Time course of oral aerobic microbiota in the patients after intensive chemotherapy and hematopoietic stem cell transplantation

Authors

  • A.A. Spiridonova 1, head of the Clinical microbiology Department
    ORCID ID: 0000-0001-9866-5016
  • A.B. Chukhlovin 1, PhD in Medical Sciences, full professor of the Transplantology Lab
    ORCID ID: 0000-0001-9703-4378
  • I.B. Baranova 1, oral and maxillofacial surgeon of the Consulting and diagnostic Department at the Pediatric oncology, hematology, and transplantology research Institute
    ORCID ID: 0000-0001-5152-8639
  • A.P. Grigoriants 1, PhD in Medical Sciences, associate professor of the Dentistry diseases propaedeutics Department
    ORCID ID: 0000-0001-7518-4279
  • I.N. Antonova 1, PhD in Medical Sciences, full professor of the Dentistry diseases propaedeutics Department, director of the Dentistry and maxillofacial surgery research Institute
    ORCID ID: 0000-0003-2543-6137
  • M.D. Vladovskaya 1, PhD in Medical Sciences, hospital registry chief at Pediatric oncology, hematology, and transplantology research Institute
    ORCID ID: 0000-0002-0215-4623
  • L.S. Zubarovskaya 1, PhD in Medical Sciences, full professor of the Pediatric oncology, hematology, and transplantology
    ORCID ID: 0000-0003-2594-7703
  • B.V. Afanasyev 1, PhD in Medical Sciences, professor of the Hematology, transfusiology and transplantology Department, director of the Pediatric oncology, hematology, and transplantology research Institute
    ORCID ID: 0000-0002-1235-4530
  • 1 Pavlov University, 197022, Saint-Petersburg, Russia

Abstract

There are few data on time course of oral microbiota after intensive chemotherapy and hematopoietic stem transplantation (HSCT). The aim of present study was to evaluate detection frequency of aerobic microorganisms from oral cavity before therapy and within initial 120 days after HSCT.
Materials and methods.
We studied composition and time course of aerobic microbiota in oral cavity (oropharingeal area) in 419 patients aged from 1 to 76 years with, mostly, oncohematological diseases, who underwent intensive chemotherapy with subsequent allogeneic HSCT. Sampling of biological material for routine bacteriological studies was been carried out before chemotherapy and within 120 days after HSCT. Data analysis was performed for 4 age groups: from 1—5 to over 22 years old.
Results.
Positive findings were obtained in 66% of cases after analyzing 1472 cultures. Most common species were as follows: S. viridans, S. epidermidis, Neisseria spp., K. pneumoniae, Corynebacterium spp. Detection rate for K. pneumoniae, like as average number of microbial species per culture was increased in adult patients (over 22 years) as compared to pediatric and young patients. Following intensive therapy and HSCT, pronounced decrease in detection rates was revealed for S. viridans, Corynebacterium spp., Neisseria spp., as well as mean number of microbial associations in cultures within first month after treatment, most probably, due to early effective antibacterial prophylaxis. Meanhile, detection rates of K. pneumoniae from oropharyngeal mucosa did not decrease, followed by significant increase for 2—4 months after HSCT, thus being concordant with later development of infectious complications and evidence of polyresistant Klebsiella strains in other infected sites. Sampling from alveolar sockets was performed in 51 specimens within 0 to 2 months after HSCT showing predominant growth of S. viridans, S. epidermidis, Neisseria, Pseudomonas spp., Klebsiella spp., thus showing no differences from results yielded in other oral samples.
Conclusions.
Combined effect of cytostatic therapy upon immune response, along with antibiotic therapy, was accomplished by transient exhaustion of main classes of oral microbiota. Upon recovery of immune system, selective outgrowth of, most likely, resistant Klebsiella strains is observed. Full-spectrum microbiota analysis after HSCT, including anaerobic organisms, should be studied, e.g., by multiplex PCR or NGS of 16S rRNA gene.

Key words:

oncohematology, chemotherapy, hematopoietic stem cell transplantation, bacterial cultures, oral mucosa, risk factors

For Citation

[1]
Spiridonova A.A., Chukhlovin A.B., Baranova I.B., Grigoriants A.P., Antonova I.N., Vladovskaya M.D., Zubarovskaya L.S., Afanasyev B.V. Time course of oral aerobic microbiota in the patients after intensive chemotherapy and hematopoietic stem cell transplantation. Clinical Dentistry (Russia).  2021; 24 (3): 40—46

References

  1. Hull M.W., Chow A.W. Indigenous microflora and innate immunity of the head and neck. Infect Dis Clin North Am. 2007; 21 (2): 265—82. PMID: 17561071
  2. Hegde M.C., Kumar A., Bhat G., Sreedharan S. Oral Microflora: A Comparative Study in HIV and Normal Patients. Indian J Otolaryngol Head Neck Surg. 2014; 66 (Suppl 1): 126—32. PMID: 24533371
  3. Aas J.A., Paster B.J., Stokes L.N., Olsen I., Dewhirst F.E. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005; 43 (11): 5721—32. PMID: 16272510
  4. Grigoriants A.P., Rabinowitch I.M., Chukhlovin A.B. Stomatological problems and infectious complications after hematopoietic stem cell transplantation. Cellular Therapy and Transplantation. 7 (2): 10—19. DOI: 10.18620/ctt-1866-8836-2018-7-2-10-19
  5. Chukhlovin A.B., Grigoriants A.P. Pathology of oral mucosa after intensive chemoradiotherapy (review). Clinical Dentistry (Russia). 2018; 3 (87): 39—43 (In Russ.). DOI: 10.37988/1811—153X_2018_3_39
  6. Chukhlovin A.B., Pankratova O.S. Opportunistic microflora at unusual sites: marker pathogens in severe posttransplant immune deficiency. Cellular Therapy and Transplantation. 2017; 6 (4): 28—41. DOI: 10.18620/ctt-1866-8836-2017-6-4-28-41
  7. Marena C., Zecca M., Carenini M.L., Bruschi A., Bassi M.L., Olivieri P., Azzaretti S., Locatelli F. Incidence of, and risk factors for, nosocomial infections among hematopoietic stem cell transplantation recipients, with impact on procedure-related mortality. Infect Control Hosp Epidemiol. 2001; 22 (8): 510—7. PMID: 11700879
  8. Laheij A.M.G.A., de Soet J.J., von dem Borne P.A., Kuijper E.J., Kraneveld E.A., Loveren C., Raber-Durlacher J.E. Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients. Support Care Cancer. 2012; 20 (12): 3231—40. PMID: 22531876
  9. Czirók E., Prinz G.Y., Dénes R., Reményi P., Herendi A. Value of surveillance cultures in a bone marrow transplantation unit. J Med Microbiol. 1997; 46 (9): 785—91. PMID: 9291891
  10. Vavilov V.N., Averyanova M.Yu., Bondarenko S.N., Stancheva N.V., Zubarovskaya L.S., Afanasyev B.V. Bacterial infections in the early period after allogeneic bone marrow transplantation. Therapeutic Archive. 2015; 87 (7): 88—93 (In Russ.). eLIBRARY ID: 24251366
  11. Chukhlovin A.B., Spiridonova A.A., Baranova I.B., Grigoriants A.P., Vladovskaya M.D., Zubarovskaya L.S., Afanasyev B.V. Common bacterial cultures from oral mucosa after hematopoietic stem cell transplantation: dependence on the patient characteristics and therapeutic factors. Cellular Therapy and Transplantation. 2019; 8 (4): 49—56. DOI: 10.18620/ctt-1866-8836-2019-8-4-49-56
  12. Bergmann O.J. Alterations in oral microflora and pathogenesis of acute oral infections during remission-induction therapy in patients with acute myeloid leukaemia. Scand J Infect Dis. 1991; 23 (3): 355—66. PMID: 1909053
  13. Jones L.R., Toth B.B., Keene H.J. Effects of total body irradiation on salivary gland function and caries-associated oral microflora in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol. 1992; 73 (6): 670—6. PMID: 1437034
  14. Chukhlovin A.B., Spiridonova A.A., Vladovskaya M.D., Kazantsev I.V., Kozlov A.V., Gevorgyan A.G., Bykova T.A., Zubarovskaya L.S., Afanasyev B.V. Factors of bacteriuria in children and young adults following hematopoietic stem cell transplantation. Pediatric Hematology/Oncology and Immunopathology. 2020; 19 (2): 54—60 (In Russ.). eLIBRARY ID: 43055672
  15. Fritzenwanker M., Imirzalioglu C., Herold S., Wagenlehner F.M., Zimmer K.P., Chakraborty T. Treatment Options for Carbapenem- Resistant Gram-Negative Infections. Dtsch Arztebl Int. 2018; 115 (20—21): 345—52. PMID: 29914612
  16. Chuhlovin A.B., Solov’eva A.M., Matelo S.K., Kobiyasova I.V., Morozova E.B., Hohlacheva A.V., Teplyakov B.G., Sysoev K.A., Konstantinova V.E., Matelo L.N., Totolyan A.A. Microbial markers of periodontal disease and their practical significance in dentistry. Bulletin of Experimental Biology and Medicine. 2007; 144 (10): 427—31 (In Russ.). eLIBRARY ID: 9578485
  17. Pankratova O.S., Chukhlovin A.B., Shiryaev S.N., Eismont Y.A., Vavilov V.N., Zubarovskaya L.S., Afanasyev B.V. Herpesviruses and oral ulcerations in hematopoietic SCT recipients. Bone Marrow Transplant. 2013; 48 (10): 1364—5. PMID: 23686096
  18. Beckman M.F., Morton D.S., Mougeot F.B., Mougeot J-L.C. Allogenic stem cell transplant-associated acute graft versus host disease: a computational drug discovery text mining approach using oral and gut microbiome signatures. Support Care Cancer. 2021; 29 (4): 1765—79. PMID: 33094358
  19. Blijlevens N.M., Donnelly J.P., De Pauw B.E. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant. 2000; 25 (12): 1269—78. PMID: 10871732
  20. Weber D., Jenq R.R., Peled J.U., Taur Y., Hiergeist A., Koestler J., Dettmer K., Weber M., Wolff D., Hahn J., Pamer E.G., Herr W., Gessner A., Oefner P.J., Brink M.R.M., Holler E. Microbiota disruption induced by early use of broad-spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2017; 23 (5): 845—52. PMID: 28232086
  21. Goloshchapov O.V., Kucher M.A., Chukhlovin A.B. Gut microbiome in hematopoietic stem cell transplantation: patient- and treatment-related factors. Cell Ther Transplant. — 2018; 7 (4): 16—28. DOI: 10.18620/ctt-1866-8836-2018-7-4-16-28

Received

December 1, 2020

Accepted

July 16, 2021

Published on

September 1, 2021