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Putative horizontal transfer of carbapenem resistance between Klebsiella pneumoniae and Kluyvera ascorbata during abdominal infection: A case report

Published online by Cambridge University Press:  15 February 2019

Otávio Hallal Ferreira Raro*
Affiliation:
Departamento de Ciências da saúde da Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
Daiana de Lima-Morales
Affiliation:
LABRESIS - Laboratório de Pesquisa em Resistência Bacteriana, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
Afonso Luis Barth
Affiliation:
LABRESIS - Laboratório de Pesquisa em Resistência Bacteriana, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
Tiago Galvão Paim
Affiliation:
Instituto de Biociências da Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, Rio Grande do Sul, Brazil, Brazil
Mariana Preussler Mott
Affiliation:
Departamento de Ciências da saúde da Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
Cezar Vinícius Würdig Riche
Affiliation:
Departamento de Ciências da saúde da Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
Uirá Fernandes Teixeira
Affiliation:
Serviço de Cirurgia do Aparelho Digestivo da UFCSPA/Santa Casa – UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
Fábio Luiz Waechter
Affiliation:
Serviço de Cirurgia do Aparelho Digestivo da UFCSPA/Santa Casa – UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
Cícero Armídio Gomes Dias
Affiliation:
Departamento de Ciências da saúde da Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, Rio Grande do Sul, Brazil
*
Author for correspondence: Otávio Hallal Ferreira Raro, Email: otaviohraro@gmail.com
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Abstract

Type
Letter to the Editor
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. 

To the Editor—The emergence of KPC-producing Enterobacter has led to the development of serious infections related to high levels of mortality and morbidity worldwide.Reference Ben-David, Kordevani and Keller1, Reference Patel, Huprikar, Factor, Jenkins and Calfee2 The rapid spread of KPCs is linked to multiple elements, such as plasmid-borne genes and the dissemination by international travelers; these bacteria are frequently multidrug resistant, causing untreatable infections.Reference Pitout, Nordmann and Poirel3, Reference Porreca, Sullivan and Gallagher4 Kluyvera spp is a genus of gram-negative rods of the Enterobacteriaceae family.Reference Farmer, Fanning and Huntley-Carter5 Although it is a commensal of the human gut microbiota,Reference Carter and Evans6 Kluyvera spp has the potential to cause septic shock, urinary tract infections, catheter-associated bloodstream infections, and abdominal infections.Reference Thele, Gumpert and Christensen7 Here, we report a case of a plasmid-mediated horizontal transfer from a Klebsiella pneumoniae isolate to a Kluyvera ascorbata isolate during abdominal infection. The patient approved the data submission.

A 43-year-old male patient was admitted to the Hepatobiliary and Pancreatic Surgical Division from a hospital in the South Region of Brazil in October 2016. He was asymptomatic but had an incidental type 1 biliary cyst that was discovered during ultrasonography. Magnetic resonance imaging (MRI) with cholangiopancreatography was performed for adequate evaluation and showed an abnormal pancreatobiliary junction, as well. In November 2016, the patient underwent a cholecystectomy and total resection of the cyst, with closure of distal part of the main bile duct inside the pancreas, accompanied by Roux-en-Y hepaticojejunostomy to provide proper biliary drainage. The pathology report showed no malignancy in surgical specimen. After 48 hours, the patient was evaluated with postoperative pancreatitis and signs of sepsis, therefore piperacillin/tazobactam treatment was started. The patient continued to present clinical deterioration and needed parenteral nutrition; he was consequently transferred to the intensive care unit (ICU). Blood cultures were negative and abdominal computerized tomography (CT) showed abdominal collections. CT-guided drainage of pancreatic fluid was performed and cultures were negative. Nevertheless, antimicrobial treatment with meropenem was started and continued for 14 days without resolution. A second CT-guided drainage procedure was performed at the end of December, and the bacteriological culture yielded a multisusceptible Enterococcus faecalis; a Kluyvera ascorbata resistant to ampicillin and second-generation cephalosporin but susceptible to carbapenem, and multidrug-resistant Klebsiella pneumoniae, including resistance to tigecycline and carbapenem. Antibiotics were adjusted to vancomycin, meropenem, and ertapenem plus polymyxin B with clinical improvement but without complete bacterial clearance. After 17 days, a third CT-guided drainage was performed, and the bacterial culture yielded 1 K. ascorbata isolate resistant to carbapenem. A fourth CT-guided drainage was performed after 15 days, and the culture yielded K. ascorbata susceptible to carbapenem and K. pneumoniae resistant to carbapenem. Antibiotic treatment was adjusted to polymyxin B, tigecycline, and sulfametoxazol-trimetoprim, and the patient was evaluated with signs of controlled infection. After 14 days, the antibiotic treatment was suspended, and a final CT showed no signs of abdominal collections. The patient was discharged and was followed as an outpatient.

In this case, 2 isolates were collected: 1 from the second CT, named K. pneumoniae KpOT1, and 1 from the third CT, named K. ascorbata KaOT2. Both were resistant to meropenem. They were forwarded to a molecular investigation of carbapenemase genes through conventional PCR, and both were bla KPC-2 positive. Conjugation experiments were performed using the azide-resistant E. coli J53 as the receptor strain. One transconjugant was obtained from each isolate; both presented an increase in the minimum inhibitory concentration (MIC)8 for meropenem, from <0.0625 µg/mL to 2 µg/mL (KpOT1 transconjugant) and 1 µg/mL, (KaOT2 transconjugant), confirming the transferability of the plasmids. The susceptibility profiles of KpOT1, KaOT2, and the transconjugants are shown in Table 1.

Table 1. Antimicrobial Resistance Profile of the Klebsiella pneumoniae and Kluyvera ascorbata Pathogenic Isolates and the Transconjugants TKp and TKa

Note. AMP, ampicillin; ASB, ampicillin-sulbactam; CFZ, cefazolin; CAZ, ceftazidime; FEP, cefepime; SXT, trimethoprim/sulfamethoxazole; AK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; MER, meropenem; IMP, imipenem; ERT, ertapenem; PTZ, piperacillin/tazobactam; MIC, minimum inhibitory concentration; aph(3’)-la, aminoglycoside resistance; aac(6’)Ib-cr, fluoroquinolone and aminoglycoside resistance; bla KPC-2, β-lactam resistance; bla SHV-11, β-lactam resistance; bla CTX-M-15, β-lactam resistance; bla OXA-1, β-lactam resistance; oqxA, quinolone resistance; oqxB, quinolone resistance; fosA, fosfomycin resistance; mph(A), macrolide resistance; catB4, phenicol resistance; sul1, sulphonamide resistance; tet(A), tetracycline resistance; dfrA30, trimethoprim resistance; bla CTX-M-56, β-lactam resistance.

To better analyze the bla KPC-2 carrying plasmids, the whole genomes from both strains were sequenced using the Illumina MiSeq platform (San Diego, CA). Detailed analyses indicated that the bla KPC-2 was located on an IncN plasmid. The carbapenemase resistance gene was flanked by the insertion sequences ISKpn7 and ISKpn6, located on a Tn4401 transposon, isoform b.Reference Naas, Cuzon, Truong and Nordmann9 The scaffold bearing the bla KPC-2 was 50,417 bp long, and no other resistance gene was found in this scaffold. The IncN plasmid was also found in the K. ascorbata genome, containing the same bla KPC-2 resistance gene and the same genome environment, indicating that a plasmid transference occurred between KpOT1 and KaOT2 when the patient was in the hospital unit. Further in silico analyses indicated that K. pneumoniae KpOT1 belonged to the sequence type ST437, one of the most prevalent sequence types among the KPC-producing K. pneumoniae and related to the clonal complex 258, which is distributed worldwide.Reference Fehlberg, Carvalho, Campana, Gontijo-Filho and Gales10, Reference Seki, Pereira and Maria da Penh11 Other resistance genes were identified in both isolates (Table 1). This whole-genome shotgun sequencing project has been deposited in the DDBJ/ENA/GenBank (accession no. RHFM00000000 for Klebsiella pneumoniae OT1 and accession no. RHFN00000000 for Kluyvera ascorbata OT2). The versions described in this article are versions RHFM01000000 and RHFN01000000.

This clinical case highlights the possibility of plasmid-mediated horizontal transfer between species during infections. Furthermore, KPC-2–producing K. ascorbata has only been isolated once, from a rectal swab in a surveillance study in IsraelReference Geffen, Adler and Paikin12 and once in China from a patient’s biliary drainage.Reference Wang, Jing, Lai, An and Yang13 We suggest that the carbapenem-susceptible K. ascorbata recovered in the fourth CT-guided drainage procedure could be related to a different clone or a heteroresistance event, but we cannot confirm this hypothesis. As far as we know, this is the first report of a KPC-2–carrying plasmid transference from a multidrug-resistant Klebsiella pneumoniae ST 437 to a Kluyvera ascorbata during abdominal infection.

Author ORCIDs

Otávio Hallal Ferreira Raro, 0000-0001-7374-0788

Acknowledgments

We thank the support (finance code - 001) and the PhD scholarship (code - 1794919) offered by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES).

Financial support

This study was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 and by internal funding.

Conflicts of interest

All authors report no conflicts of interest relevant to this article.

References

Ben-David, D, Kordevani, R, Keller, N, et al. Outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Clin Microbiol Infect 2012;18:5460.CrossRefGoogle ScholarPubMed
Patel, G, Huprikar, S, Factor, SH, Jenkins, SG, Calfee, DP. Outcomes of carbapenem-resistant infection and the impact of Klebsiella pneumoniae antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29:10991106.CrossRefGoogle ScholarPubMed
Pitout, JDD, Nordmann, P, Poirel, L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 2015;59:58735884.CrossRefGoogle ScholarPubMed
Porreca, AM, Sullivan, KV, Gallagher, JC. The epidemiology, evolution, and treatment of KPC-producing organisms. Curr Infect Dis Rep 2018;20:13.CrossRefGoogle ScholarPubMed
Farmer, JJ, Fanning, GR, Huntley-Carter, GP, et al. Kluyvera, a new (redefined) genus in the family Enterobacteriaceae: identification of Kluyvera ascorbata sp. nov. and Kluyvera cryocrescens sp. nov. in clinical specimens. J Clin Microbiol 1981;13:919933.Google ScholarPubMed
Carter, JE, Evans, TN. Clinically significant Kluyvera infections. Am J Clin Pathol 2005;123:334338.CrossRefGoogle ScholarPubMed
Thele, R, Gumpert, H, Christensen, LB, et al. Draft genome sequence of a Kluyvera intermedia isolate from a patient with a pancreatic abscess. J Glob Antimicrob Resist 2017;10:12.CrossRefGoogle ScholarPubMed
Clinical and Laboratory Standards Institute. M100 - Performance Standards for Antimicrobial Susceptibility Testing. Wayne, PA: CLSI; 2018.Google Scholar
Naas, T, Cuzon, G, Truong, H, Nordmann, P. Role of IS Kpn7 and deletions in bla KPC gene expression. Antimicrob Agents Chemother 2012;56:47534759.CrossRefGoogle ScholarPubMed
Fehlberg, LCC, Carvalho, AMC, Campana, EH, Gontijo-Filho, PP, Gales, AC. Emergence of Klebsiella pneumoniae–producing KPC-2 carbapenemase in Paraíba, Northeastern Brazil. Brazilian J Infect Dis 2012;16:577580.CrossRefGoogle ScholarPubMed
Seki, LM, Pereira, PS, Maria da Penh, AH, et al. Molecular epidemiology of KPC-2–producing Klebsiella pneumoniae isolates in Brazil: the predominance of sequence type 437. Diagn Microbiol Infect Dis 2011;70:274–247.CrossRefGoogle ScholarPubMed
Geffen, Y, Adler, A, Paikin, S, et al. Detection of the plasmid-mediated KPC-2 carbapenem-hydrolysing enzyme in three unusual species of the Enterobacteriaceae family in Israel. J Antimicrob Chemother 2013;68:719720.CrossRefGoogle ScholarPubMed
Wang, L, Jing, Y, Lai, K, An, J, Yang, J. A Case of Biliary Tract Infection Caused by KPC-2–producing Kluyvera ascorbata. Case Rep Infect Dis 2018;2018:12.Google ScholarPubMed
Figure 0

Table 1. Antimicrobial Resistance Profile of the Klebsiella pneumoniae and Kluyvera ascorbata Pathogenic Isolates and the Transconjugants TKp and TKa

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