Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and blaOXA-48 isolated at a paediatric hospital in Vietnam

Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and blaOXA-48 isolated at... Sir, Carbapenem resistance among the nosocomial pathogen Klebsiella pneumoniae is increasing worldwide, increasing morbidity, mortality and healthcare costs.1 Colistin is the drug of choice for treating infections caused by carbapenem-resistant K. pneumoniae (CR-KP); however, its usefulness is threatened by the dissemination of the colistin resistance gene mcr-1.2 Although clinical isolates of K. pneumoniae with mcr-1 have been sporadically reported, the gene still appears to be relatively rare among the species,2–4 particularly among CR-KP, and chromosomally mediated resistance appears to be the most common resistance mechanism. Le et al.5 reported that nosocomial infection prevalence in ICUs at three Vietnamese paediatric hospitals was 33%, mostly caused by K. pneumoniae. The CR-KP rate was 55%. To evaluate the prevalence and characteristics of mcr-1-carrying isolates of CR-KP, we collected 205 clinical isolates of CR-KP [determined using the VITEK 2 system (bioMérieux, Marcy-l’Étoile, France)] from February 2015 to September 2016 from 205 patients at one of these hospitals. The isolates were screened for mcr-1 with real-time PCR2 and three (1.5%) were positive. Two isolates were from tracheal fluid of patients with respiratory failure on the neonatal ICU (taken approximately 4 months apart) and one isolate was from blood of a patient with bronchopneumonia on the ICU (Table 1). With the available data, no conclusions on epidemiological links between the patients could be determined. Table 1 Characteristics of three isolates of K. pneumoniae with the mcr-1 gene isolated at a Vietnamese paediatric hospital   Isolate VN806TZ  Isolate VNX08co4  Isolate VN734eta  Diagnosis  respiratory failure  respiratory failure  bronchopneumonia  Date of culture (year-month-day)  2015-12-10  2016-04-05  2016-05-09  Ward  neonatal ICU  neonatal ICU  ICU  Specimen  tracheal fluid  tracheal fluid  blood  Antibiotic resistance genes  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M)      MIC (mg/L)  SIR  MIC (mg/L)  SIR  MIC (mg/L)  SIR    Colistin  8  R  4  R  4  R  Amikacin  2  S  0.5  S  1  S  Gentamicin  24  R  6  R  16  R  Tobramycin  32  R  8  R  24  R  Cefotaxime  >256  R  >256  R  192  R  Ceftazidime  24  R  12  R  8  R  Amoxicillin/clavulanic acid  >256  R  >256  R  >256  R  Piperacillin/tazobactam  >256  R  >256  R  >256  R  Ceftazidime/avibactam  0.5  S  0.75  S  0.5  S  Meropenem  >32  R  >32  R  >32  R  Chloramphenicol  >256  R  >256  R  >256  R  Fosfomycin  >1024  R  >1024  R  >1024  R  Ciprofloxacin  0.5  I  0.75  R  0.38  I  Trimethoprim/ sulfamethoxazole  >32  R  >32  R  0.5  S  Tigecycline  0.38  S  1  S  0.75  S    Isolate VN806TZ  Isolate VNX08co4  Isolate VN734eta  Diagnosis  respiratory failure  respiratory failure  bronchopneumonia  Date of culture (year-month-day)  2015-12-10  2016-04-05  2016-05-09  Ward  neonatal ICU  neonatal ICU  ICU  Specimen  tracheal fluid  tracheal fluid  blood  Antibiotic resistance genes  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M)      MIC (mg/L)  SIR  MIC (mg/L)  SIR  MIC (mg/L)  SIR    Colistin  8  R  4  R  4  R  Amikacin  2  S  0.5  S  1  S  Gentamicin  24  R  6  R  16  R  Tobramycin  32  R  8  R  24  R  Cefotaxime  >256  R  >256  R  192  R  Ceftazidime  24  R  12  R  8  R  Amoxicillin/clavulanic acid  >256  R  >256  R  >256  R  Piperacillin/tazobactam  >256  R  >256  R  >256  R  Ceftazidime/avibactam  0.5  S  0.75  S  0.5  S  Meropenem  >32  R  >32  R  >32  R  Chloramphenicol  >256  R  >256  R  >256  R  Fosfomycin  >1024  R  >1024  R  >1024  R  Ciprofloxacin  0.5  I  0.75  R  0.38  I  Trimethoprim/ sulfamethoxazole  >32  R  >32  R  0.5  S  Tigecycline  0.38  S  1  S  0.75  S  S, susceptible; I, intermediately resistant; R, resistant. mcr-1-positive isolates were whole-genome sequenced using the Illumina MiSeq platform (Illumina, San Diego, CA, USA) and reads were uploaded to the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra, accession no. SRR5799030-SRR5799032). Average read length was 248 bp and average sequencing depth was 90×. Assembly was performed with SPAdes v.3.1.1 and CLC Genomics Workbench v.9.5.3 (QIAGEN, Hilden, Germany). Antibiotic resistance genes and plasmid associations were queried using the databases at the Center for Genomic Epidemiology (http://www.genomicepidemiology.org/). In addition to mcr-1, the isolates carried a number of resistance genes (Table 1) including aminoglycoside, quinolone, fosfomycin, macrolide, phenicol, sulphonamide and trimethoprim resistance genes, as well as the carbapenemase gene blaOXA-48 carried on the highly transmissible plasmid pOXA-48.6 For the isolates, mcr-1 was found on 145 307, 188 383 and 189 030 nt long contigs. The contigs had ≥99% nt similarity to the IncHI2 MDR plasmid pHNSHP45-2 (NCBI accession no. KU341381), which has previously been reported to carry mcr-1 in Escherichia coli.7,mcr-1 has previously been reported to be carried on IncP plasmids8 and IncX4 plasmids4 in K. pneumoniae, indicating that dissemination of mcr-1 among K. pneumoniae is occurring via many different plasmids. An approximately 3688 nt long segment containing ISApl1, mcr-1 and a putative ORF was located approximately 27 400 nt downstream of the location in the plasmid reference sequence, in an inverted orientation (Figure S1, available as Supplementary data at JAC Online). This segment, with an additional downstream ISApl1 element, constitutes a composite transposon, hypothesized to be important in mcr-1 mobilization, and the loss of the downstream ISApl1 element may stabilize mcr-1 on the plasmid, facilitating dissemination of the gene.9 To determine chromosomal colistin resistance determinants, sequences of pmrA, pmrB, pmrC, pmrD, phoP, phoQ, crrA, crrB and mgrB were extracted from the WGS data and evaluated using PROVEAN (http://provean.jcvi.org/index.php). No mutations that were predicted to alter the function of the gene product were detected. MLST and SNP analysis were performed with CLC Genomics Workbench to evaluate the phylogenetic relationship of the isolates. All isolates were ST307 and the SNP analysis (core genome size: 5 166 857 bp) indicated a close relationship (maximum difference of 22 SNPs), indicating the possibility of the isolates constituting a single clone. Hypervirulence was assessed using string tests10 and querying the BIGSdb database (http://bigsdb.pasteur.fr/) for virulence genes and capsular serotyping. The string tests were negative, genes encoding type 3 fimbriae were the only virulence genes found and the K serotype was ‘not defined’, indicating that the isolates were not hypervirulent. MIC determination (Table 1) was performed using Etests (bioMérieux), although MICs of colistin were determined with broth microdilution. Clinical breakpoints were used according to EUCAST (v. 7.1). The isolates were resistant to colistin (MICs between 4 and 8 mg/L) and meropenem (MIC >32 mg/L). The isolates were susceptible only to amikacin, tigecycline and ceftazidime/avibactam, except VN734eta, which was also susceptible to trimethoprim/sulfamethoxazole. The finding of clinical isolates of K. pneumoniae harbouring both mcr-1 and blaOXA-48 in a healthcare setting with high rates of nosocomial infections is troubling and emphasizes the need for improved hospital hygiene and prudent use of colistin and carbapenems to prevent further dissemination and emergence of the still rare occurrence of mcr-1 in CR-KP. Ethics approval Ethics approval for this study was granted by the Ethics Committee at the National Hospital of Pediatrics (reference no. VNCH-RICH-16-014). Funding This work was supported financially by Linköping University, the Karolinska Institute, the Training and Research Academic Collaboration (TRAC) – Sweden-Vietnam, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), ReAct and the Swedish Research Council. Transparency declarations None to declare. Supplementary data Figure S1 is available as Supplementary data at JAC Online. References 1 Lee CR, Lee JH, Park KS et al.   Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol  2016; 7: 895. Google Scholar PubMed  2 Liu YY, Wang Y, Walsh TR et al.   Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis  2016; 16: 161– 8. Google Scholar CrossRef Search ADS PubMed  3 Rolain JM, Kempf M, Leangapichart T et al.   Plasmid-mediated mcr-1 gene in colistin-resistant clinical isolates of Klebsiella pneumoniae in France and Laos. Antimicrob Agents Chemother  2016; 60: 6994– 5. Google Scholar CrossRef Search ADS PubMed  4 Tian GB, Doi Y, Shen J et al.   MCR-1-producing Klebsiella pneumoniae outbreak in China. Lancet Infect Dis  2017; 17: 577. Google Scholar CrossRef Search ADS PubMed  5 Le NK, Hf W, Vu PD et al.   High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: a multi-centre point prevalence survey. Medicine (Baltimore)  2016; 95: e4099. Google Scholar CrossRef Search ADS PubMed  6 Poirel L, Bonnin RA, Nordmann P. Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. Antimicrob Agents Chemother  2012; 56: 559– 62. Google Scholar CrossRef Search ADS PubMed  7 Zhi C, Lv L, Yu LF et al.   Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis  2016; 16: 292– 3. Google Scholar CrossRef Search ADS PubMed  8 Zhao F, Feng Y, Lü X et al.   IncP plasmid carrying colistin resistance gene mcr-1 in Klebsiella pneumoniae from hospital sewage. Antimicrob Agents Chemother  2017; 61: e02229-16. Google Scholar PubMed  9 Snesrud E, He S, Chandler M et al.   A model for transposition of the colistin resistance gene mcr-1 by ISApl1. Antimicrob Agents Chemother  2016; 60: 6973– 6. Google Scholar CrossRef Search ADS PubMed  10 Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence  2013; 4: 107– 18. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and blaOXA-48 isolated at a paediatric hospital in Vietnam

Loading next page...
 
/lp/ou_press/colistin-and-carbapenem-resistant-klebsiella-pneumoniae-carrying-mcr-1-v3SAEQ4P21
Publisher
Oxford University Press
ISSN
0305-7453
eISSN
1460-2091
D.O.I.
10.1093/jac/dkx491
Publisher site
See Article on Publisher Site

Abstract

Sir, Carbapenem resistance among the nosocomial pathogen Klebsiella pneumoniae is increasing worldwide, increasing morbidity, mortality and healthcare costs.1 Colistin is the drug of choice for treating infections caused by carbapenem-resistant K. pneumoniae (CR-KP); however, its usefulness is threatened by the dissemination of the colistin resistance gene mcr-1.2 Although clinical isolates of K. pneumoniae with mcr-1 have been sporadically reported, the gene still appears to be relatively rare among the species,2–4 particularly among CR-KP, and chromosomally mediated resistance appears to be the most common resistance mechanism. Le et al.5 reported that nosocomial infection prevalence in ICUs at three Vietnamese paediatric hospitals was 33%, mostly caused by K. pneumoniae. The CR-KP rate was 55%. To evaluate the prevalence and characteristics of mcr-1-carrying isolates of CR-KP, we collected 205 clinical isolates of CR-KP [determined using the VITEK 2 system (bioMérieux, Marcy-l’Étoile, France)] from February 2015 to September 2016 from 205 patients at one of these hospitals. The isolates were screened for mcr-1 with real-time PCR2 and three (1.5%) were positive. Two isolates were from tracheal fluid of patients with respiratory failure on the neonatal ICU (taken approximately 4 months apart) and one isolate was from blood of a patient with bronchopneumonia on the ICU (Table 1). With the available data, no conclusions on epidemiological links between the patients could be determined. Table 1 Characteristics of three isolates of K. pneumoniae with the mcr-1 gene isolated at a Vietnamese paediatric hospital   Isolate VN806TZ  Isolate VNX08co4  Isolate VN734eta  Diagnosis  respiratory failure  respiratory failure  bronchopneumonia  Date of culture (year-month-day)  2015-12-10  2016-04-05  2016-05-09  Ward  neonatal ICU  neonatal ICU  ICU  Specimen  tracheal fluid  tracheal fluid  blood  Antibiotic resistance genes  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M)      MIC (mg/L)  SIR  MIC (mg/L)  SIR  MIC (mg/L)  SIR    Colistin  8  R  4  R  4  R  Amikacin  2  S  0.5  S  1  S  Gentamicin  24  R  6  R  16  R  Tobramycin  32  R  8  R  24  R  Cefotaxime  >256  R  >256  R  192  R  Ceftazidime  24  R  12  R  8  R  Amoxicillin/clavulanic acid  >256  R  >256  R  >256  R  Piperacillin/tazobactam  >256  R  >256  R  >256  R  Ceftazidime/avibactam  0.5  S  0.75  S  0.5  S  Meropenem  >32  R  >32  R  >32  R  Chloramphenicol  >256  R  >256  R  >256  R  Fosfomycin  >1024  R  >1024  R  >1024  R  Ciprofloxacin  0.5  I  0.75  R  0.38  I  Trimethoprim/ sulfamethoxazole  >32  R  >32  R  0.5  S  Tigecycline  0.38  S  1  S  0.75  S    Isolate VN806TZ  Isolate VNX08co4  Isolate VN734eta  Diagnosis  respiratory failure  respiratory failure  bronchopneumonia  Date of culture (year-month-day)  2015-12-10  2016-04-05  2016-05-09  Ward  neonatal ICU  neonatal ICU  ICU  Specimen  tracheal fluid  tracheal fluid  blood  Antibiotic resistance genes  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M), dfrA5  mcr-1, aac(3)-IId, aac(3)-IVa, aph(3')-Ia, aph(4)-Ia, aadA1, aadA2, blaDHA-1, blaOXA-48, blaCTX-M-14, blaTEM-1B, blaSHV-12, blaSHV-28, oqxA, oqxB, qnrB4, fosA, mph(A), floR, cmlA1, sul1, sul2, sul3, tet(M)      MIC (mg/L)  SIR  MIC (mg/L)  SIR  MIC (mg/L)  SIR    Colistin  8  R  4  R  4  R  Amikacin  2  S  0.5  S  1  S  Gentamicin  24  R  6  R  16  R  Tobramycin  32  R  8  R  24  R  Cefotaxime  >256  R  >256  R  192  R  Ceftazidime  24  R  12  R  8  R  Amoxicillin/clavulanic acid  >256  R  >256  R  >256  R  Piperacillin/tazobactam  >256  R  >256  R  >256  R  Ceftazidime/avibactam  0.5  S  0.75  S  0.5  S  Meropenem  >32  R  >32  R  >32  R  Chloramphenicol  >256  R  >256  R  >256  R  Fosfomycin  >1024  R  >1024  R  >1024  R  Ciprofloxacin  0.5  I  0.75  R  0.38  I  Trimethoprim/ sulfamethoxazole  >32  R  >32  R  0.5  S  Tigecycline  0.38  S  1  S  0.75  S  S, susceptible; I, intermediately resistant; R, resistant. mcr-1-positive isolates were whole-genome sequenced using the Illumina MiSeq platform (Illumina, San Diego, CA, USA) and reads were uploaded to the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra, accession no. SRR5799030-SRR5799032). Average read length was 248 bp and average sequencing depth was 90×. Assembly was performed with SPAdes v.3.1.1 and CLC Genomics Workbench v.9.5.3 (QIAGEN, Hilden, Germany). Antibiotic resistance genes and plasmid associations were queried using the databases at the Center for Genomic Epidemiology (http://www.genomicepidemiology.org/). In addition to mcr-1, the isolates carried a number of resistance genes (Table 1) including aminoglycoside, quinolone, fosfomycin, macrolide, phenicol, sulphonamide and trimethoprim resistance genes, as well as the carbapenemase gene blaOXA-48 carried on the highly transmissible plasmid pOXA-48.6 For the isolates, mcr-1 was found on 145 307, 188 383 and 189 030 nt long contigs. The contigs had ≥99% nt similarity to the IncHI2 MDR plasmid pHNSHP45-2 (NCBI accession no. KU341381), which has previously been reported to carry mcr-1 in Escherichia coli.7,mcr-1 has previously been reported to be carried on IncP plasmids8 and IncX4 plasmids4 in K. pneumoniae, indicating that dissemination of mcr-1 among K. pneumoniae is occurring via many different plasmids. An approximately 3688 nt long segment containing ISApl1, mcr-1 and a putative ORF was located approximately 27 400 nt downstream of the location in the plasmid reference sequence, in an inverted orientation (Figure S1, available as Supplementary data at JAC Online). This segment, with an additional downstream ISApl1 element, constitutes a composite transposon, hypothesized to be important in mcr-1 mobilization, and the loss of the downstream ISApl1 element may stabilize mcr-1 on the plasmid, facilitating dissemination of the gene.9 To determine chromosomal colistin resistance determinants, sequences of pmrA, pmrB, pmrC, pmrD, phoP, phoQ, crrA, crrB and mgrB were extracted from the WGS data and evaluated using PROVEAN (http://provean.jcvi.org/index.php). No mutations that were predicted to alter the function of the gene product were detected. MLST and SNP analysis were performed with CLC Genomics Workbench to evaluate the phylogenetic relationship of the isolates. All isolates were ST307 and the SNP analysis (core genome size: 5 166 857 bp) indicated a close relationship (maximum difference of 22 SNPs), indicating the possibility of the isolates constituting a single clone. Hypervirulence was assessed using string tests10 and querying the BIGSdb database (http://bigsdb.pasteur.fr/) for virulence genes and capsular serotyping. The string tests were negative, genes encoding type 3 fimbriae were the only virulence genes found and the K serotype was ‘not defined’, indicating that the isolates were not hypervirulent. MIC determination (Table 1) was performed using Etests (bioMérieux), although MICs of colistin were determined with broth microdilution. Clinical breakpoints were used according to EUCAST (v. 7.1). The isolates were resistant to colistin (MICs between 4 and 8 mg/L) and meropenem (MIC >32 mg/L). The isolates were susceptible only to amikacin, tigecycline and ceftazidime/avibactam, except VN734eta, which was also susceptible to trimethoprim/sulfamethoxazole. The finding of clinical isolates of K. pneumoniae harbouring both mcr-1 and blaOXA-48 in a healthcare setting with high rates of nosocomial infections is troubling and emphasizes the need for improved hospital hygiene and prudent use of colistin and carbapenems to prevent further dissemination and emergence of the still rare occurrence of mcr-1 in CR-KP. Ethics approval Ethics approval for this study was granted by the Ethics Committee at the National Hospital of Pediatrics (reference no. VNCH-RICH-16-014). Funding This work was supported financially by Linköping University, the Karolinska Institute, the Training and Research Academic Collaboration (TRAC) – Sweden-Vietnam, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), ReAct and the Swedish Research Council. Transparency declarations None to declare. Supplementary data Figure S1 is available as Supplementary data at JAC Online. References 1 Lee CR, Lee JH, Park KS et al.   Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol  2016; 7: 895. Google Scholar PubMed  2 Liu YY, Wang Y, Walsh TR et al.   Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis  2016; 16: 161– 8. Google Scholar CrossRef Search ADS PubMed  3 Rolain JM, Kempf M, Leangapichart T et al.   Plasmid-mediated mcr-1 gene in colistin-resistant clinical isolates of Klebsiella pneumoniae in France and Laos. Antimicrob Agents Chemother  2016; 60: 6994– 5. Google Scholar CrossRef Search ADS PubMed  4 Tian GB, Doi Y, Shen J et al.   MCR-1-producing Klebsiella pneumoniae outbreak in China. Lancet Infect Dis  2017; 17: 577. Google Scholar CrossRef Search ADS PubMed  5 Le NK, Hf W, Vu PD et al.   High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: a multi-centre point prevalence survey. Medicine (Baltimore)  2016; 95: e4099. Google Scholar CrossRef Search ADS PubMed  6 Poirel L, Bonnin RA, Nordmann P. Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. Antimicrob Agents Chemother  2012; 56: 559– 62. Google Scholar CrossRef Search ADS PubMed  7 Zhi C, Lv L, Yu LF et al.   Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis  2016; 16: 292– 3. Google Scholar CrossRef Search ADS PubMed  8 Zhao F, Feng Y, Lü X et al.   IncP plasmid carrying colistin resistance gene mcr-1 in Klebsiella pneumoniae from hospital sewage. Antimicrob Agents Chemother  2017; 61: e02229-16. Google Scholar PubMed  9 Snesrud E, He S, Chandler M et al.   A model for transposition of the colistin resistance gene mcr-1 by ISApl1. Antimicrob Agents Chemother  2016; 60: 6973– 6. Google Scholar CrossRef Search ADS PubMed  10 Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence  2013; 4: 107– 18. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Journal

Journal of Antimicrobial ChemotherapyOxford University Press

Published: Apr 1, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off