PMID- 35331299 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220401 IS - 1466-609X (Electronic) IS - 1364-8535 (Print) IS - 1364-8535 (Linking) VI - 26 IP - 1 DP - 2022 Mar 24 TI - The pathogens of secondary infection in septic patients share a similar genotype to those that predominate in the gut. PG - 68 LID - 10.1186/s13054-022-03943-z [doi] LID - 68 AB - BACKGROUND: Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. METHODS: In this prospective, observational case-control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. RESULTS: The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. CONCLUSION: Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment. CI - (c) 2022. The Author(s). FAU - Mu, Sucheng AU - Mu S AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Xiang, Hao AU - Xiang H AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Wang, Yuezhu AU - Wang Y AD - NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, 2140 Xietu Road, Shanghai, China. AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai and Shanghai Institute for Biomedical and Pharmaceutical Technologies, 250 Bibo Road, Shanghai, China. FAU - Wei, Wei AU - Wei W AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Long, Xiangyu AU - Long X AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Han, Yi AU - Han Y AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Kuang, Zhongshu AU - Kuang Z AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Yang, Yilin AU - Yang Y AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Xu, Feixiang AU - Xu F AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Xue, Mingming AU - Xue M AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Dong, Zhimin AU - Dong Z AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. FAU - Tong, Chaoyang AU - Tong C AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. tong.chaoyang@zs-hospital.sh.cn. FAU - Zheng, Huajun AU - Zheng H AD - NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, 2140 Xietu Road, Shanghai, China. zhenghj@chgc.sh.cn. FAU - Song, Zhenju AU - Song Z AUID- ORCID: 0000-0002-3068-4795 AD - Department of Emergency Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. song.zhenju@zs-hospital.sh.cn. AD - Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, China. song.zhenju@zs-hospital.sh.cn. AD - Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, China. song.zhenju@zs-hospital.sh.cn. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20220324 PL - England TA - Crit Care JT - Critical care (London, England) JID - 9801902 RN - 0 (RNA, Ribosomal, 16S) SB - IM MH - Animals MH - Case-Control Studies MH - *Coinfection MH - Genotype MH - Humans MH - Mice MH - Prospective Studies MH - RNA, Ribosomal, 16S/genetics MH - *Sepsis/drug therapy PMC - PMC8944137 OTO - NOTNLM OT - Bacterial translocation OT - Gut microbiota OT - Secondary nosocomial infection OT - Sepsis COIS- The authors declare no conflicts of interest. EDAT- 2022/03/26 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/03/24 CRDT- 2022/03/25 05:31 PHST- 2021/11/24 00:00 [received] PHST- 2022/03/07 00:00 [accepted] PHST- 2022/03/25 05:31 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2022/03/24 00:00 [pmc-release] AID - 10.1186/s13054-022-03943-z [pii] AID - 3943 [pii] AID - 10.1186/s13054-022-03943-z [doi] PST - epublish SO - Crit Care. 2022 Mar 24;26(1):68. doi: 10.1186/s13054-022-03943-z.