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

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.

Keywords

• bloodstream infections
• recipient
• allogeneic hematopoietic stem cell transplantation
• multiresistant gramnegative bacteria
• colonization
• fluoroquinolones
• neutropenia