Pros and cons of using biomarkers versus clinical decisions in start and stop decisions for antibiotics in the critical care setting

Intensive Care Med. 2015 Oct;41(10):1739-51. doi: 10.1007/s00134-015-3978-8. Epub 2015 Jul 21.


Introduction: Patients in the intensive care unit (ICU) frequently receive prolonged or even unnecessary antibiotic therapy, which selects for antibiotic-resistant bacteria. Over the last decade there has been great interest in biomarkers, particularly procalcitonin, to reduce antibiotic exposure.

Methods: In this narrative review, we discuss the value of biomarkers and provide additional information beyond clinical evaluation in order to be clinically useful and review the literature on sepsis biomarkers outside the neonatal period. Both benefits and limitations of biomarkers for clinical decision-making are reviewed.

Results: Several randomized controlled trials (RCTs) have shown the safety and efficacy of procalcitonin to discontinue antibiotic therapy in patients with severe sepsis or septic shock. In contrast, there is limited utility of procalcitonin for treatment initiation or withholding therapy initially. In addition, an algorithm using procalcitonin for treatment escalation has been ineffective and is probably associated with poorer outcomes. Little data from interventional studies are available for other biomarkers for antibiotic stewardship, except for C-reactive protein (CRP), which was recently found to be similarly effective and safe as procalcitonin in a randomized controlled trial. We finally briefly discuss biomarker-unrelated approaches to reduce antibiotic duration in the ICU, which have shown that even without biomarker guidance, most patients with sepsis can be treated with relatively short antibiotic courses of approximately 7 days.

Conclusions: In summary, there is an ongoing unmet need for biomarkers which can reliably and early on identify patients who require antibiotic therapy, distinguish between responders and non-responders and help to optimize antibiotic treatment decisions among critically ill patients. Available evidence needs to be better incorporated in clinical decision-making.

Keywords: Antibiotic stewardship; CRP; Procalcitonin; Respiratory tract infections; Sepsis; Short-course therapy.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Biomarkers / blood*
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Critical Care / methods*
  • Critical Illness / therapy*
  • Decision Making
  • Humans
  • Predictive Value of Tests*
  • Protein Precursors / blood*
  • Randomized Controlled Trials as Topic
  • Shock, Septic / drug therapy*


  • Anti-Bacterial Agents
  • Biomarkers
  • CALCA protein, human
  • Protein Precursors
  • Calcitonin
  • Calcitonin Gene-Related Peptide