Evidence suggests that the spread of mcr-1 is from animals to human beings.1, 5 Thus, we did a retrospective study to examine the approximate time of emergence of the mcr-1 gene in food-producing ...animals.
Summary Background The mcr-1 gene confers transferable colistin resistance. mcr-1 -positive Enterobacteriaceae (MCRPE) have attracted substantial medical, media, and political attention; however, so ...far studies have not addressed their clinical impact. Herein, we report the prevalence of MCRPE in human infections and carriage, clinical associations of mcr-1 -positive Escherichia coli (MCRPEC) infection, and risk factors for MCRPEC carriage. Methods We undertook this study at two hospitals in Zhejiang and Guangdong, China. We did a retrospective cross-sectional assessment of prevalence of MCRPE infection from isolates of Gram-negative bacteria collected at the hospitals from 2007 to 2015 (prevalence study). We did a retrospective case-control study of risk factors for infection and mortality after infection, using all MCRPEC from infection isolates and a random sample of mcr-1 -negative E coli infections from the retrospective collection between 2012 and 2015 (infection study). We also did a prospective case-control study to assess risk factors for carriage of MCRPEC in rectal swabs from inpatients with MCRPEC and mcr-1 negative at the hospitals and collected between May and December, 2015, compared with mcr-1 -negative isolates from rectal swabs of inpatients (colonisation study). Strains were analysed for antibiotic resistance, plasmid typing, and transfer analysis, and strain relatedness. Findings We identified 21 621 non-duplicate isolates of Enterobacteriaceae, Acinetobacter spp, and Pseudomonas aeruginosa from 18 698 inpatients and 2923 healthy volunteers. Of 17 498 isolates associated with infection, mcr-1 was detected in 76 (1%) of 5332 E coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae , one (<1%) of 890 Enterobacter cloacae , and one (1%) of 162 Enterobacter aerogenes . For the infection study, we included 76 mcr-1 -positive clinical E coli isolates and 508 mcr-1 -negative isolates. Overall, MCRPEC infection was associated with male sex (209 41% vs 47 63%, adjusted p=0·011), immunosuppression (30 6% vs 11 15%, adjusted p=0·011), and antibiotic use, particularly carbapenems (45 9% vs 18 24%, adjusted p=0·002) and fluoroquinolones (95 19% vs 23 30%, adjusted p=0·017), before hospital admission. For the colonisation study, we screened 2923 rectal swabs from healthy volunteers, of which 19 were MCRPEC, and 1200 rectal swabs from patients, of which 35 were MCRPEC. Antibiotic use before hospital admission (p<0·0001) was associated with MCRPEC carriage in 35 patients compared with 378 patients with mcr-1-negative E coli colonisation, whereas living next to a farm was associated with mcr-1-negative E coli colonisation (p=0·03, univariate test). mcr-1 could be transferred between bacteria at high frequencies (10−1 to 10−3 ), and plasmid types and MCRPEC multi-locus sequence types (MLSTs) were more variable in Guangdong than in Zhejiang and included the human pathogen ST131. MCRPEC also included 17 unreported ST clades. Interpretation In 2017, colistin will be formally banned from animal feeds in China and switched to human therapy. Infection with MRCPEC is associated with sex, immunosuppression, and previous antibiotic exposure, while colonisation is also associated with antibiotic exposure. MLST and plasmid analysis shows that MCRPEC are diversely spread throughout China and pervasive in Chinese communities. Funding National Key Basic Research Program of China, National Natural Science Foundation of China/Zhejiang, National Key Research and Development Program, and MRC, UK.
SUMMARY Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which ...confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.
Summary
Colistin resistance has attracted substantial attention after colistin was considered as a last‐resort drug for the treatment of infections caused by carbapenem‐resistant and/or ...multidrug‐resistant (MDR) Gram‐negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.
Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a flavin-dependent monooxygenase that ...modifies tigecycline
. Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as bla
, resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.
•Up to 18% of 1-day-old chicks contaminated with blaNDM within 24 h in grow-out farm.•Novel NDM-like-metallo-β-lactamase gene, blaNLM was identified in Pseudomonas putida.•IncX3 plasmid account for ...71% of blaNDM carriage and persist in farm over 16 months.•Over 20% NDM-producing isolates carry either colistin resistance gene mcr-1 or mcr-8.•Long vacancy period and disinfection procedure fail to eliminate blaNDM in farm.
While carbapenem use is prohibited in the poultry production chain and carbapenem-resistant Enterobacteriaceae (CRE) are absent from hatchery farms, New Delhi metallo-β-lactamase-producing CRE contamination of commercial broiler chicken farms (grow-out farms) can occur via living hosts such as flies. However, it is not known whether the inanimate factors from in-house environment play a role in the persistence of CRE on commercial farms. Herein, we monitored one typical broiler house in Hebei Province, China, from January 2017 to April 2018. We collected 350 cloacal samples from four broiler batches along with 582 environmental samples (194 in the raising period and 388 in the vacancy period) from sites including the surfaces of drooping boards, feeding troughs, nipple drinkers, corridor floors, sewage trenches, and air. All samples were screened for blaNDM and cultured for NDM-producing isolates. The resistance profiles, genotypes, and genetic context of blaNDM in CRE isolates were further characterized. Results showed that 1-day-old broilers, which were transferred from a hatchery farm and negative for CRE, acquired blaNDM within 24 h of transfer (2 days of age), with a detection rate of up to 18.6%. High blaNDM detection rates (26.8%–31.4%) were obtained among all environmental samples except air after standard cleaning and disinfection during the vacancy period. blaNDM carriage rates (52.9%–72.9%) within the flocks remain stable and high across the next three broiler batches. Overall, 279 NDM-producing bacteria, including 259 Enterobacteriaceae (8 species), 14 Morganellaceae (3 species), three Alcaligenes faecalis and three Pseudomonas putida isolates, were recovered from 85 (24.3%) cloacal and 101 (17.4%) environmental samples. Three NDM variants, including NDM-5 (n = 181), NDM-1 (n = 92), and NDM-9 (n = 3), and a novel NDM-like-metallo-β-lactamase (NLM, n = 3) were identified among the samples. The predominant NDM-producing CRE species among the samples were Klebsiella pneumoniae (CRKP; 32.6%, n = 91) and Escherichia coli (CREC; 27.2%, n = 76). Both clonal and horizontal transmission of blaNDM and an overlap of sequence types (STs) were observed in both CREC and CRKP from chicken and environmental samples. Notably, ST6751 CREC and ST37 CRKP persisted throughout the 16-month surveillance period. IncX3 (n = 197, 7 species), IncA/C2 (n = 41, 5 species), and IncFII (n = 8, E. coli) were the three major blaNDM-carrying plasmid types among the isolates. Although routine cleaning and disinfection procedures and “all-in/all-out” management were performed, once introduced to the farm environment, a diverse range of NDM-positive isolates may survive and persist, becoming an important reservoir of NDM-positive CRE for broiler chickens. Therefore, cleaning and disinfection procedures should be improved on poultry farms to avoid cross-contamination of NDM-producing bacteria between different batches of chickens, as well as further downstream in the poultry production chain.
This study was conducted to determine the prevalence and distribution of Campylobacter species along a broiler production chain from farm to retail, and to evaluate the antimicrobial resistance ...profile of Campylobacter isolates. A total of 259 Campylobacter isolates (C. jejuni n=106, C. coli n=153) were isolated from broiler ceca samples (72.5%, 103/142), broiler carcasses (34.1%, 46/135), and retail broiler meat (31.3%, 40/128) samples collected in Shanghai, China. Minimal inhibitory concentrations of six antimicrobials were determined using the agar dilution method. High prevalence of resistance to ciprofloxacin (C. jejuni: 99.1%;C. coli: 100%) and tetracycline (C. jejuni: 100%;C. coli: 98.7%) was detected among the C. jejuni and C. coli isolates. The vast majority of C. coli were resistant to clindamycin (92.2%), gentamicin (95.4%), and erythromycin (94.1%), but only 25.5%, 53.8%, and 16.0% of C. jejuni exhibited resistance to these three antimicrobials, respectively. In contrast, the prevalence of florfenicol resistance in C. jejuni (37.7%) was significantly higher than that in C. coli (7.8%) (P<0.05). It is noteworthy that all Campylobacter isolates were resistant to one or more antimicrobials, and 71.7% of C. jejuni and 98.0% of C. coli isolates exhibited multi-drug resistance (resistant to three or more antimicrobials). Fifty-five C. jejuni and sixty C. coli isolates, selected from different production stages, species, and antimicrobial resistance patterns, were analyzed by pulsed field gel electrophoresis (PFGE), among which 15 unique PFGE patterns (PFGE patterns represented by a single strain) and 31 clusters (PFGE patterns represented by multiple strains) were detected. Furthermore, nearly all of the PFGE patterns of the Campylobacter strains isolated from retail broiler meats overlapped with those of the strains from ceca and slaughterhouse carcasses. Together, these findings revealed the high prevalence of Campylobacter species in a broiler chicken production chain, and the concerning situation of antimicrobial resistance in Campylobacter species. The findings also indicated that Campylobacter isolates from retail broiler meats were associated with fecal contamination in the slaughterhouse, underlying the need for improved measures for reducing carcass contamination in slaughter plants.
•First tracking Campylobacter contamination in broiler production chain in China.•Provided evidence suggesting C. coli has become the predominant species in China.•Most (83.4%) of Campylobacter strains exhibited multi-drug resistance.•Campylobacter in retail meat was originated from fecal contamination in abattoir.
This study aimed to analyze the prevalence of Salmonella isolated from different parts of the food production chain, and to characterize these isolates. A total of 165 Salmonella enterica isolates ...were identified from 1382 samples taken from conventional farms, abattoirs and retail markets from 2010 to 2011 in Sichuan, China. The Salmonella isolates were assayed for serotype, antimicrobial susceptibility, prevalence of class 1 integrons and β-lactamase genes, and subtyped using pulsed-field gel electrophoresis. Among these isolates, S. enterica serotypes Derby (76 isolates, 46%) and Typhimurium (16 isolates, 10%) were the most prevalent, and high antimicrobial resistance rates were observed for tetracycline (77%), sulfamethoxazole/trimethoprim (43%), nalidixic acid (41%) and spectinomycin (41%). Class 1 integrons were detected in 21% of these isolates, and contained gene cassettes dfrA12–aadA2, dfrA1–aadA1, dfrA1, blaPSE-1 and dfrA1/aadA2. blaOXA-1 was the most commonly identified β-lactamase gene (n=14), followed by blaTEM-1 (n=6), blaPSE-1 (n=4) and blaCMY-2 (n=1). A S. enterica serotype Indiana isolate derived from chicken from a market was positive for both blaOXA-1 and blaCMY-2, and resistant to nine tested antibiotics. The PFGE patterns were diverse. Our findings indicated that most isolates from different sampling sites were phenotypically and genetically diverse, and Salmonella was widespread and may transmit along the food production chain from farm to market. Isolates with decreased susceptibility to fluoroquinolones and extended-spectrum cephalosporins, which are used to fight foodborne Salmonella, pose a serious threat to public health.
► The resistance of Salmonella to ten antimicrobial agents was detected. ► S. Derby (46%) and S. Typhimurium (10%) were the main serotypes identified. ► Class 1 integrons were detected in 34 Salmonella isolates. ► Coexistence of blaOXA-1 and blaCMY-2 in S. Indiana was reported in Sichuan.
Plasmid-mediated, transmissible, tigecycline-inactivating enzyme Tet(X) has attracted considerable public attention. However, so far studies have not addressed its impact on public health and the ...ecosystem. Herein, we report the prevalence and molecular epidemiology of tet(X)-positive bacteria (TPB) from diverse sources, investigate the host-specificity of TPB and the transferability of tet(X). Sample collection was conducted between 2018 and 2020 in 30 provinces in China. PCR screening suggested tet(X) was prevalent among freshwater fishes (24.7%, 95% CI 19.4–30.7%), followed by chickens (23.6%, 21.2–26.2%), cattle (19.3%, 16.4–22.5%), healthy individuals (6.2%, 5.4–7.1%), and patients (0.3%, 0.0–1.1%). Soil and freshwater samples all tested negative for tet(X). A total of 289 TPB were isolated from 7516 samples (120/1181 chicken, 82/669 cattle, 68/3229 healthy individual, 17/239 freshwater fish and 2/2121 clinical samples). TPB distributed in six major families of bacteria including Moraxellaceae (n = 99, 34.3%), Flavobacteriaceae (n = 95, 32.9%), Enterobacteriaceae (n = 83, 28.7%), Pseudomonadaceae (n = 9, 3.1%), Sphingobacteriaceae (n = 2, 0.7%) and unclassified Gammaproteobacteria (n = 1, 0.3%). Diverse tet(X) genes including tet(X2), tet(X3), tet(X4), tet(X5) and tet(X6) were identified from different TPB. The tet(X)-positive bacteria were highly diverse, with ST10 complex belonging to the dominant E. coli clone. Novel hosts of tet(X) including Enterobacter hormaechei, Ignatzschineria indica and Oblitimonas alkaliphila were identified. Isolates from different families exhibited different antimicrobial resistance profiles. Co-existence of tet(X) with other resistance genes such as floR (66.8%) and carbapenemase genes (33.2%) was commonly observed. tet(X) could be transferred among E. coli isolates at frequencies from 10−4 to 10−10. Species other than E. coli failed to transfer tet(X) gene to the E. coli recipient via conjugation. Discriminant analysis of principal components analysis suggested inter-host transmission of tet(X)-positive E. coli among diverse hosts was not observed. Future studies are needed to monitor the transmission trend as well as the impact of this resistance gene in clinical infection control.
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•We present the first and most comprehensive nationwide surveillance of tet(X)-positive bacteria in China•tet(X)-positive bacteria was more prevalent in fishes, chickens, and cattle than in healthy individuals and patients•tet(X) genes distributed among Proteobacteria and Bacteroidetes•tet(X)-positive bacteria were highly diverse and multidrug resistant•Inter-host transmission of tet(X)-positive E. coli among diverse hosts was not observed
•We detected an average nasal carriage rate of 11.2% of MRSA in pigs in China.•ST9-t899 was the predominant type of porcine LA-MRSA isolates in China.•All porcine LA-MRSA showed resistance to a wide ...range of antibiotics.•The multi-resistance gene lsa(E) was common among porcine LA-MRSA in China.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have been reported in various countries worldwide. However, although China is one of the biggest pig and pork producers, large-scale studies on pig-associated LA-MRSA from China are scarce. The aims of this study were to analyze 2420 non-duplicate samples collected from pigs at swine farms and slaughterhouses in different regions in China during 2014 for the prevalence of pig-associated MRSA and to determine the antimicrobial resistance pheno- and genotypes of the respective isolates. MRSA isolates were identified in 270 (11.2%) samples. The isolates were characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST), spa typing, pulsed-field gel electrophoresis (PFGE) and screening for resistance genes. All MRSA isolates belonged to the clonal complex 9 and spa type t899, but showed variable PFGE patterns. All isolates were non-susceptible to oxacillin, cefoxitin, clindamycin, chloramphenicol, florfenicol, ciprofloxacin, and valnemulin. High rates of resistance were also observed for tetracycline (99.6%), erythromycin (97.0%), quinupristin-dalfopristin (97.0%), and gentamicin (80.4%). Three linezolid-non-susceptible isolates containing the multi-resistance gene cfr and nine rifampicin-non-susceptible isolates with mutations in rpoB were detected. Resistance to β-lactams was exclusively associated with mecA, while phenicol resistance was mainly attributable to fexA, except in the three cfr-positive isolates. The pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) was identified in all MRSA isolates, and no other pleuromutilin resistance genes, except cfr in three isolates, were detected. Pigs are the most important hosts of LA-MRSA in China. Screening for pig-associated MRSA is necessary to monitor changes in epidemiology and characteristics of these important pathogens.
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