Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

Hermes Ryoiti Higashino; Ana Paula Marchi; Roberta Cristina Ruedas Martins; Laina Bubach Carvalho; Lauro Vieira Perdigão Neto; Marina Farrel Côrtes; Fernando Nivaldo de Oliveira; Edson Luiz Tarsia Duarte; Thais Guimaraes; Flavia Rossi; Aliana M. Ferreira; Vanderson Rocha; Silvia Figueiredo Costa

doi:10.1099/jmm.0.001422

Volume 70, Issue 10

Short Communication

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

Hermes Ryoiti Higashino¹, Ana Paula Marchi², Roberta Cristina Ruedas Martins², Laina Bubach Carvalho³, Lauro Vieira Perdigão Neto^2,4, Marina Farrel Côrtes², Fernando Nivaldo de Oliveira², Edson Luiz Tarsia Duarte¹, Thais Guimaraes³, Flavia Rossi⁴, Aliana M. Ferreira⁵, Vanderson Rocha⁵ and Silvia Figueiredo Costa^1,2
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Affiliations: ¹ Departamento de Doenças Infecciosas e Parasitarias, Hospital das Clínicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil ² Laboratório de Investigação Médica em Protozoologia, Bacteriologia e Resistência Antimicrobiana – LIM/49, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil ³ Comissão de Controle de Infecção Hospitalar do Hospital das Clínicas HCFMUSP, São Paulo, Brazil ⁴ Departmento de Patologia, Divisão de Microbiologia do Laboratório Central - LIM/03, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil ⁵ Departmento de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
*Correspondence: Silvia Figueiredo Costa, [email protected]
Published: 19 October 2021 https://doi.org/10.1099/jmm.0.001422

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml−1. Demographic and clinical data were retrieved from the patients’ charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

Received: 22/01/2021
Accepted: 17/08/2021
Published Online: 19/10/2021

Keyword(s): Carbapenem-resistant Enterobacterales , haematopoietic stem-cell transplantation , Klebsiella infection and survival

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References

Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica Ferrata Storti Foundation 2013; 98:1826–1835
[Google Scholar]
Logan LK, Weinstein RA. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J Infect Dis 2017; 215:S28–36 [View Article]
[Google Scholar]
Tacconelli E, Cataldo MA, Dancer SJ, De Angelis G, Falcone M et al. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients. Clin Microbiol Infect 2014; 20:1–55 [View Article] [PubMed]
[Google Scholar]
Girmenia C, Rossolini GM, Piciocchi A, Bertaina A, Pisapia G et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant 2015; 50:282–288 [View Article] [PubMed]
[Google Scholar]
Mendes ET, Ranzani OT, Marchi AP, Silva MT da, Filho JUA et al. Chlorhexidine bathing for the prevention of colonization and infection with multidrug-resistant microorganisms in a hematopoietic stem cell transplantation unit over a 9-year period: Impact on chlorhexidine susceptibility. Medicine (Baltimore) 2016; 95:e5271 [View Article] [PubMed]
[Google Scholar]
Higashino HR, Marchi AP, Martins RCR, Batista MV, Perdigão Neto LV et al. Colistin-resistant Klebsiella pneumoniae co-harboring KPC and MCR-1 in a hematopoietic stem cell transplantation unit. Bone Marrow Transplant 2019; 54:1118–1120 [View Article] [PubMed]
[Google Scholar]
Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 2019; 47:D687–92 [View Article] [PubMed]
[Google Scholar]
Bertels F, Silander OK, Pachkov M, Rainey PB, van Nimwegen E. Automated reconstruction of whole-genome phylogenies from short-sequence reads. Mol Biol Evol 2014; 31:1077–1088 [View Article] [PubMed]
[Google Scholar]
Galtier N, Gouy M, Gautier C. SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny. Comput Appl Biosci 1996; 12:543–548 [View Article] [PubMed]
[Google Scholar]
Cattaneo C, Di Blasi R, Skert C, Candoni A, Martino B et al. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria. Ann Hematol 2018; 97:1717–1726 [View Article] [PubMed]
[Google Scholar]
Andrey DO, Pereira Dantas P, Martins WBS, Marques De Carvalho F, Almeida LGP et al. An emerging clone, Klebsiellapneumoniae carbapenemase 2-producing K. pneumoniae sequence type 16, associated with high mortality rates in a CC258-endemic setting. Clin Infect Dis 2020; 71:e141–e150 [View Article] [PubMed]
[Google Scholar]
Cienfuegos-Gallet AV, Ocampo de Los Ríos AM, Sierra Viana P, Ramirez Brinez F, Restrepo Castro C et al. Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: A case-control and cohort study. BMC Infect Dis 2019; 19:830 [View Article] [PubMed]
[Google Scholar]

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Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

J. Med. Microbiol. 70, 001422 (2021); https://doi.org/10.1099/jmm.0.001422

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Volume 70, Issue 10

Short Communication

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

Abstract

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