Centro Superior de Investigación en Salud Pública-FISABIO, Valencia, Spain.
Hospital Universitari i Politècnic La Fe, Valencia, Spain.
Antimicrob Agents Chemother. 2020 Jan 27;64(2). doi: 10.1128/AAC.01415-19.
Multidrug-resistant (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here, we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as species that acquired nonsusceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e., meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam ( < 0.001) but not with nonsusceptible strains. We report previously unobserved inter- and intraindividual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut-colonizing pathogens for future clinical studies and in clinical decision-making.
多药耐药菌（MRE）无症状定植于肠道，然后从肠道侵入血液，导致危及生命的感染，尤其是在严重定植的患者中。尽管 MRE 定植水平具有临床相关性，但我们对住院患者中 MRE 定植水平的变化以及决定这些水平的临床因素知之甚少。在这里，我们通过对 133 例急性白血病患者进行纵向跟踪，对 MRE 粪便水平进行了迄今为止最大规模的研究之一，并通过广泛培养来监测他们的 MRE 水平随时间的变化。MRE 被定义为在≥3 种抗菌药物类别中对≥1 种药物获得非敏感性的物种。此外，由于使用了选择性培养基，MRE 必须对第三代头孢菌素具有耐药性。在 60%的患者中检测到了 MRE，但它们的粪便水平在患者之间和同一患者内差异很大（分别为>6 和 4 个数量级）。对临床元数据的多变量分析显示，静脉内使用β-内酰胺类药物（即美罗培南和哌拉西林他唑巴坦）对 MRE 粪便水平有显著影响，显著降低了住院患者的粪便 MRE 水平。与β-内酰胺类药物的直接作用一致，我们仅在患者定植的菌株对所使用的β-内酰胺类药物敏感时（<0.001）发现了这种影响，而不是对不敏感的菌株。我们报告了以前未观察到的 MRE 粪便水平的个体间和个体内异质性，表明定量监测比定性监测住院患者更具信息性。此外，我们的研究强调了在未来的临床研究和临床决策中纳入定植于肠道的病原体的抗生素治疗和敏感性数据的相关性。
