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Author Spotlight: Advancing Pathogen Detection and Disease Assessment in Real-Time Using M-ROSE

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Enhancing the Time-to-Positivity Paradigm for Guidance of Antimicrobial Therapy: A Model-Based Approach.

Sowrav Barua¹, James E Smith², Vincent H Tam^1,2

¹Department of Chemical and Biomolecular Engineering, University of Houston Cullen College of Engineering, Houston, TX 77204.

Computers & Chemical Engineering

|November 27, 2025

Summary

Enhanced time to positivity (TTP) uses modified instrumentation and mathematical modeling to guide antimicrobial therapy. This novel approach optimizes treatment by systematically analyzing TTP data for improved clinical outcomes.

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Published on: August 30, 2018

Area of Science:

Clinical microbiology
Infectious disease
Pharmacodynamics

Background:

Time to positivity (TTP) is an empirical diagnostic parameter in blood cultures.
Current TTP use is limited, primarily informing clinicians of infection severity before therapy.
This limits TTP's effectiveness and clinical adoption for treatment optimization.

Purpose of the Study:

To introduce an enhanced TTP approach for systematic antimicrobial therapy design.
To integrate modified TTP instrumentation with novel mathematical modeling.
To provide systematic guidance for antimicrobial therapy using TTP data.

Main Methods:

Modified operation of standard TTP instrumentation.
Novel mathematical modeling using TTP data for therapy guidance.
In vitro evaluation using specific antibiotic combinations against resistant bacteria.

Main Results:

The enhanced TTP approach was evaluated using ceftazidime/avibactam against *Acinetobacter baumannii* and cefiderocol/avibactam against *Pseudomonas aeruginosa*.
Model-based predictions of therapeutic outcomes aligned with experimental results in a hollow fiber infection model.
This study represents the first enhancement of the TTP assay.

Conclusions:

Enhanced TTP systematically informs antimicrobial therapy design.
The approach demonstrated consistency between predicted and experimental outcomes.
Further development could establish enhanced TTP as a tool for optimizing antimicrobial therapy.