Research Article
25 April 2019

Molecular Characterization of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Hospitals in Myanmar

ABSTRACT

The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa has become a serious worldwide medical problem. This study was designed to clarify the genetic and epidemiological properties of MDR P. aeruginosa strains isolated from hospitals in Myanmar. Forty-five MDR P. aeruginosa isolates obtained from different patients in seven hospitals in Myanmar were screened using the broth microdilution method. The whole genomes of the MDR isolates were sequenced using a MiSeq platform (Illumina). Phylogenetic trees were constructed from single nucleotide polymorphism concatemers. Multilocus sequence types were deduced, and drug resistance genes were identified. Of the 45 isolates, 38 harbored genes encoding carbapenemases, including DIM-1, IMP-1, NDM-1, VIM-2, and VIM-5, and 9 isolates had genes encoding 16S rRNA methylases, including RmtB, RmtD3, RmtE, and RmtF2. Most MDR P. aeruginosa strains isolated in Myanmar belonged to sequence type 1047 (ST1047). This is the first molecular epidemiological analysis of MDR P. aeruginosa clinical isolates in Myanmar. These findings strongly suggest that P. aeruginosa ST1047 strains harboring carbapenemases, including DIM-, IMP-, NDM-, and VIM-type metallo-β-lactamases, have been spreading throughout medical settings in Myanmar.

INTRODUCTION

The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa has become a serious worldwide medical problem (1, 2). Most MDR P. aeruginosa isolates encode carbapenem and aminoglycoside resistance factors, including metallo-β-lactamases (MBLs), aminoglycoside-modifying enzymes, and 16S rRNA methylases (1, 2). In particular, MBLs and 16S rRNA methylases are associated with high resistance to carbapenems and aminoglycosides, respectively.
MBLs confer resistance to all β-lactams, except the monobactams, and are characterized by their efficient hydrolysis of carbapenems (3). P. aeruginosa isolates producing IMP- or VIM-type MBLs have been detected in various Asian countries (4). For example, isolates producing IMP-type MBLs have been observed in China, Japan, South Korea, Malaysia, Singapore, Thailand, and Vietnam, and isolates producing VIM-type MBLs have been identified in China, India, Indonesia, South Korea, Malaysia, Saudi Arabia, and Taiwan (5, 6). In addition, a P. aeruginosa isolate producing an NDM-type MBL has been reported in India (7). In non-Asian countries, IMP-type MBL-producing P. aeruginosa clinical isolates were detected in Australia, Belgium, Brazil, Canada, the Czech Republic, Denmark, France, Germany, Portugal, and Slovakia, whereas VIM-type MBL producers were detected in Argentina, Austria, Belgium, Bulgaria, Chile, Columbia, Croatia, Egypt, France, Germany, Greece, Hungary, Italy, Kenya, Mexico, Poland, Portugal, Spain, Sweden, Tunisia, the United Kingdom, the United States, and Venezuela (8).
Acquired 16S rRNA methylase genes responsible for extremely high levels of resistance to various aminoglycosides are widely distributed among Gram-negative bacteria, including Enterobacteriaceae and glucose-nonfermentative bacteria (9). To date, 10 kinds of 16S rRNA methylases, including ArmA, RmtA, RmtB, RmtC, RmtD, RmtE, RmtF, RmtG, RmtH, and NpmA, have been found in clinical isolates (1013).
This is the first molecular epidemiological analysis of MDR P. aeruginosa clinical isolates in Myanmar. Our present study, therefore, would be useful to understand the dynamics of MDR P. aeruginosa strains in Asian countries.

RESULTS

Drug susceptibility and drug resistance factors.

All 45 MDR isolates were sensitive to colistin (Table 1), and all 45 isolates were resistant to amikacin and ciprofloxacin. Thirty-five isolates (77.8%) were resistant to aztreonam, 39 isolates (86.7%) were resistant to cefepime, 44 isolates (97.8%) were resistant to ceftazidime, 40 isolates (88.9%) were resistant to imipenem, and 44 isolates (97.8%) were resistant to meropenem.
TABLE 1
TABLE 1 MIC90 and MIC50 values and percent antimicrobial resistance of MDR P. aeruginosa clinical isolatesa
Antimicrobial agentBreakpoint for
resistance (μg/ml)b
% resistanceMIC data (μg/ml)
RangeMIC50MIC90
Amikacin≥6410064 to >1,024256>1,024
Aztreonam≥3277.88 to >1,02432>1,024
Cefepime≥3286.78 to >1,024512>1,024
Ceftazidime≥3297.84 to >1,024>1,024>1,024
Ciprofloxacin≥41004 to >1,02464128
Colistin≥800.063 to 10.50.5
Imipenem≥888.91 to 512128512
Meropenem≥897.82 to 1,024128512
a
n = 45.
b
Breakpoints for antimicrobial resistance were determined according to the guidelines of the Clinical and Laboratory Standards Institute.
Of the 45 MDR P. aeruginosa isolates, 38 (84.4%) encoded metallo-β-lactamase genes, including DIM-1, IMP-1, NDM-1, VIM-1, VIM-2, and VIM-5 (Table 2). Of these, 12 harbored genes encoding both DIM-1 and NDM-1, and one harbored genes encoding both IMP-1 and NDM-1. None of these isolates harbored other carbapenemase-encoding genes.
TABLE 2
TABLE 2 Characterization of multidrug-resistant P. aeruginosa isolatesa
MLSTNo. of isolates belonging to same STHospital(s)No. of strains harboring the gene/total no. of strains for:QRDR (no. of strains with the amino acid substitution/total no. of strains) forb:
Carbapenemase-encoding gene(s)Aminoglycoside resistance gene(s)cGyrAParC
ST2335A, B, GblaVIM-2aacA7, aacA5, aadA2 (2/5)S83IS80L
ST2354A, CblaIMP-1 (2/4), blaNDM-1 (1/4)aacA1 (1/4), aacA4 (2/4), aacC5 (1/4), aadA1 (3/4), aadA6, aadBS83IS80L (2/4)
ST2734A, B, DblaNDM-1 (3/4)rmtB (1/4), rmtE, aacA4 (2/4), aadA1, aadBS83I, D87HS80L
ST3141AblaNDM-1aacA4S83IS80L
ST3161C rmtD3, aacA4S83I 
ST3573D, FblaVIM-2 (1/3), blaVIM-5 (2/3)aacA4 (1/3), aacA7 (1/3), aacC5 (1/3), aadA1 (1/3)S83I (2/3), S83T (1/3)S80L (2/3)
ST4461AblaVIM-2aacA7, aacC5S83IS80L
ST9832C rmtF2, aacA4S83I, D87NS80L
ST104723A, B, GblaDIM-1 (12/23), blaNDM-1 (15/23), blaVIM-2 (8/23)rmtB4 (2/23), aacA4 (6/23), aadA1 (6/23)S83I (22/23), S83L (1/23), D87N (1/23)S80L
ST11211A aadA1S83IS80L
a
n = 45.
b
QRDR, quinolone resistance-determining region.
c
Aminoglycoside resistance genes, including those encoding aminoglycoside-acetyltransferase and aminoglycoside-adenylyltransferase.
Nine (20.0%) of the 45 isolates harbored genes encoding 16S rRNA methylase, including RmtB4, RmtD3, RmtE, and RmtF2 (Table 2). One isolate harbored genes encoding both RmtB and RmtE. In addition, the isolates harbored genes encoding various aminoglycoside-modifying enzymes, including AacA1, AacA4, AacA7, AacC5, AadA1, AadA2, AadA6, and AadB.
All 45 isolates were found to have point mutations in the quinolone resistance-determining regions of gyrA and/or parC, containing one to three amino acid substitutions. Of the 45 isolates, 35 (77.8%) had the amino acid substitutions Ser83Ile in GyrA and Ser80Leu in ParC, four (8.9%) had the substitutions Ser83Ile and Asp87His in GyrA and Ser80Leu in ParC, two (4.4%) had amino acid substitutions Ser83Ile and Asp87Asn in GyrA and Ser80Leu in ParC, two (4.4%) had the substitution Ser83Ile in GyrA, one (2.2%) had the substitutions Ser83Leu and Asp87Glu in GyrA and Ser80Leu in ParC, and one (2.2%) had the substitution Ser83Thr in GyrA (Table 2).

MLST and phylogenetic analysis.

Of the 45 MDR P. aeruginosa isolates in Myanmar, 23 (51.1%) belonged to sequence type 1047 (ST1047) (allelic profile 18, 8, 5, 5, 1, 6, 4). In addition, five (11.1%) isolates belonged to ST233, four (8.9%) isolates belonged to ST235, four (8.9%) isolates belonged to ST273, three (6.7%) isolates belonged to ST357, two (4.4%) isolates belonged to ST983, and one (2.2%) isolate each belonged to ST314, ST316, ST446, and ST1121 (Table 2). The phylogenetic tree revealed four clades designated clades I, II, III, and IV. Clade I consisted of the isolates belonging to ST1047, clade II of the isolates belonging to ST316, ST357, ST446, and ST1121, clade III of the isolates belonging to ST235, and clade IV of the isolates belonging to ST233, ST273, ST314, and ST549 (reference strain,P. aeruginosa PAO1) and ST983. The 23 strains of P. aeruginosa ST1047 (clade I) were isolated from hospitals A, B, and G and found to have spread in a clonal manner (Fig. 1).
FIG 1
FIG 1 Molecular phylogenetic tree of the 45 MDR P. aeruginosa strains isolated in medical settings in Myanmar. A maximum likelihood phylogenetic tree was constructed from the 45 MDR isolates.

Genomic environments surrounding carbapenemase-encoding genes.

Sequences derived from each contig after assembling the raw read data showed that seven types of genetic structures surrounded the carbapenemase-encoding genes, including blaDIM-1, blaIMP-1, blaNDM-1, blaVIM-2, and blaVIM-5 (Fig. 2). The environment surrounding blaDIM-1 was intI1-blaDIM-1-orf1-trpR-tnpA (type A in Fig. 2). The structure was a unique gene cassette array, although the structure, intI1-blaIMP-1-aacA4, was frequently identified in IMP-type MBL-producing P. aeruginosa strains in Asian countries, including Japan and South Korea (1). The genomic environment surrounding blaNDM-1 was IS91-blaNDM-1-IS91-mrsB-mrsA-orf2-corA-orf3-tnpA (type C in Fig. 2). The structure IS91-blaNDM-1-IS91 was identical to that in a chromosome of P. aeruginosa N15-01092, which was identified in 2015 in Canada (GenBank accession no. CP012901). The genomic environment surrounding blaIMP-1, intI1-blaIMP-1-aacA4-IS1595, was unique (type B in Fig. 2). The genomic environment surrounding blaVIM-2 consisted of three types of genetic structures (types D, E, and F in Fig. 2). The structure D, intI1-aacA7-blaVIM-2-dfrB-aacC5-tniR-tniQ-tniB-tniA, was identical to that of the chromosome of P. aeruginosa K34-7 identified in 2006 in Norway (GenBank accession no. CP029707) (14) and PA83 in 2013 in Germany (GenBank accession no. CP017293). The structure E, intI1-orf4-blaVIM-2-tniC-tniQ-tniB-tniA, was identical to that in the plasmid of Pseudomonas putida PPV2-2 (GenBank accession no. GQ227991) identified in 2005 in Spain (15). The structure F, intI1-qnrVC1-aacA4-blaVIM-2-tniC-tniQ-tniB-tniA, was a unique gene cassette array, although part of this structure, aacA4-blaVIM-2-tniC-tniQ-tniB-tniA, was identical to that in the transposon Tn5090 of P. aeruginosa R22 in China (GenBank accession no. AM993098). The genetic environment surrounding blaVIM-5 was intI1-blaVIM-5-aadB-dfrA1-orf5-qacEΔ1-sulI. The structure, intI1-blaVIM-5-aadB, was identical to that in the plasmid of VIM-1-producing P. aeruginosa strain PAMBL-1 (GenBank accession no. GQ422829) in 2007 in Spain (16).
FIG 2
FIG 2 Structures of the genomic environments surrounding carbapenemase-encoding genes, including blaDIM-1 (A), blaIMP-1 (B), blaNDM-1 (C), blaVIM-2 (D to F), and blaVIM-5 (G). orf1, haloacid dehalogenase type II-encoding gene; orf2, glutathione S-transferase-encoding gene; orf3, hypothetical protein-encoding gene; orf4, putative AAC(6′)-encoding gene; orf5, hypothetical protein-encoding gene.
Pulsed-field gel electrophoresis (PFGE) and Southern hybridization analyses revealed that 8 of 11 isolates harbored plasmids ranging in the sizes from 48 to 145 kbp (see Table S1 in the supplemental material). None of these isolates contained a plasmid harboring blaDIM-1, blaIMP-1, blaNDM-1, blaVIM-2, and/or blaVIM-5 (data not shown), indicating that these genes were located on the chromosomes.

DISCUSSION

To our knowledge, this is the first molecular epidemiological analysis of MDR P. aeruginosa clinical isolates in Myanmar. Of the MDR P. aeruginosa isolates tested in Myanmar, 84.4% possessed genes encoding carbapenemases, including DIM-1, IMP-1, NDM-1, VIM-2, and VIM-5, and 20% of the isolates possessed genes encoding 16S rRNA methylases, including RmtB, RmtD3, RmtE, and RmtF2. These genes likely contributed to the high resistance of P. aeruginosa isolates in Myanmar to carbapenems and aminoglycosides.
Another key finding of this study was that the majority (51.1%) of MDR P. aeruginosa clinical isolates in Myanmar belonged to ST1047. To date, only one P. aeruginosa isolate belonging to ST1047 had been registered in the MLST website. This isolate, identified in Norway in 2010, was found to produce VIM-type MBLs. Recently, VIM-2-producing P. aeruginosa ST1047 isolates were obtained from dogs in South Korea with pyoderma and otitis (17). P. aeruginosa high-risk clones, including ST233, ST235, and ST357, were also identified in Myanmar but from only 26.7% of the 45 isolates. Further studies are needed to determine whether MDR P. aeruginosa isolates belonging to ST1047 are emerging and spreading in countries neighboring Myanmar, including Bangladesh, China, Laos, India, and Thailand. These results indicate that MDR P. aeruginosa strains may evolve in unique environments in Myanmar, such as the climate and the antibiotic usage, because ST1047 strains, which had completely different allelic profiles from those of ST235 strains, were spreading in medical settings in Myanmar.
P. aeruginosa ST1047 strains may have the ability to integrate various drug resistance factors, including carbapenemases, 16S rRNA methylases, and aminoglycoside-modifying enzymes, suggesting that P. aeruginosa ST1047 may become a high-risk clone in Southeast Asia. Most P. aeruginosa isolates obtained to date from medical settings in Southeast Asian countries belong to the high-risk clone ST235, but some isolates belonging to the high-risk clones ST111 and/or ST175 have been obtained from medical settings in East and South Asian countries, including China, India, Japan, and South Korea (1).
Our study strongly suggests that P. aeruginosa ST1047 has been spreading throughout medical settings in Myanmar. It is necessary to survey MDR P. aeruginosa isolates in medical settings in Myanmar.

MATERIALS AND METHODS

Bacterial isolates.

Forty-five isolates of MDR P. aeruginosa, defined as strains showing resistance to carbapenem (MIC, ≥8 μg/ml), amikacin (MIC, ≥64 μg/ml), and fluoroquinolones (MIC, ≥4 μg/ml) (18), were obtained between December 2015 and May 2017 from patients treated at seven hospitals in Myanmar (26 isolates from hospital A, eight from hospital B, four from hospital C, three from hospital D, two from hospital E, and one each from hospitals F and G). Bacteria were identified using the Vitek 2 system (bioMérieux, Marcy l’Etoile, France), with identities confirmed by sequencing of 16S rRNA (19). Of the 45 isolates, 18 isolates were from wounds, 14 isolates were from urine, six isolates were from sputum, three isolates were from pus, and one isolate each was from blood, bone pus, an endotracheal tube, and a nasopharyngeal swab. MICs were determined using the broth microdilution method (18).

Whole-genome sequencing.

Genomic DNAs of the 45 isolates were extracted using DNeasy blood and tissue kits (Qiagen, Tokyo, Japan) and sequenced using the MiSeq platform (Illumina, San Diego, CA) with the Nextera XT DNA library prep kit and MiSeq reagent kit version 3 (600 cycle; Illumina). More than 31-fold coverage was achieved for each isolate. Raw reads of each isolate were assembled using CLC Genomics Workbench version 8.0.2, and drug resistance genes were identified using ResFinder 3.0 (https://cge.cbs.dtu.dk//services/ResFinder/). The criteria for ResFinder 3.0 were defined as select threshold for identification (ID) of 90% and select minimum length of 80%. Fluoroquinolone resistance has been associated with mutations in the quinolone resistance-determining region, which includes the gyrA and parC genes that encode DNA gyrase and topoisomerase IV, respectively (20). Multilocus sequence typing (MLST) was deduced, as described by the protocols of the PubMLST (http://pubmlst.org/paeruginosa/) databases.

Phylogenetic analysis based on SNPs.

To identify single nucleotide polymorphisms (SNPs) among the 45 whole genomes, all reads of each isolate were aligned against the P. aeruginosa PAO1 sequence (GenBank accession no. AE004091) using CLC Genomics Workbench version 8.0.2 (CLC bio, Tokyo, Japan). SNP concatenated sequences were aligned by MAFFT (http://mafft.cbrc.jp/alignment/server/). Models and parameters used for the phylogenetic analyses were computed using j-Model Test-2.1.4. A maximum likelihood phylogenetic tree was constructed from SNP alignment with PhyML 3.0 (21).

Pulsed-field gel electrophoresis and Southern hybridization.

Plasmids from each ST strain (11 isolates), which harbored the blaDIM-1, blaIMP-1, blaNDM-1, blaVIM-2, and/or blaVIM-5 genes, were extracted (Table S1) and separated by pulsed-field gel electrophoresis (22). Southern hybridization was performed using probes of each of the above-mentioned genes. Signal detections were carried out using DIG High Prime DNA labeling and detection starter kit II (Roche Applied Science, Indianapolis, IN, USA).

Data availability.

The whole-genome sequences of all 45 isolates were deposited at GenBank as accession number DRA007442 (experiment accession numbers DRX143958 to DRX144002 and run numbers DRR153275 to DRR153319).

ACKNOWLEDGMENTS

This study was supported by grants from the Japan Society for the Promotion of Science (grant 18K07120) and the Research Program on Emerging and Re-emerging Infectious Diseases from the Japan Agency for Medical Research and Development (grant 18fk0108061). S.W. received the endowed chair from Asahi Group Holdings, Ltd.

Supplemental Material

File (aac.02397-18-s0001.xlsx)
ASM does not own the copyrights to Supplemental Material that may be linked to, or accessed through, an article. The authors have granted ASM a non-exclusive, world-wide license to publish the Supplemental Material files. Please contact the corresponding author directly for reuse.

REFERENCES

1.
Oliver A, Mulet X, López-Causapé C, Juan C. 2015. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist Updat 21-22:41–59.
2.
Treepong P, Kos VN, Guyeux C, Blanc DS, Bertrand X, Valot B, Hocquet D. 2018. Global emergence of the widespread Pseudomonas aeruginosa ST235 clone. Clin Microbiol Infect 24:258–266.
3.
Bush K. 2001. New β-lactamases in Gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy. Clin Infect Dis 32:1085–1089.
4.
Cornaglia G, Giamarellou H, Rossolini GM. 2011. Metallo-β-lactamases: a last frontier for β-lactams? Lancet Infect Dis 11:381–393.
5.
Tada T, Miyoshi-Akiyama T, Shimada K, Shimojima M, Kirikae T. 2013. IMP-43 and IMP-44 metallo-β-lactamases with increased carbapenemase activities in multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:4427–4432.
6.
Kim MJ, Bae IK, Jeong SH, Kim SH, Song JH, Choi JY, Yoon SS, Thamlikitkul V, Hsueh PR, Yasin RM, Lalitha MK, Lee K. 2013. Dissemination of metallo-β-lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries. J Antimicrob Chemother 68:2820–2824.
7.
Shanthi M, Sekar U, Kamalanathan A, Sekar B. 2014. Detection of New Delhi metallo-β-lactamase-1 (NDM-1) carbapenemase in Pseudomonas aeruginosa in a single centre in southern India. Indian J Med Res 140:546–550.
8.
Hong DJ, Bae IK, Jang IH, Jeong SH, Kang HK, Lee K. 2015. Epidemiology and characteristics of metallo-β-lactamase-producing Pseudomonas aeruginosa. Infect Chemother 47:81–97.
9.
Wachino J-i, Yamane K, Shibayama K, Kurokawa H, Shibata N, Suzuki S, Doi Y, Kimura K, Ike Y, Arakawa Y. 2006. Novel plasmid-mediated 16S rRNA methylase, RmtC, found in a proteus mirabilis isolate demonstrating extraordinary high-level resistance against various aminoglycosides. Antimicrob Agents Chemother 50:178–184.
10.
Wachino J, Arakawa Y. 2012. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update. Drug Resist Updat 15:133–148.
11.
Galimand M, Courvalin P, Lambert T. 2012. RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family. Antimicrob Agents Chemother 56:3960–3962.
12.
Bueno MF, Francisco GR, O’Hara JA, de Oliveira Garcia D, Doi Y. 2013. Co-production of 16S ribosomal RNA methyltransferase RmtD and RmtG with KPC-2 and CTX-M-group ESBLs in Klebsiella pneumoniae. Antimicrob Agents Chemother 57:2397–2400.
13.
O'Hara JA, McGann P, Snesrud EC, Clifford RJ, Waterman PE, Lesho EP, Doi Y. 2013. Novel 16S ribosomal RNA methyltransferase RmtH produced by Klebsiella pneumoniae associated with war-related trauma. Antimicrob Agents Chemother 57:2413–2416.
14.
Taiaroa G, Samuelsen O, Kristensen T, Okstad OAL, Heikal A. 2018. Complete genome sequence of Pseudomonas aeruginosa K34-7, a carbapenem-resistant isolate of the high-risk sequence type 233. Microbiol Resour Announc 7:e00886-18.
15.
Juan C, Zamorano L, Mena A, Alberti S, Perez JL, Oliver A. 2010. Metallo-β-lactamase-producing Pseudomonas putida as a reservoir of multidrug resistance elements that can be transferred to successful Pseudomonas aeruginosa clones. J Antimicrob Chemother 65:474–478.
16.
Tato M, Coque TM, Baquero F, Canton R. 2010. Dispersal of carbapenemase blaVIM-1 gene associated with different Tn402 variants, mercury transposons, and conjugative plasmids in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 54:320–327.
17.
Hyun JE, Chung TH, Hwang CY. 2018. Identification of VIM-2 metallo-β-lactamase-producing Pseudomonas aeruginosa isolated from dogs with pyoderma and otitis in Korea. Vet Dermatol 29:186–e68.
18.
Clinical and Laboratory Standards Institute. 2018. Performance standards for antimicrobial susceptibility testing; 28th informational supplement. CLSI M100-S28. Clinical and Laboratory Standards Institute, Wayne, PA.
19.
Suzuki MT, Taylor LT, DeLong EF. 2000. Quantitative analysis of small-subunit rRNA genes in mixed microbial populations via 5′-nuclease assays. Appl Environ Microbiol 66:4605–4614.
20.
Nakano M, Deguchi T, Kawamura T, Yasuda M, Kimura M, Okano Y, Kawada Y. 1997. Mutations in the gyrA and parC genes in fluoroquinolone-resistant clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 41:2289–2291.
21.
Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. 2010. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59:307–321.
22.
Tada T, Shrestha B, Miyoshi-Akiyama T, Shimada K, Ohara H, Kirikae T, Pokhrel BM. 2014. NDM-12, a novel New Delhi metallo-β-lactamase variant from a carbapenem-resistant Escherichia coli clinical isolate in Nepal. Antimicrob Agents Chemother 58:6302–6305.

Information & Contributors

Information

Published In

cover image Antimicrobial Agents and Chemotherapy
Antimicrobial Agents and Chemotherapy
Volume 63Number 5May 2019
eLocator: 10.1128/aac.02397-18

History

Received: 20 November 2018
Returned for modification: 21 December 2018
Accepted: 19 February 2019
Published online: 25 April 2019

Permissions

Request permissions for this article.

Keywords

  1. 16S rRNA methylases
  2. Pseudomonas aeruginosa
  3. aminoglycoside-modifying enzymes
  4. carbapenemase
  5. molecular epidemiology

Contributors

Authors

Tatsuya Tada
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
Tomomi Hishinuma
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
Shin Watanabe
Department of Microbiome Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
Hiroki Uchida
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
Mari Tohya
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
Kyoko Kuwahara-Arai
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
San Mya
National Health Laboratory, Yangon, Myanmar
Khin Nyein Zan
National Health Laboratory, Yangon, Myanmar
Teruo Kirikae
Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan
Htay Htay Tin
National Health Laboratory, Yangon, Myanmar

Notes

Address correspondence to Teruo Kirikae, [email protected].

Metrics & Citations

Metrics

Note:

  • For recently published articles, the TOTAL download count will appear as zero until a new month starts.
  • There is a 3- to 4-day delay in article usage, so article usage will not appear immediately after publication.
  • Citation counts come from the Crossref Cited by service.

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

View Options

Figures and Media

Figures

Media

Tables

Share

Share

Share the article link

Share with email

Email a colleague

Share on social media

American Society for Microbiology ("ASM") is committed to maintaining your confidence and trust with respect to the information we collect from you on websites owned and operated by ASM ("ASM Web Sites") and other sources. This Privacy Policy sets forth the information we collect about you, how we use this information and the choices you have about how we use such information.
FIND OUT MORE about the privacy policy