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 carefully reviewed the article titled "Time to positivity as a predictor of catheter-related bacteremia and mortality in adults with Pseudomonas aeruginosa bloodstream infection" by Marco et al. [1]. This study provides valuable insights into the role of time to positivity (TTP) and differential time to positivity (DTP) as diagnostic and prognostic markers for catheter-related Pseudomonas aeruginosa (PAE) bloodstream infections (PAE-BSI). While the authors have made significant contributions, there are still several aspects worth further consideration to enhance the applicability of TTP as a diagnostic and prognostic tool in clinical settings.

One area that requires deeper exploration is the potential influence of the microbiological characteristics of Pseudomonas aeruginosa on TTP. Specifically, the resistance profiles of the strains in question could play a significant role in the dynamics of TTP. While the study suggests that TTP correlates with the presence of catheter-related infections, it does not address how different resistance mechanisms in PAE might affect this marker. Strains harboring extended-spectrum beta-lactamases (ESBLs), carbapenemases, or other multidrug-resistant mechanisms may demonstrate delayed or altered growth kinetics compared to susceptible strains [2, 3]. This delay in growth could lead to longer TTP, potentially confounding the predictive value of TTP in diagnosing infections caused by resistant strains. In practice, this variation could be particularly important in settings with a high burden of multidrug-resistant organisms, where clinicians must be cautious in interpreting TTP as a reliable indicator for catheter-related infection. A more granular analysis that examines the relationship between TTP and different resistance patterns, or even molecular subtypes of PAE, would provide a more nuanced understanding of the predictive value of TTP and help optimize antibiotic stewardship strategies.

Another point of concern is the influence of patient factors, particularly comorbidities and immune status, on TTP and its prognostic value. The study acknowledges the role of underlying health conditions but stops short of exploring how specific immunocompromised states might affect TTP. For example, patients with neutropenia, as well as those receiving immunosuppressive therapy (e.g., corticosteroids, biologics, or chemotherapy), may exhibit a prolonged time to positivity due to impaired host immune responses[4]. Moreover, immunosuppressed individuals may also face higher mortality risks regardless of the promptness of diagnosis [5]. Therefore, stratifying the results by immune status or underlying comorbidities could significantly improve the interpretability of TTP as a prognostic marker. Understanding the interaction between these patient-specific factors and TTP could help clinicians better predict outcomes and make more informed decisions regarding treatment intensification or de-escalation.

Lastly, while the study focuses on 30-day mortality, it would be prudent to extend the analysis to include long-term outcomes that could further define the clinical relevance of TTP. Thirty-day mortality is an important metric, but it does not capture the full spectrum of patient outcomes, especially for those who survive beyond the acute phase. For example, long-term complications such as recurrent infections, development of chronic organ dysfunction (e.g., renal failure or cardiovascular complications), or the need for prolonged intravenous access are critical in evaluating the overall burden of infection. It would be valuable for future studies to track patients beyond 30 days and investigate how TTP correlates with longer-term survival and quality of life. By integrating long-term outcome data, the prognostic implications of TTP could be more clearly understood, helping to refine management strategies and improve post-acute care.

In conclusion, while the study makes important contributions to the understanding of TTP as a diagnostic and prognostic tool for PAE-BSI, further investigation into the influence of microbial resistance patterns, patient-specific factors such as immune status, and long-term clinical outcomes is necessary. These additional layers of analysis would strengthen the clinical utility of TTP, making it a more robust tool for guiding treatment decisions and improving patient outcomes.

Availability of supporting data

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