Preview

Oncohematology

Advanced search

Risk of bloodstream infections in allogeneic hematopoietic cell transplant recipients according to gut mucosal colonization and fluoroquinolone implementation during neutropenia

https://doi.org/10.17650/1818-8346-2023-18-1-88-100

Abstract

Background. Higher rate of gram-negative bloodstream infections (BSI) have been recently documented from transplantation centers providing fluoroquinolone (FQ) prophylaxis.
Aim. To define the incidence of BSI during neutropenia according to gut mucosal colonization with resistant gramnegative bacteria and FQ administration.
Materials and methods. Of 284 allogeneic hematopoietic cell transplant recipients included in the study, 154 (54.2 %) were identified as colonized with resistant gram-negative bacteria, and 130 (45.8 %) patients as non-colonized. Resistant gram-negative bacteria included Enterobacterales with extended spectrum beta-lactamase production, carbapenem-resistant Enterobacterales, Stenotrophomonas maltophilia, and carbapenem-resistant strains of Pseudomonas aeruginosa. Colonized patients did not receive FQ prophylaxis (n = 147) except 7 patients who received FQ as sequential therapy due to residual inflammatory lung lesions. Among non-colonized patients 98 received FQ prophylaxis, whereas 32 did not.
Results. Probability of gram-negative BSI (71.4 %; p <0.0001), and extended spectrum beta-lactamase-producing Enterobacterales BSI (57.1 %; p <0.0001) was significantly higher in colonized patients receiving FQ. No significant difference was found in probability of gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (hazard ratio (HR) 35.32; 95 % confidence interval (CI) 9.15–136.44; p <0.0001) or without FQ (HR 3.44; 95 % CI 1.15–10.31; p = 0.007), omission of FQ in non-colonized patients (HR 4.03; 95 % CI 1.08–15.00; p = 0.038), and active disease before allogeneic hematopoietic cell transplantation (HR 2.17; 95 % CI 1.03–4.63; p = 0.042) were associated with higher risk of gram-negative BSI, whereas mismatched unrelated donor transplantations were associated with higher gram-positive BSI risk (HR 3.84; 95 % CI 1.63–9.08; p = 0,009).
Conclusion. Colonization with multiresistant gram-negative bacteria is a predictor of gram-negative BSI, including multiresistant pathogens, especially when FQ are prescribed during neutropenia, while in non-colonized patients FQ prophylaxis is an effective approach significantly reducing gram-negative BSI.

About the Authors

G. A. Klyasova
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

Galina Aleksandrovna Klyasova

125167, Moscow, Novyy Zykovskiy Proezd, 4



M. I. Akhmedov
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



L. A. Kuzmina
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



A. V. Fedorova
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



D. A. Mironova
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



E. N. Parovichnikova
National Medical Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



References

1. Mikulska M., Averbuch D., Tissot F. et al. Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect 2018;76(1):20–37. DOI:10.1016/j.jinf.2017.10.009

2. Egan G., Robinson P.D., Martinez J.P.D. et al. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: a systematic review of randomized trials. Cancer Med 2019;8(10):4536–46. DOI:10.1002/cam4.2395

3. Averbuch D., Tridello G., Hoek J. et al. Antimicrobial resistance in gram-negative rods causing bacteremia in hematopoietic stem cell transplant recipients: intercontinental prospective study of the infectious diseases working party of the European Bone Marrow Transplantation Group. Clin Infect Dis 2017;65(11):1819–28. DOI:10.1093/cid/cix646

4. Satlin M.J., Chavda K.D., Baker T.M. et al. Colonization with levofloxacin-resistant extended-spectrum β-lactamase-producing enterobacteriaceae and risk of bacteremia in hematopoietic stem cell transplant recipients. Clin Infect Dis 2018;67(11):1720–8. DOI:10.1093/cid/ciy363

5. Tsai Y.M., Wang S., Chiu H.C. et al. Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae. BMC Microbiol 2020;20:315. DOI:10.1186/s12866-020-02010-3

6. Klyasova G.A., Okhmat V.A. Antimicrobial therapy. In: Diagnostic algorithms and treatment protocols for diseases of the blood system. Ed.: V.G. Savchenko. Vol. 2. Moscow: Praktika, 2018. Pp. 1067–1114. (In Russ.).

7. Averbuch D., Orasch C., Cordonnier C. 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 2013;98(12):1826–35. DOI:10.3324/haematol.2013.091025

8. Kumar S., Paiva B., Anderson K.C. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17(8):e328–46. DOI:10.1016/S1470-2045(16)30206-6

9. Bacigalupo A., Ballen K., Rizzo D. et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009;15(12):1628–33. DOI:10.1016/j.bbmt.2009.07.004

10. Karanika S., Karantanos T., Arvanitis M. et al. Fecal colonization with extended-spectrum beta-lactamase-producing enterobacteriaceae and risk factors among healthy individuals: a systematic review and metaanalysis. Clin Infect Dis 2016;63(3):310–8. DOI:10.1093/cid/ciw283

11. Liss B.J., Vehreschild J.J., Cornely O.A. et al. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamaseproducing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection 2012;40(6):613–9. DOI:10.1007/s15010-012-0269-y

12. Vehreschild M.J.G.T., Hamprecht A., Peterson L. et al. A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother 2014;69(12):3387–92. DOI:10.1093/jac/dku305

13. Arnan M., Gudiol C., Calatayud L. et al. Risk factors for, and clinical relevance of, faecal extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies. Eur J Clin Microbiol Infect Dis 2011;30(3):355–60. DOI:10.1007/s10096-010-1093-x

14. Andria N., Henig O., Kotler O. et al. Mortality burden related to infection with carbapenem-resistant gram-negative bacteria among haematological cancer patients: a retrospective cohort study. J Antimicrob Chemother 2015;70(11):3146–53. DOI:10.1093/jac/dkv218

15. Jaiswal S.R., Gupta S., Kumar R.S. et al. Gut colonization with carbapenem-resistant enterobacteriaceae adversely impacts the outcome in patients with hematological malignancies: results of a prospective surveillance study. Mediterr J Hematol Infect Dis 2018;10(1):e2018025. DOI:10.4084/MJHID.2018.025

16. Akhmedov M., Klyasova G., Kuzmina L. et al. Incidence, etiology, risk factors and outcomes of pre-engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation. Transpl Infect Dis 2022;24(3):e13842. DOI:10.1111/tid.13842

17. Satlin M.J., Chen L., Douglass C. et al. Colonization with fluoroquinolone-resistant enterobacterales decreases the effectiveness of fluoroquinolone prophylaxis in hematopoietic cell transplant recipients. Clin Infect Dis 2021;73(7):1257–65. DOI:10.1093/cid/ciab404

18. Averbuch D., Tridello G., Hoek J. et al. Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality. J Infect 2020;81(6):882–94. DOI:10.1016/j.jinf.2020.11.002


Review

For citations:


Klyasova G.A., Akhmedov M.I., Kuzmina L.A., Fedorova A.V., Mironova D.A., Parovichnikova E.N. Risk of bloodstream infections in allogeneic hematopoietic cell transplant recipients according to gut mucosal colonization and fluoroquinolone implementation during neutropenia. Oncohematology. 2023;18(1):88-100. (In Russ.) https://doi.org/10.17650/1818-8346-2023-18-1-88-100

Views: 8366


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1818-8346 (Print)
ISSN 2413-4023 (Online)