BackgroundChina has established an extensive multidisciplinary surveillance network encompassing antimicrobial utilisation, antimicrobial resistance, and nosocomial infections. We aimed to identify challenges and barriers in antimicrobial stewardship (AMS) development based on this national multidisciplinary surveillance network.MethodsThis cross-sectional study was conducted in 15 hospitals across China from July 2021 to April 2023. Purposeful sampling was employed to select the hospitals based on the rising prevalence of carbapenem-resistant Klebsiella pneumoniae. The survey consisted of three parts: a testing questionnaire was used to assess the awareness of clinical physicians regarding AMS; a scoring table was developed through the Delphi method to assess the hospitals' multidisciplinary management covering antibacterial usage surveillance, resistance surveillance, fungal surveillance, infectious disease management, and infection prevention and control; an on-site investigation based on case review and field inspection. Pearson correlation tests were used to examine the relationship between resistance levels and scores for various items. Theme analysis was applied to highlight key areas of focus in hospital multidisciplinary AMS from the on-site investigation.ResultsFindings revealed that physicians of respiratory, infectious disease, and critical care were the top 3 specialists in AMS awareness scores, with an average of 70 points, 65 points and 62.5 points, respectively (a full mark of 100 points). Performance in infectious disease management, antibacterial surveillance, and infection prevention and control showed a scoring rate over 70%, with relatively low scores in resistance surveillance (49.1%) and fungal surveillance (36.0%). No significant correlation was found between any single scoring item and the resistance levels of focused drug-resistance pathogens. Five key areas were identified for improving multidisciplinary AMS: organizational structure, staffing and training, drug formulary and prescription management, laboratory testing and quality control, and clinical sampling and data reporting.ConclusionsThe prevalence of focused drug-resistance pathogens could not attribute to any single factor. The following AMS activities should emphasise the establishment of sophisticated communication and collaboration mechanisms within multidisciplinary teams.Trial registrationApproval for this study was granted by the Ethics Committee of Peking University (reference number IRB00001052-22100).

As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro. Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud’s agar plates at 35 ℃. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB. Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays. MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.

To date, the genomic characterization of foodborne bacteria carrying the mobile colistin resistance gene mcr-1 and transferability of mcr-1-carrying plasmids between wild-type bacteria have not been studied in detail. We retrospectively investigated the prevalence of mcr-1-positive Salmonella and Escherichia coli isolated from retail food products, food supply chain, and clinical samples across China in the last decade (2006?2017). The horizontal transfer of mcr-1-bearing plasmids and their complete nucleotide sequence were characterized using conjugation, S1-nuclease pulsed-field gel electrophoresis, and Southern hybridization, coupled with Illumina and Nanopore sequencing. Twelve (0.67%) mcr-1-positive strains were identified from 1789 non-duplicated isolates, including 1283 Salmonella and 506 E. coli. Eleven (21.7%0) mcr-1-positive E. coli strains were identified from the isolates collected during 2006?2017, which was significantly more prevalent than mcr-1-positive Salmonella in this period (0.78%0, 1/1283; P < 0.05). All donors (nine mcr-1-positive isolates, designated as D1?9) were multidrug resistant with diverse antimicrobial susceptibility profiles and were resistant to polymyxin B. mcr-1carrying plasmids in donors were successfully transferred to recipients at frequencies of 4.6 ? 10-2 to 6.25 ? 10-4 per recipient cell. A -33 kb IncX4-type plasmid in D1, which carried mcr-1 with the insertion sequence IS26 upstream, was effectively transferred to recipient R1. D2, D4, and their corresponding transconjugants harbored a -60 kb IncI2-type plasmid with the insertion sequence ISApl1 upstream of mcr-1. A -60 kb conjugative mcr-1bearing plasmid derived from D5 also belonged to type IncI2 and contained the mcr-1 gene cassette ISEcp1-blaCTXM-55-mcr-1-PAP2. In conclusion, mcr-1 was commonly detected in type IncI2, IncX4, and IncHI2 plasmids and mcr-1 encoding colistin resistance was successfully transferred between foodborne and clinical strains of E. coli and Salmonella isolated in China. mcr-1 gene cassettes including IS26-mcr-1-PAP2, ISAPl1-mcr-1-PAP2, and ISEcp1-blaCTX-M-55-mcr-1-PAP2 can be transferred horizontally between wild-type bacteria via conjugation. The new mcr-1 gene cassette discovered in this study provided evidence for co-transfer of mcr-1 and other antibiotic resistance genes. This finding suggests that antibiotics, other than colistin, should be used in combination for the treatment and prevention of diseases caused by foodborne pathogens. The co-transfer of mcr-1 and other antibiotic resistance genes will also enhance antibiotic resistance in foodborne pathogens.

背景 住院病人血流感染的发病率逐年升高,引起了广大临床工作者的高度重视.目的 探讨我中心2018-2020年血培养病原菌的分布及耐药性变迁,为临床血流感染的诊治提供依据.方法 使用VITEK MS质谱仪进行细菌鉴定,VITEK 2 Compact细菌鉴定药敏仪进行抗菌药物敏感性试验,数据采用WHONET 5.6软件进行统计分析.结果 我中心2018-2020年3574例患者血培养阳性,其中男性多于女性,平均年龄58.26岁,60岁以上患者占53.05％(1896/3574).血培养阳性率排名前3位的科室分别为急诊科、重症监护室及肿瘤科.急诊血培养阳性患者多存在发热或腹痛等急性症状,且伴有不同组织脏器病变,以肺部感染最为常见.共检出非重复病原菌4426株,其中革兰阳性菌占57.82％,革兰阴性菌占38.12％,真菌占4.07％.前5位分离菌依次为凝固酶阴性葡萄球菌(1505株,34.00％)、大肠埃希菌(659株,14.89％)、肺炎克雷伯菌(469株,10.60％)、屎肠球菌(235株,5.31％)和金黄色葡萄球菌(135株,3.05％).2018-2020年大肠埃希菌对亚胺培南耐药率分别为3.04％、2.54％、2.52％,总体耐药率为2.58％;肺炎克雷伯菌对亚胺培南的耐药率分别为40.24％、33.33％、57.05％,总体耐药率为43.71％;鲍曼不动杆菌对亚胺培南的耐药率分别为73.68％、80.36％、75.00％,总体耐药率为76.40％;铜绿假单胞菌对亚胺培南的耐药率分别为18.52％、28.00％、39.29％,总体耐药率为26.17％.2018-2020年耐甲氧西林金黄色葡萄球菌的检出率分别为29.63％、17.39％、26.47％,总体检出率为26.61％.结论 解放军总医院第一医学中心血培养病原菌以凝固酶阴性葡萄球菌、大肠埃希菌和肺炎克雷伯菌为主,碳青霉烯耐药肺炎克雷伯菌和鲍曼不动杆菌的检出率较高,临床应高度重视.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

Faecal E. coli can act as reservoirs for resistance genes. Here, we analyzed prevalence of drug resistance in faecal E. coli isolated from healthy children at a single kindergarten in Beijing, China, then used whole genome sequencing to characterize fluoroquinolone-non-susceptible strains. Our results revealed high resistance to ampicillin (54.0%), trimethoprim/sulphurmethoxazole (47.5%) and tetracycline (58.9%) among 576 faecal E. coli isolates, 49.2% of which exhibited multidrug resistance. A total of 113 E. coli isolates were not susceptible to ciprofloxacin, with four sequence types, namely ST1193 (25.7%), ST773 (13.3%), ST648 (8.8%) and ST131 (7.1%) found to be the most prevalent (54.9%). With regards to resistance to quinolones, we detected chromosomal mutations in gyrA, parC, and parE in 111 (98.2%), 105 (92.9%), and 67 (61.1%) isolates, respectively. blaCTX-M (37.2%) was the major ESBL gene, whereas blaCTX-M-14 (12.4%) and blaCTX-M-27 (11.5%) were the most frequent subtypes. A total of 90 (79.6%) ExPEC and 65 (57.5%) UPEC isolates were classified. Overall, these findings revealed clonal spread of certain prevalent STs, namely ST1193, ST773, ST648 and ST131 E. coli isolates in healthy children within a single kindergarten in Beijing, China, affirming the seriousness of the multidrug resistance problem and potential pathogenicity of E. coli isolates in healthy children. Therefore, there is an urgent need for increased surveillance to enhance control of this problem.

目的 了解解放军总医院耳鼻喉外科耳道感染患者标本中分离的铜绿假单胞菌的人群分布、生物膜产生情况及耐药情况等流行病学特征,为临床提供重要依据.方法 采用Vitek MS质谱仪进行细菌鉴定,药敏试验采用纸片扩散法(K-B法)或Vitek 2 Compact全自动细菌鉴定药敏仪,按美国临床实验室标准化协会2016-M100的标准进行药敏结果分析,用结晶紫染色法检测铜绿假单胞菌生物膜并对生物膜形成能力进行判定.结果 2013-2017年解放军总医院共收集到与耳道感染相关的铜绿假单胞菌106株,各年龄段均有检出;形成生物膜的菌株占80.20％,复发病例分离的菌株中可形成生物膜的菌株比例(81.25％)高于未复发病例分离的菌株(78.57％);不同生物膜形成能力的菌株抗菌药物敏感率差异无统计学意义(P>0.05),产膜菌株对亚胺培南、头孢他啶和左氧氟沙星比未产膜菌株的敏感性略高;复发组与未复发组菌株的抗菌药物敏感性差异均无统计学意义(P>0.05),复发组的头孢他啶、亚胺培南、美罗培南、左氧氟沙星、哌拉西林、氨曲南和头孢哌酮/舒巴坦的抗菌药物敏感率稍高于未复发组;11.10 mmol/L葡萄糖可促进生物膜的形成,15.00μg/mL壳聚糖季铵盐对生物膜的形成有一定抑制作用.结论 引起耳道感染的铜绿假单胞菌生物膜形成能力较强,生物膜的形成与疾病复发有一定的关系;降低血糖水平及使用壳聚糖季铵盐凝胶对抑制生物膜形成有一定的作用.

Background: Few data are available on the risk factors involved in nosocomial meningitis from multi-drug-resistant Gram-negative bacteria (MDR-GNB). Our aim was to identify the risk factors of prognosis for MDR-GNB nosocomial meningitis.Methods: Retrospective study of patients undergoing neurosurgery and with positive cerebrospinal fluid culture results post operation between January 2012 and January 2017 in a tertiary hospital in China.Results: In total, 3533 patients were screened. Forty patients with meningitis and completed data were included and divided into two groups, 29 who survived in the successful group (SG) and 11 who died in the failed group (FG). Statistically significant different factors involved in treating successful and failed were pathogen types, highest body temperature in the first 24h of symptoms, CSF glucose content and meropenem susceptibility (for Acinetobacter baumannii). The most common pathogen in the failed ones is Acinetobacter baumannii with meropenem MIC ≥ 16mg/L.Conclusions: Treatment of MDR-GNB nosocomial meningitis is more likely to fail in patients with severe condition when symptoms occur and infected by Acinetobacter baumannii. Researches with larger population are needed to find more factors to improve patient outcome.

Background/purpose: As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. Methods: An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. Results: Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. Conclusions: The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services. Copyright (C) 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.

目的 回顾性分析2010-2014年中国侵袭性真菌耐药监测网(CHIF-NET) 62所监测中心重症监护室(ICU)侵袭性酵母的现状,了解我国侵袭性酵母分布的特征及其对唑类药物的耐药情况.方法 收集各所监测中心初步鉴定的菌株,送至北京协和医院检验科,采用基质辅助激光解吸电离飞行时间质谱技术结合分子测序技术对所有菌株进行复核鉴定,再进行唑类药物敏感性检测.结果 2010-2014年,62所监测中心ICU共检出侵袭性酵母2 863株,其中以念珠菌属最多,计2 771株.标本类型包括血液标本(50.8％,1 453/2863),无菌体液标本(49.2％,1 410/2863);其中,50.7％(1 404/2 771)的念珠菌属分离自血液标本.5年间,白念珠菌对氟康唑和伏立康唑十分敏感,敏感率＞99.0％;热带念珠菌对氟康唑和伏立康唑的耐药率显著升高,均从12.2％升至23.1％(P＜0.01);光滑念珠菌对氟康唑的耐药率也显著升高,从14.7％升至27.7％ (P＜0.01).非念珠菌属中,新型隐球菌复合体对伏立康唑全部敏感,从2013年开始出现对氟康唑耐药菌;其他酵母对两种唑类药物耐药率整体较高,分别为43.6％和32.7％.菌株复核鉴定的正确率为86.2％(2 467/2 863).结论 ICU中侵袭性酵母分离株中以念珠菌属为主,主要分离自血液,氟康唑和伏立康唑对其抗菌作用非常显著;而非白念珠菌的耐药率有不同程度的升高及交叉耐药的出现,临床需要加以重视.

[目的]探讨利多卡因对细菌培养结果的影响,为临床关节假体周围感染(periprosthetic joint infection,PJI)提高细菌培养阳性率提供理论依据.[方法]制备8种标准菌株,包括金黄色葡萄球菌、表皮葡萄球菌、人葡萄球菌、大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌、化脓链球菌和白色念珠菌的菌悬液(3×106CFU/ml),模拟临床PJI的关节滑液.各标准菌株的菌悬液分为两组,利多卡因组为2％利多卡因100 μ1+菌悬液600μl,盐水组为0.45％无菌生理盐水100 μl+菌悬液600μl,混匀1 min后,分别接种于5个琼脂平板培养基上进行24h定量培养,通过菌落计数比较两组培养基上的细菌生长情况.[结果] 24h定量细菌培养结果表明,利多卡因组金黄色葡萄球菌、表皮葡萄球菌、人葡萄球菌、大肠杆菌、肺炎克雷伯杆菌、鲍曼不动杆菌、白色念珠菌菌株的菌落计数显著低于盐水组,差异均有统计学意义(P＜0.05),而两组间化脓链球菌菌株的菌落计数差异无统计学意义(P＞0.05).[结论]2％利多卡因注射液对临床中常见的PJI病原菌具有很强的抗菌作用.因此,在关节液取样前使用2％利多卡因注射液进行局部浸润麻醉可能影响细菌培养结果.

基质辅助激光解吸电离飞行时间质谱(Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,MALDI-TOF MS)技术,简称飞行质谱技术,是近年来临床微生物鉴定领域最具代表性的技术之一.每种微生物都由自身独特的肽/蛋白质组成,通过MALDI-TOF MS检测微生物的肽/蛋白质指纹图谱,经软件处理并与微生物数据库进行比对分析,可在几分钟之内完成对微生物种、属水平的鉴定[1-2].与传统的检测微生物表型和生理生化方法相比,MALDI-TOF MS具有快速、准确、高通量、和低成本的优势[3-4].除了可鉴定常见细菌和酵母样真菌[5],更极大提高了临床微生物实验室对苛养菌、厌氧菌、丝状真菌以及分枝杆菌等难鉴定微生物的鉴定效率和能力[6-12].对MALDI-TOF MS系统开发耐药性分析、细菌同源性分析及阳性血培养、无菌体液细菌直接鉴定等工作尚处在科研阶段[13-19] ,随着研究的成熟和标准化的实现,有望逐步从研究走入临床应用.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates that carry mecA but are oxacillin susceptible (OS-MRSA; oxacillin minimum inhibitory concentration [MIC] ≤2 μg/mL) are increasingly reported worldwide in the past decade. In this study, an OS-MRSA isolate FC1102921 from an imported meat sample was characterized and the oxacillin resistance mutation frequency and mutant prevention concentration (MPC) to oxacillin was determined. Isolate FC1102921 was pvl negative and contained SCCmec V (5C2&5), the sequence type and spa type were identified as ST398-t034. The MPCs of isolate FC1102921 to oxacillin was 16 μg/mL. The resistance mutation frequency of isolate FC1102921 to oxacillin was 0.036%. The expression of mecA in isolate FC1102921 was detectable, but the mecA expression in the mutant isolate FC1102921m increased 13.8-folds. Our data indicated that S. aureus FC1102921 was not a hypermutator, and the high-resistance mutation frequency of S. aureus FC1102921 was specific to oxacillin and penicillin. SCCmec V region of isolate FC1102921 and FC1102921m was identical, functional blaI and blaR1 were identified in SCCmec region of both isolates, and no plasmid loss was identified in mutant isolate FC1102921m. To the best of our knowledge, this is the first report of the resistance mutation frequency and MPC study of an OS-MRSA ST398-t034 isolate. The high oxacillin MPC value and high oxacillin resistance mutation frequency was not related to a curable plasmid as previously reported, which further highlighted that an in-depth study should be carried out to clarify the mechanism and role of the OS-MRSA isolates in the emergence and transmission of MRSA ST398-t034.

目的 利用GeneXpert Carba-R(R)全自动病原体快速检测系统检测碳青霉烯类耐药肠杆菌科细菌的耐药基因,了解该院耐碳青霉烯类肠杆菌科细菌(CRE)耐药情况和耐药基因分布,为了解临床CRE感染趋势提供依据.方法 采用回顾性调查方法,收集2016年3月至2017年10月分离自非呼吸道标本的141株耐碳青霉烯类肠杆菌科菌株.结果 肺炎克雷伯杆菌114株,大肠埃希菌13株,阴沟肠杆菌8株,产气肠杆菌2株,弗氏枸橼酸杆菌3株,魏氏柠檬酸杆菌1株.blaKPC 103株,blaNDM 22株,blaoxA-485株,含两种及两种以上耐药基因12株.结论 GeneXpert Carba-R(R)全自动病原体快速检测系统能快速检测出耐碳青霉烯类肠杆菌的耐药基因,耐碳青霉烯类抗菌药物的细菌对多种抗菌药物同时耐药,检出的耐药基因型为KPC、NDM、OXA-48及IMP.含不同耐药基因的肠杆菌科细菌其耐药情况不同.

近年来侵袭性真菌感染呈持续增多趋势,准确、早期诊断是治疗疾病的关键.然而,目前我国临床实验室真菌检测能力离临床诊治需求尚有较大差距,亟待改进.

自20世纪80年代末开始,基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption ionization time-of-flightmass spectrometry, MALDI-TOF MS)技术以其对微生物种属鉴定的快速、准确、低成本优势,逐步在临床微生物鉴定领域得到广泛认可.该技术对微生物鉴定的理论基础是将设备采集的未知样品图谱与数据库中已知菌种的图谱进行统计学聚类分析,获得鉴定结果,故此菌种鉴定准确性和特异性高度依赖于MALDI-TOF MS生产厂商或用户预先建立的微生物MALDI-TOF MS图谱数据库的完善性与可靠性.

Objectives: The aim of this study was to perform a detailed genomic characterisation of IncR plasmids from China. Methods: Three IncR plasmids (p13190-tetA, p02085-tetA and p30860-tetA) from clinical isolates of Klebsiella pneumoniae, Citrobacter freundii and Enterobacter cloacae, respectively, were fully sequenced using high-throughput genome sequencing and were compared with five previously sequenced IncR plasmids (pHN84KPC, pSH-01, pK245, pKPC_P16 and pKPC-LK30) from China. Results: The eight IncR plasmids from China possessed conserved IncR backbones composed of repB, parAB, umuCD, retA and resD. Resistance accessory modules integrated into the IncR backbones included multidrug resistance (MDR) regions in p30860-tetA, p02085-tetA, p13190-tetA and pK245, bla(KPC-2) regions in pHN84KPC, pKPC-LK30 and pKPC_P16, and the Delta Tn1721-sil region in pSH-01. These resistance accessory modules were inserted at a site between retA and vagD, resulting in loss of the backbone genes vagCD in some of the plasmids. The resistance accessory modules differed dramatically from one another and carried distinct profiles of resistance markers. In particular, all of p13190-tetA, p02085-tetA, p30860-tetA, pHN84KPC, pSH-01 and pK245 carried tetracycline resistance tet gene modules, and the carbapenemase gene bla(KPC-2) was identified in pHN84KPC, pKPC-LK30 and pKPC_P16. In addition, one or more regions responsible for plasmid replication and/or maintenance were found in some of the resistance accessory modules, facilitating stable replication of corresponding IncR plasmids at steady-state copy numbers. Conclusions: This detailed comparative genomics analysis of IncR plasmids from China provides a deeper insight into the diversification and evolution of IncR plasmids. (C) 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.