Characteristics and Epidemiology of Extended-Spectrum beta-Lactamase-Producing Multidrug-Resistant Klebsiella pneumoniae From Red Kangaroo, China
FRONTIERS IN MICROBIOLOGY
Authors: Wang, Xue; Kang, Qian; Zhao, Jianan; Liu, Zhihui; Ji, Fang; Li, Junbao; Yang, Jianchun; Zhang, Chenglin; Jia, Ting; Dong, Guoying; Liu, Shelan; Hu, Guocheng; Qin, Jianhua; Wang, Chengmin
Abstract
Due to its drug resistant nature, beta-lactamase represents a serious challenge for public health. Extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae clones are increasingly reported worldwide. Little is known about the prevalence and biological characteristics of drug-resistant strains in zoos. During routine surveillance at the Zhengzhou Zoo of China, we found Klebsiella pneumoniae isolate in healthy Red Kangaroos (Macropus Rufus) with severe MDR. The Klebsiella pneumoniae were especially resistant to Cefuroxime Sodium (MIC, > 64 mu g/mL), Ceftriaxone (MIC, >8 mu g/mL) and Cefepime (MIC, >64 mu g/mL), and belonged to ST290. Subsequently, whole genome sequencing (WGS) showed that the Chrome Chr-M297-1 harbored bla(DHA-3), bla(SHV-1), bla(CTX-M-14), fosA5, dfrA3, sul3, etc., and pM297-1.1 [222,864 bp, IncFIB(K)], which carried nine antimicrobial genes including bla(CTX-M-14), bla(TEM-191), aph(3 '')-Ib, aph(6)-Id and qnrS1, etc., and pM297-1.2 [225,763 bp, IncFII(K)] carried 22 antimicrobial genes including bla(TEM-1), bla(CTX-M-3), aph(3 ')-Ia, aac(3)-IIa, aac(6 ')-Ib-cr, aadA16, qnrB2, qnrS1, qacE Delta 1, mphA, sul1, and dfrA27, etc. A traceability analysis then revealed that these two plasmids were highly similar to those recovered from human clinical samples in some southern cities in Sichuan Province, China (>99%), suggesting that these plasmids are spreading in China. Furthermore, two plasmids harboring conjugal transfer genes facilitated the transmission of antimicrobial genes by conjugation with E. coli J53. Our research shows that the transmission and adaptation of Klebsiella pneumoniae producing ESBLs is occurring in zoo environments, suggesting that zoos may be becoming important potential reservoirs for clinically important drug-resistant genes. It is therefore necessary to monitor the emergence and spread of drug-resistant gene strains in captive wild animals held in zoo environments.
Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn's Disease
INFLAMMATORY BOWEL DISEASES
Authors: Osterman, Mark T.; Gordon, Ilyssa O.; Davis, Elisabeth M.; Ciorba, Matthew; Glover, Sarah C.; Abraham, Bincy; Khan, Freeha; Guo, Xueyan; Yee, Eric U.; Allard, Felicia D.; Claggett, Brian; Shen, Bo; Liu, Julia J.
Abstract
Objective: Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn's disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. Design: Crohn's disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of >= 5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Results: One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3-48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03-7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change. Conclusions: Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.