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. IMPORTANCE Several 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.

6.In supplementary table 2, 3, 4, why does the diagnose column different?In table 2, there were ALL and others, and in table 3 and 4, there were AA and others.And the note of AA could not be seen under the table.7. Some formatting of punctuation marks should be corrected.
Reviewer #2 (Comments for the Author): Comments to the Author This study developed a clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allo-HSCT.The prediction model had an area under the curve of 0.775 and 0.846 in the derivation and the validation cohort, respectively.KP colonization negatively effects platelet engraftment and survival after allo-HSCT.My comments are as follows: 1) The variables for the final model were selected using backward stepwise logistic regression.Did the author try multiple algorithms and consider them comprehensively?
2) The author demonstrated that among the patients with KP colonization, 57(34.3%)were colonized with CRKP.Were there differences in "Clinical events and outcomes" between the KP cohort and CRKP cohort?
3) It is recommended that the author revise all baseline tables in the paper to three-line tables.4) The caption (KP-mode, All, and None) of Figure 2 is unclear.5) There are many minor spelling errors in the text.The author needs to comprehensively check and revise them through the whole manuscript.

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The authors performed a single center, retrospective, case-control study and successfully developed a clinical prediction model for KP colonization in allo-HSCT patients.And the study found that Patients with KP colonization had higher NRM, worse PFS, and worse OS within 100 days after allo-HSCT.The study is logical and thorough, but the English language requires upgrading.
I have a few comments below for authors: 1. Line 94, the include variable "previous infection", how long before the KP colonization was the previous infection included?2. Line 149 mentioned that 54 (2.6%) patients were colonized with CRKP isolates, did the author study the NRM, PFS and OS in CRKP colonized patients?Does there have any significant difference between patients colonized with CRKP an CSKP isolates?
3. Line 241-242, the author mentioned that high-risk patients could be treated with empiric antibiotics during the peri-transplantation period.Does this mean the decolonization therapy?Could the author list some support references? 4. In the abstract, the author mentioned that anal swab was taken, but in main text, the method mentioned rectal swab.So, it should be clear which method was taken. 5. Line 60, the first KP in the main text should be full name.
6.In supplementary table 2, 3, 4, why does the diagnose column different?In table 2, there were ALL and others, and in table 3 and 4, there were AA and others.And the note of AA could not be seen under the table.