Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Université Limoges, INSERM, CHU Limoges, UMR 1092, Limoges, France.
Microbiome. 2017 Aug 14;5(1):88. doi: 10.1186/s40168-017-0309-z.
The gut microbiota is a reservoir of opportunistic pathogens that can cause life-threatening infections in critically ill patients during their stay in an intensive care unit (ICU). To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed "selective decontamination of the digestive tract" (SDD), is used in some countries where it improves clinical outcome in ICU patients. Yet, the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown. Here, we characterize the composition of the gut microbiota and its antimicrobial resistance genes ("the resistome") of ICU patients during SDD and of healthy subjects.
From ten patients that were acutely admitted to the ICU, 30 fecal samples were collected during ICU stay. Additionally, feces were collected from five of these patients after transfer to a medium-care ward and cessation of SDD. Feces from ten healthy subjects were collected twice, with a 1-year interval. Gut microbiota and resistome composition were determined using 16S rRNA gene phylogenetic profiling and nanolitre-scale quantitative PCRs. The microbiota of the ICU patients differed from the microbiota of healthy subjects and was characterized by lower microbial diversity, decreased levels of Escherichia coli and of anaerobic Gram-positive, butyrate-producing bacteria of the Clostridium clusters IV and XIVa, and an increased abundance of Bacteroidetes and enterococci. Four resistance genes (aac(6')-Ii, ermC, qacA, tetQ), providing resistance to aminoglycosides, macrolides, disinfectants, and tetracyclines, respectively, were significantly more abundant among ICU patients than in healthy subjects, while a chloramphenicol resistance gene (catA) and a tetracycline resistance gene (tetW) were more abundant in healthy subjects.
The gut microbiota of SDD-treated ICU patients deviated strongly from the gut microbiota of healthy subjects. The negative effects on the resistome were limited to selection for four resistance genes. While it was not possible to disentangle the effects of SDD from confounding variables in the patient cohort, our data suggest that the risks associated with ICU hospitalization and SDD on selection for antibiotic resistance are limited. However, we found evidence indicating that recolonization of the gut by antibiotic-resistant bacteria may occur upon ICU discharge and cessation of SDD.
肠道微生物群是机会性病原体的储库，这些病原体在重症监护病房（ICU）住院的危重患者中可能导致危及生命的感染。为了抑制肠道机会性病原体的定植，在一些国家使用了一种预防性抗生素方案，称为“选择性消化道去污染”（SDD），该方案可改善 ICU 患者的临床预后。然而，ICU 住院和 SDD 对肠道微生物群的影响在很大程度上仍不清楚。在这里，我们描述了 SDD 期间 ICU 患者和健康受试者的肠道微生物群组成及其抗菌药物耐药基因（“耐药组”）。
从 10 名急性入住 ICU 的患者中，在 ICU 住院期间采集了 30 份粪便样本。此外，在将其中 5 名患者转至中等护理病房并停止 SDD 后，从这些患者中采集了粪便样本。从 10 名健康受试者中采集了粪便样本两次，间隔 1 年。使用 16S rRNA 基因系统发育分析和纳升级定量 PCR 来确定肠道微生物群和耐药组的组成。与健康受试者相比，ICU 患者的微生物群不同，其特征为微生物多样性降低、大肠杆菌水平降低以及厌氧革兰氏阳性但丁酸产生菌的梭菌属 IV 和 XIVa 减少，而拟杆菌门和肠球菌增加。与健康受试者相比，4 种耐药基因（分别提供对氨基糖苷类、大环内酯类、消毒剂和四环素的耐药性）在 ICU 患者中明显更丰富，而氯霉素耐药基因（catA）和四环素耐药基因（tetW）在健康受试者中更丰富。
SDD 治疗的 ICU 患者的肠道微生物群与健康受试者的肠道微生物群有很大的不同。对耐药组的负面影响仅限于对 4 种耐药基因的选择。尽管在患者队列中无法将 SDD 的影响与混杂变量分开，但我们的数据表明，与 ICU 住院和 SDD 相关的抗生素耐药选择风险是有限的。然而，我们发现的证据表明，在 ICU 出院和停止 SDD 后，肠道可能会被抗生素耐药细菌重新定植。
