A clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allogeneic hematopoietic stem cell transplantation

Abstract

The purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723-0.828) in the derivation cohort and 0.846 (95% CI: 0.790-0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.

Keywords: Klebsiella pneumoniae; bloodstream infections; colonization; hematopoietic stem cell transplantation; predictive model.

Fig 1

Patients' enrollment and exclusion of our study.

Fig 2

The plots of pre-allo-HSCT KP colonization predictive model. Calibration plot of clinical model for predicting KP colonization of the derivation cohort (A) and the validation cohort (B). Receiver-operating characteristic curve of the derivation cohort. The AUC was 0.775 (95% CI, 0.723–0.828) (C). Receiver-operating characteristic curve of the validation cohort. The AUC was 0.846 (95% CI, 0.790–0.902) (D). Decision curve analysis of the derivation cohort (E) and validation cohort (F).

Fig 3

Post-transplantation complications within 100 days post-allo-HSCT of KP-colonization group and non-colonization group. Time of neutrophil engraftment was not significantly longer in patients with KP colonization (P = 0.39) (A). Time of platelet engraftment was significantly longer in patients with KP colonization (P < 0.001) (B). The cumulative incidence of KP-BSI was significantly higher in patients with KP colonization (P < 0.001) (C). The cumulative incidence of aGVHD was not significantly higher in patients with KP colonization (P = 0.52) (D). The cumulative incidence of CMV reactivation was not significantly higher in patients with KP colonization (P = 0.71) (E). The cumulative incidence of EBV reactivation was not significantly higher in patients with KP colonization (P = 0.75) (F).

Fig 4

Outcomes within 100 days post-allo-HSCT of recipients in KP-colonization group and non-colonization group. Relapse was not significantly higher in patients with KP colonization (P = 0.28) (A); NRM was significantly higher in patients with KP colonization (P = 0.0031) (B); PFS was significantly lower in patients with KP colonization (P < 0.001) (C); OS was significantly lower in patients with KP colonization (P = 0.013) (D).