Clinical Microbiology and Parasitology Department, Hospital Universitario La Pazgrid.81821.32, IdiPAZ, Madrid, Spain.
Pediatric Hepatology Department, Hospital Universitario La Pazgrid.81821.32, IdiPAZ, Madrid, Spain.
Microbiol Spectr. 2022 Dec 21;10(6):e0284222. doi: 10.1128/spectrum.02842-22. Epub 2022 Nov 8.
Pediatric liver transplantation (PLTx) is commonly associated with extensive antibiotic treatments that can produce gut microbiome alterations and open the way to dominance by multidrug-resistant organisms (MDROs). In this study, the relationship between intestinal Relative Loads (RLs) of β-lactamase genes, antibiotic consumption, microbiome disruption, and the extraintestinal dissemination of MDROs among PLTx patients is investigated. 28 PLTx patients were included, from whom 169 rectal swabs were collected. Total DNA was extracted and , , , and were quantified via quantitative polymerase chain reaction (qPCR) and normalized to the total bacterial load () through LogΔΔCt to determine the RLs. sequencing was performed for 18 samples, and metagenomic sequencing was performed for 2. Patients' clinical data were retrieved from the hospital's database. At least one of the genes tested were detected in all of the patients. The RLs for , , , and were higher than 1% of the total bacterial population in 67 (80.73%), 56 (78.87%), 57 (77.03%) and 39 (61.9%) samples, respectively. High RLs for , , and/or , were positively associated with the consumption of carbapenems with trimethoprim-sulfamethoxazole and coincided with low diversity in the gut microbiome. Low RLs were associated with the consumption of noncarbapenem β-lactams with aminoglycosides ( < 0.05). Extraintestinal isolates harboring the same gene(s) as those detected intraintestinally were found in 18 samples, and the RLs of the respective swabs were high. We demonstrated a relationship between the consumption of carbapenems with trimethoprim-sulfamethoxazole, intestinal dominance by MDROs and extraintestinal spread of these organisms among PLTx patients. In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients. Moreover, the high loads of resistance genes were related to the extraintestinal spread of multidrug-resistant organisms. Together, our data show that the tracking of the relative intestinal loads of antibiotic resistance genes can be used as a biomarker that has the potential to stop the extraintestinal spread of antibiotic-resistant bacteria via the measurement of the intestinal dominance of these organisms, thereby allowing for the application of preventive measures.
儿科肝移植（PLTx）通常需要广泛使用抗生素治疗，这可能导致肠道微生物组发生改变，并为多药耐药菌（MDRO）的优势生长开辟道路。在这项研究中，我们研究了 PLTx 患者肠道β-内酰胺酶基因相对负荷（RL）、抗生素消耗、微生物组破坏以及 MDRO 向肠道外传播之间的关系。共纳入 28 例 PLTx 患者，采集 169 份直肠拭子。提取总 DNA，通过定量聚合酶链反应（qPCR）定量 、 、 、 ，并通过 LogΔΔCt 标准化到总细菌负荷（），以确定 RL。对 18 个样本进行 16S 测序，对 2 个样本进行宏基因组测序。从医院数据库中检索患者的临床数据。所有患者均检测到至少一种基因。在 67 例（80.73%）、56 例（78.87%）、57 例（77.03%）和 39 例（61.9%）样本中， 、 、 、 和 的 RL 高于总细菌群的 1%。 、 、 和/或 的高 RL 与碳青霉烯类药物与甲氧苄啶-磺胺甲恶唑的消耗呈正相关，并且与肠道微生物组的低多样性相吻合。低 RL 与非碳青霉烯类 β-内酰胺类药物与氨基糖苷类药物的消耗有关（<0.05）。在 18 个样本中发现了与肠道内相同基因（s）一致的肠道外分离株，相应拭子的 RL 较高。我们证明了碳青霉烯类药物与甲氧苄啶-磺胺甲恶唑的消耗、MDRO 对肠道的优势生长以及这些生物体在 PLTx 患者中的肠道外传播之间存在关联。在这项研究中，我们跟踪了儿科肝移植患者肠道中抗生素耐药基因的相对负荷，并确定了这种负荷、抗生素消耗和抗生素耐药生物体引起的感染之间的关系。我们证明，广谱抗生素的消耗增加了这种负荷，并降低了这些患者肠道微生物组的多样性。此外，高耐药基因负荷与多药耐药菌的肠道外传播有关。综上所述，我们的数据表明，抗生素耐药基因相对肠道负荷的跟踪可以作为一种生物标志物，通过测量这些生物体对肠道的优势生长，有可能阻止抗生素耐药细菌的肠道外传播，从而可以采取预防措施。
