444 patients (male sex, = 313, 71%; female sex, = 131, 29%; mean age 58 ± 15 years) were enrolled in the study. Patients received piperacillin/tazobactam ( = 168), ceftazidime/cefepime ( = 58) or meropenem ( = 218); among them, 65 (15%) had insufficient drug levels. Nine of these 65 (13.8%) patients with insufficient antibiotic levels acquired at least one pathogen with AMR within 15 days of TDM, when compared to 84/379 (22%) in the other group (OR 0.56 [95%CI 0.27-1.19]; = 0.13). In a multivariable competing-risk analysis including male gender, APACHE score on admission, previous colonization by other MDR bacteria, urinary catheter, central venous catheter, mechanical ventilation, previous hospitalization and previous surgery, insufficient antibiotic levels were not associated with AMR acquisition (sHR 0.84 [95% CI 0.42-1.68]). Similar results were found when a higher threshold was used to define insufficient drug levels (C < 4 times the clinical breakpoint). In conclusion, insufficient beta-lactam levels were not independently associated with AMR acquisition. Future prospective studies are needed to evaluate better the relationship between low drug levels and antibiotic resistance acquisition.
抗菌药物耐药性（AMR）是一个全球性的医疗紧急情况。β-内酰胺类抗生素浓度不足是否与AMR的出现有关仍存在争议。这是一项回顾性单中心队列研究，纳入了2009年至2014年在一所三级大学医院重症监护病房住院的患者，这些患者需要使用广谱β-内酰胺类抗生素且至少进行了一次治疗药物监测（TDM）。如果谷浓度（Cmin）低于临床断点，则将患者归类为药物水平不足。根据欧洲抗菌药物敏感性试验委员会（EUCAST）推荐的断点，采用纸片扩散法定义AMR。共有444例患者（男性313例，占71%；女性131例，占29%；平均年龄58±15岁）纳入研究。患者接受哌拉西林/他唑巴坦（168例）、头孢他啶/头孢吡肟（58例）或美罗培南（218例）治疗；其中65例（15%）药物水平不足。这65例抗生素水平不足的患者中有9例（13.8%）在TDM后15天内获得了至少一种具有AMR的病原体，而另一组为84/379例（22%）（比值比0.56 [95%可信区间0.27 - 1.19]；P = 0.13）。在一项多变量竞争风险分析中，包括男性、入院时的急性生理与慢性健康状况评分系统（APACHE）评分、先前是否被其他多重耐药菌定植、导尿管、中心静脉导管、机械通气、先前住院史和先前手术史，抗生素水平不足与AMR的获得无关（校正危险比0.84 [95%可信区间0.42 - 1.68]）。当使用更高的阈值来定义药物水平不足（C < 临床断点的4倍）时，也得到了类似的结果。总之，β-内酰胺类药物水平不足与AMR的获得没有独立关联。未来需要进行前瞻性研究，以更好地评估低药物水平与抗生素耐药性获得之间的关系。
