How to apply biomarkers to optimize antibiotic utilization in hospital-acquired pneumonia?

Decades of biomarker research in sepsis have not translated into consistent changes in practice for hospital-acquired pneumonia (HAP). HAP remains among the most consequential healthcare-associated infections, contributing substantially to morbidity, mortality, and antimicrobial pressure in hospitalized patients. Its management is complicated by diagnostic imprecision and by pathogen heterogeneity, including a disproportionate burden of multidrug-resistant organisms. In this clinical setting, biomarkers have been introduced in clinical practice as adjunctive tools to support diagnostic frameworks and antibiotic stewardship, yet their integration into routine care remains variable and their limitations are frequently underappreciated. Moreover, most of the supporting evidence derives from ventilator-associated pneumonia (VAP), severe community-acquired pneumonia, or mixed sepsis populations, whereas most HAP occurs in non-ventilated patients, in whom biomarker-guided strategies remain largely unstudied. This narrative review argues that the clinical value of procalcitonin and C-reactive protein in HAP lies not in point-in-time diagnosis but in serial kinetic monitoring. We further argue that the value of biomarker-guided treatment-duration strategies specifically is context-dependent, diminishing as baseline antibiotic prescribing improves. We examine the evidence across the full spectrum of HAP management, diagnostic adjunction, treatment monitoring, de-escalation, and discontinuation, applying a clinical function-based framework derived from the NIH/FDA BEST taxonomy. We critically appraise the conditions under which biomarker guidance adds clinical value, specifically where empirical antibiotic courses are prolonged beyond recommended standards, and the contexts in which it does not. We critically appraise landmark trials, including PASS and ADAPT-SEPSIS, where biomarker-guided strategies paradoxically increased antibiotic exposure or failed to outperform already-adequate standard care, and contrast these with kinetic-guided discontinuation protocols, including double-trigger models embedded within digital clinical decision support, that meaningfully shortened treatment without compromising safety. The central message is not a dismissal of biomarkers but a conditional endorsement: their benefit depends on baseline prescribing habits, kinetic rather than threshold-based interpretation, and integration with clinical trajectory rather than substitution for it. Whether these principles extend to non-ventilated HAP requires dedicated evaluation. The immediate clinical priority is not measuring existing biomarkers less often but interpreting and integrating them more correctly within the clinical trajectory.