Further considerations on the clinical applicability of time to positivity as a prognostic tool for catheter-related Pseudomonas aeruginosa bloodstream infections

To the Editor,

We appreciate the thoughtful comments by Liao et al. [1] regarding our study [2] on “Time to positivity (TTP) as a predictor of catheter-related bacteremia and mortality in Pseudomonas aeruginosa bloodstream infections (PAE-BSI)”. Their insights highlight important aspects that warrant further discussion, particularly regarding additional variables that could influence the TTP, and about long-term outcome.

In response to the first point, we acknowledge the potential influence of resistance on TTP. We found that susceptible P. aeruginosa strains had a significantly shorter TTP (Table 1). Moreover, this property was consistent across all antibiotic families. Since no clinically relevant TTP cut-off for predicting resistance was identified, this data was not included in the main article due to length limitation. This finding supports that resistant strains may decelerate their replication rates because resistance mechanisms affect one or more metabolic pathways involved in bacterial replication. A previous study in Staphylococcus aureus bacteremia also demonstrated shorter TTP for methicillin-susceptible strains compared to methicillin-resistant ones [3]. However, we have to recognize that other studies focused in Enterobacterales and other non-fermenting gram-negative bacilli have shown contradictory results [4, 5].

Table 1 Factors associated with shorter TTP. Univariate and multivariate analysis.

The authors raise another point regarding immune suppression and comorbidities as potential modifiers of TTP. Although the role of host immunity seems reasonable, our data (Table 1) did not support this statement. In the univariable analysis, chronic kidney disease (CKD) in hemodialysis, neutropenia and corticosteroid therapy were significantly associated with shorter TTP. However, no one was finally included in the multivariable analysis. In the case of CKD in hemodialysis the reason to be excluded is that the majority of these cases were catheter-related bacteremia that is a significant determinant of shorter TTP. Neutropenia reduces the host capacity to clear bacteria from infected tissue resulting in higher bacterial loads in the bloodstream and corticosteroid therapy impair the reticuloendothelial system located at the liver and the spleen, both responsible of rapid bacterial clearance from the blood [6, 7]. Therefore, weak immune system increases the inoculum at the infectious foci and that is the variable superior in the multivariable analysis. According to our findings, we have summarized the main determinants of TTP in Fig. 1.

Fig. 1

Diagram displaying the main determinants of time to positivity (TTP). The figure also represents the microbiological and clinical variables which in turn affect the two main determinants

While we agree that evaluating long-term mortality and post-infection complications would provide a more comprehensive perspective, this was not the primary scope of our study, and this information was not captured in our database.