A Patient With Multiple Carbapenemase Producers Including an Unusual Citrobacter sedlakii Hosting an IncC blaNDM-1- and armA-carrying Plasmid

Main Article Content

Aline Moser
Peter Keller
Edgar I. Campos-Madueno
Laurent Poirel
Patrice Nordmann
Andrea Endimiani

Abstract

Background. Patients colonized with multiple species of carbapenemase-producing Enterobacterales (CPE) are increasingly observed. This phenomenon can be due to the high local prevalence of these pathogens, the presence of important host risk factors, and the great genetic promiscuity of some carbapenemase genes.


Methods. We analyzed 4 CPE (Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Citrobacter sedlakii), 1 extended-spectrum cephalosporin-resistant K. pneumoniae (ESC-R-Kp), and 1 carbapenemase-producing Acinetobacter baumannii simultaneously isolated from a patient transferred from Macedonia. Susceptibility tests were performed using a microdilution MIC system. The complete genome sequences were obtained by using both short-read and long-read whole-genome sequencing technologies.


Results. All CPE presented high-level resistance to all aminoglycosides due to the expression of the armA 16S rRNA methylase. In C. sedlakii and E. coli (ST69), both the carbapenemase blaNDM-1 and armA genes were located on an identical IncC plasmid of type 1a. The K. pneumoniae (ST268) and P. stuartii carried chromosomal blaNDM-1 and blaOXA-48, respectively, while the ESC-R-Kp (ST395) harbored a plasmid-located blaCTX-M-15. In the latter 3 isolates, armA-harboring IncC plasmids similar to plasmids found in C. sedlakii and E. coli were also detected. The A. baumannii strain possessed the blaOXA-40 carbapenemase gene.


Conclusions. The characterization of the genetic organization of IncC-type plasmids harbored by 3 different species from the same patient offered insights into the evolution of these broad- host-range plasmids. Moreover, we characterized here the first complete genome sequence of a carbapenemase-producing C. sedlakii strain, providing a reference for future studies on this rarely reported species.

Article Details

Section
Articles
Author Biography

Andrea Endimiani, Institute for Infectious Diseases (IFIK), University of Bern, Bern, Switzerland

Institute for Infectious Diseases

Principal Investigator and Medical Microbiologist

References

Nordmann P, Poirel L. Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Clin Infect Dis. 2019;69(Suppl 7):S521-S8. doi: 10.1093/cid/ciz824. PubMed PMID: 31724045; PMCID: PMC6853758.

Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, Westblade LF. Carbapenemase-Producing Organisms: A Global Scourge. Clin Infect Dis. 2018;66(8):1290-7. doi: 10.1093/cid/cix893. PubMed PMID: 29165604; PMCID: PMC5884739.

Bush K. Past and Present Perspectives on beta-Lactamases. Antimicrob Agents Chemother. 2018;62(10). doi: 10.1128/AAC.01076-18. PubMed PMID: 30061284; PMCID: PMC6153792.

Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria. Biomed Res Int. 2014;2014:249856. doi: 10.1155/2014/249856. PubMed PMID: 24790993; PMCID: PMC3984790.

Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. NDM Metallo-beta-Lactamases and Their Bacterial Producers in Health Care Settings. Clin Microbiol Rev. 2019;32(2). doi: 10.1128/CMR.00115-18. PubMed PMID: 30700432; PMCID: PMC6431124.

Wachino JI, Doi Y, Arakawa Y. Aminoglycoside Resistance: Updates with a Focus on Acquired 16S Ribosomal RNA Methyltransferases. Infect Dis Clin North Am. 2020;34(4):887-902. doi: 10.1016/j.idc.2020.06.002. PubMed PMID: 33011054.

Tijet N, Muller MP, Matukas LM, Khan A, Patel SN, Melano RG. Lateral dissemination and inter-patient transmission of blaKPC-3: role of a conjugative plasmid in spreading carbapenem resistance. J Antimicrob Chemother. 2016;71(2):344-7. doi: 10.1093/jac/dkv356. PubMed PMID: 26518052.

Gona F, Barbera F, Pasquariello AC, Grossi P, Gridelli B, Mezzatesta ML, Caio C, Stefani S, Conaldi PG. In vivo multiclonal transfer of bla(KPC-3) from Klebsiella pneumoniae to Escherichia coli in surgery patients. Clin Microbiol Infect. 2014;20(10):O633-5. doi: 10.1111/1469-0691.12577. PubMed PMID: 24476498.

Aires-de-Sousa M, Ortiz de la Rosa JM, Goncalves ML, Costa A, Nordmann P, Poirel L. Occurrence of NDM-1-producing Morganella morganii and Proteus mirabilis in a single patient in Portugal: probable in vivo transfer by conjugation. J Antimicrob Chemother. 2020;75(4):903-6. doi: 10.1093/jac/dkz542. PubMed PMID: 31971235.

Arana DM, Saez D, Garcia-Hierro P, Bautista V, Fernandez-Romero S, Angel de la Cal M, Alos JI, Oteo J. Concurrent interspecies and clonal dissemination of OXA-48 carbapenemase. Clin Microbiol Infect. 2015;21(2):148 e1-4. doi: 10.1016/j.cmi.2014.07.008. PubMed PMID: 25596781.

Hammerum AM, Hansen F, Nielsen HL, Jakobsen L, Stegger M, Andersen PS, Jensen P, Nielsen TK, Hansen LH, Hasman H, Fuglsang-Damgaard D. Use of WGS data for investigation of a long-term NDM-1-producing Citrobacter freundii outbreak and secondary in vivo spread of blaNDM-1 to Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca. J Antimicrob Chemother. 2016;71(11):3117-24. doi: 10.1093/jac/dkw289. PubMed PMID: 27494919.

Zhu B, Ying C, Xu H, Ying J. Coexistence of NDM-1-producing Escherichia coli and Citrobacter freundii in the same patient. J Glob Antimicrob Resist. 2018;15:79-81. doi: 10.1016/j.jgar.2018.04.013. PubMed PMID: 29727717.

Bosch T, Lutgens SPM, Hermans MHA, Wever PC, Schneeberger PM, Renders NHM, Leenders A, Kluytmans J, Schoffelen A, Notermans D, Witteveen S, Bathoorn E, Schouls LM. Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers. J Clin Microbiol. 2017;55(8):2380-90. doi: 10.1128/JCM.00535-17. PubMed PMID: 28515215; PMCID: PMC5527415.

Ambrose SJ, Harmer CJ, Hall RM. Evolution and typing of IncC plasmids contributing to antibiotic resistance in Gram-negative bacteria. Plasmid. 2018;99:40-55. doi: 10.1016/j.plasmid.2018.08.001. PubMed PMID: 30081066.

Endimiani A, Ramette A, Rhoads DD, Jacobs MR. The Evolving Role of the Clinical Microbiology Laboratory in Identifying Resistance in Gram-Negative Bacteria: An Update. Infect Dis Clin North Am. 2020;34(4):659-76. doi: 10.1016/j.idc.2020.08.001. PubMed PMID: 33011047.

Bonnin RA, Nordmann P, Poirel L. Screening and deciphering antibiotic resistance in Acinetobacter baumannii: a state of the art. Expert Rev Anti Infect Ther. 2013;11(6):571-83. doi: 10.1586/eri.13.38. PubMed PMID: 23750729.

Campos-Madueno EI, Bernasconi OJ, Moser AI, Keller PM, Luzzaro F, Maffioli C, Bodmer T, Kronenberg A, Endimiani A. Rapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland Due to Spread of Common Plasmids and International Clones. Antimicrob Agents Chemother. 2020;64(10). doi: 10.1128/AAC.01057-20. PubMed PMID: 32718957; PMCID: PMC7508577.

Campos-Madueno EI, Gmuer C, Risch M, Bodmer T, Endimiani A. Characterisation of a new blaVIM-1-carrying IncN2 plasmid from an Enterobacter hormaechei subsp. steigerwaltii. J Glob Antimicrob Resist. 2021;24:325-7. doi: 10.1016/j.jgar.2021.01.017. PubMed PMID: 33571706.

Dadashi M, Yaslianifard S, Hajikhani B, Kabir K, Owlia P, Goudarzi M, Hakemivala M, Darban-Sarokhalil D. Frequency distribution, genotypes and prevalent sequence types of New Delhi metallo-beta-lactamase-producing Escherichia coli among clinical isolates around the world: A review. J Glob Antimicrob Resist. 2019;19:284-93. doi: 10.1016/j.jgar.2019.06.008. PubMed PMID: 31212107.

Weber RE, Pietsch M, Fruhauf A, Pfeifer Y, Martin M, Luft D, Gatermann S, Pfennigwerth N, Kaase M, Werner G, Fuchs S. IS26-Mediated Transfer of bla NDM-1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital. Front Microbiol. 2019;10:2817. doi: 10.3389/fmicb.2019.02817. PubMed PMID: 31921015; PMCID: PMC6929489.

Jovcic B, Lepsanovic Z, Begovic J, Rakonjac B, Perovanovic J, Topisirovic L, Kojic M. The clinical isolate Pseudomonas aeruginosa MMA83 carries two copies of the blaNDM-1 gene in a novel genetic context. Antimicrob Agents Chemother. 2013;57(7):3405-7. doi: 10.1128/AAC.02312-12. PubMed PMID: 23612199; PMCID: PMC3697382.

Poirel L, Bonnin RA, Boulanger A, Schrenzel J, Kaase M, Nordmann P. Tn125-related acquisition of blaNDM-like genes in Acinetobacter baumannii. Antimicrob Agents Chemother. 2012;56(2):1087-9. doi: 10.1128/AAC.05620-11. PubMed PMID: 22143526; PMCID: PMC3264265.

Bercot B, Poirel L, Nordmann P. Plasmid-mediated 16S rRNA methylases among extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates. Antimicrob Agents Chemother. 2008;52(12):4526-7. doi: 10.1128/AAC.00882-08. PubMed PMID: 18838598; PMCID: PMC2592896.

Bonnin RA, Nordmann P, Carattoli A, Poirel L. Comparative genomics of IncL/M-type plasmids: evolution by acquisition of resistance genes and insertion sequences. Antimicrob Agents Chemother. 2013;57(1):674-6. doi: 10.1128/AAC.01086-12. PubMed PMID: 23114767; PMCID: PMC3535931.

Di Pilato V, Errico G, Monaco M, Giani T, Del Grosso M, Antonelli A, David S, Lindh E, Camilli R, Aanensen DM, Rossolini GM, Pantosti A, pneumoniae A-ILSGoc-pK. The changing epidemiology of carbapenemase-producing Klebsiella pneumoniae in Italy: toward polyclonal evolution with emergence of high-risk lineages. J Antimicrob Chemother. 2021;76(2):355-61. doi: 10.1093/jac/dkaa431. PubMed PMID: 33188415.

Pitout JDD, Peirano G, Kock MM, Strydom KA, Matsumura Y. The Global Ascendency of OXA-48-Type Carbapenemases. Clin Microbiol Rev. 2019;33(1). doi: 10.1128/CMR.00102-19. PubMed PMID: 31722889; PMCID: PMC6860007.

Qamar MU, Walsh TR, Toleman MA, Tyrrell JM, Saleem S, Aboklaish A, Jahan S. Dissemination of genetically diverse NDM-1, -5, -7 producing-Gram-negative pathogens isolated from pediatric patients in Pakistan. Future Microbiol. 2019;14:691-704. doi: 10.2217/fmb-2019-0012. PubMed PMID: 31148474.

Rakhi NN, Alam A, Sultana M, Rahaman MM, Hossain MA. Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh. J Infect Chemother. 2019;25(6):444-51. doi: 10.1016/j.jiac.2019.01.010. PubMed PMID: 30824303.

Toleman MA, Bennett PM, Walsh TR. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev. 2006;70(2):296-316. doi: 10.1128/MMBR.00048-05. PubMed PMID: 16760305; PMCID: PMC1489542.

Samuelsen O, Overballe-Petersen S, Bjornholt JV, Brisse S, Doumith M, Woodford N, Hopkins KL, Aasnaes B, Haldorsen B, Sundsfjord A, Norwegian Study Group on CPE. Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014. PLoS One. 2017;12(11):e0187832. doi: 10.1371/journal.pone.0187832. PubMed PMID: 29141051; PMCID: PMC5687771.

Savov E, Politi L, Spanakis N, Trifonova A, Kioseva E, Tsakris A. NDM-1 Hazard in the Balkan States: Evidence of the First Outbreak of NDM-1-Producing Klebsiella pneumoniae in Bulgaria. Microb Drug Resist. 2018;24(3):253-9. doi: 10.1089/mdr.2017.0230. PubMed PMID: 28876169.

Brkic S, Bozic D, Stojanovic N, Vitorovic T, Topalov D, Jovanovic M, Stepanovic M, Cirkovic I. Antimicrobial Susceptibility and Molecular Characterization of Carbapenemase-Producing Enterobacter spp. Community Isolates in Belgrade, Serbia. Microb Drug Resist. 2020;26(4):378-84. doi: 10.1089/mdr.2019.0224. PubMed PMID: 31651210.

Politi L, Gartzonika K, Spanakis N, Zarkotou O, Poulou A, Skoura L, Vrioni G, Tsakris A. Emergence of NDM-1-producing Klebsiella pneumoniae in Greece: evidence of a widespread clonal outbreak. J Antimicrob Chemother. 2019;74(8):2197-202. doi: 10.1093/jac/dkz176. PubMed PMID: 31065697.

Seiffert SN, Perreten V, Johannes S, Droz S, Bodmer T, Endimiani A. OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky isolate of sequence type 198 in a patient transferred from Libya to Switzerland. Antimicrob Agents Chemother. 2014;58(4):2446-9. doi: 10.1128/AAC.02417-13. PubMed PMID: 24468781; PMCID: PMC4023741.

Seiffert SN, Marschall J, Perreten V, Carattoli A, Furrer H, Endimiani A. Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland. Int J Antimicrob Agents. 2014;44(3):260-2. doi: 10.1016/j.ijantimicag.2014.05.008. PubMed PMID: 25123809.

Clement M, Keller PM, Bernasconi OJ, Stirnimann G, Frey PM, Bloemberg GV, Sendi P, Endimiani A. First Clinical Case of In Vivo Acquisition of DHA-1 Plasmid-Mediated AmpC in a Salmonella enterica subsp. enterica Isolate. Antimicrob Agents Chemother. 2019;63(10). doi: 10.1128/AAC.00992-19. PubMed PMID: 31358582; PMCID: PMC6761535.