Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Procalcitonin as a compass for antibiotic decisions in pneumonia

  Procalcitonin has become one of the most useful blood biomarkers for distinguishing bacterial infection from other causes of systemic inflammation. In pneumonia, where the decision to start, continue, or stop antibiotics is often difficult, a reliable signal adds considerable value to bedside assessment.

  Australian clinicians navigate this dilemma daily. Across emergency departments in Sydney, Melbourne, Brisbane, and Perth, patients arrive with cough, fever, and chest-imaging changes that may be viral, bacterial, or a mixed picture. Per-capita antibiotic use in Australia remains above the OECD median, and antimicrobial stewardship programs have worked for years to bring prescribing closer to the evidence base.

  Procalcitonin-guided antibiotic stewardship offers a structured way to address this gap. By tracking serial concentrations, clinicians can shorten treatment courses, avoid unnecessary prescriptions, and ease pressure on the Pharmaceutical Benefits Scheme, which subsidises most of the agents in question.

  The supporting evidence has matured over the past two decades. From large European multicentre trials to local Australian implementation studies, the data now permit specific recommendations for hospitals and intensive care units treating pneumonia.

  Procalcitonin in the inflammatory landscape

  Procalcitonin is the pro-hormone of calcitonin and is produced by thyroid parafollicular cells as well as by neuroendocrine cells in the lung and intestine. In healthy people, circulating concentrations are below 0.05 µg/L. When bacterial endotoxins or pro-inflammatory cytokines stimulate the host response, synthesis switches on within three to six hours and peaks at twelve to twenty-four hours.

  Viral infections suppress procalcitonin release through interferon-gamma, which is why concentrations often remain low in purely viral respiratory illness. This kinetic profile gives procalcitonin an edge over C-reactive protein, which can climb with any inflammatory stimulus, and over the white cell count, which is influenced by stress, steroids, and haematological disease.

  The biomarker is not perfect. It can rise after major surgery, severe trauma, burns, or in patients with reduced renal clearance. Recognition of these confounders is essential before a procalcitonin value is used to justify withholding or stopping antibiotics.

  Trials that shaped current practice

  The ProHOSP trial in 2009 randomised more than 1,300 Swiss patients with lower respiratory tract infections to procalcitonin-guided care or standard guidelines. The intervention group received shorter courses, with median antibiotic exposure falling by roughly a third, and there was no signal of increased mortality or treatment failure.

  The French ProRATA trial extended the concept to intensive care. In 621 ICU patients, the procalcitonin protocol was associated with a 2.7-day reduction in antibiotic duration and a small drop in multi-drug-resistant organism isolation at 28 days.

  More recent meta-analyses pooling results from over twenty trials report consistent reductions in antibiotic exposure of two to four days across community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. None of these syntheses has shown excess mortality, and several suggest a lower risk of treatment-related adverse events.

  Adapting protocols to the Australian setting

  Assays cleared by the Therapeutic Goods Administration are widely available in Australian pathology networks, including the Brahms Kryptor and Diazyme platforms used at sites such as Royal Prince Alfred in Sydney, The Alfred in Melbourne, and Fiona Stanley Hospital in Perth. Turn-around times of under an hour now make twice-daily monitoring practical on general medical wards.

  Reference cut-offs developed overseas have been validated locally. A concentration below 0.1 µg/L generally argues against bacterial infection, 0.1 to 0.25 µg/L falls into a grey zone requiring clinical judgement, and values above 0.25 to 0.5 µg/L support continuing or starting antibiotics. These thresholds are usually embedded directly into electronic medication management systems so that prescribers see an alert when an order falls outside the suggested range.

  Antimicrobial stewardship committees in major tertiary centres have begun to adopt procalcitonin-guided protocols as part of broader programs aimed at meeting the requirements of the National Safety and Quality Health Service Standards. The Australian Commission on Safety and Quality in Health Care has endorsed antimicrobial stewardship as a mandatory element of hospital accreditation, giving local committees a clear mandate to pilot such biomarkers.

  Procalcitonin thresholds in suspected pneumonia:

  • Below 0.1 µg/L: bacterial infection unlikely, antibiotics usually withheld
  • 0.1 to 0.25 µg/L: indeterminate, repeat testing and clinical review recommended
  • 0.25 to 0.5 µg/L: bacterial infection likely, antibiotics encouraged
  • Above 0.5 µg/L: strong evidence of bacterial infection, full course indicated

  Special populations and co-management

  Indigenous Australians experience disproportionately high rates of community-acquired pneumonia, and remote communities often present late in the illness. Where pathology services are limited, point-of-care procalcitonin devices are being trialled to support earlier triage and safer antibiotic decisions.

  Smoking remains a leading modifiable risk factor for bacterial pneumonia, and current smokers gain particular benefit from targeted support during an admission. Pairing procalcitonin-guided antibiotic discontinuation with structured smoking cessation in hospitals creates a combined stewardship and preventive package that has shown promise in pilot programs across New South Wales and Victoria.

  In intensive care, patients with ventilator-associated pneumonia often receive prolonged broad-spectrum courses. Serial procalcitonin measurement allows clinicians to step down or stop therapy when concentrations fall by 80 percent or more from the peak, an approach now incorporated into several Australian ICU guidelines.

  When the signal is less reliable

  Early in the course of infection, before concentrations have risen, a low value can be falsely reassuring. Repeat measurement twelve to twenty-four hours later is the standard response.

  Renal impairment prolongs procalcitonin clearance and can elevate baseline readings. Patients on haemodialysis, those with stage four or five chronic kidney disease, and the elderly may need adjusted cut-offs that some Australian laboratories are now reporting alongside the main result.

  Severe non-infectious stress, including major abdominal surgery, polytrauma, and burns, can drive procalcitonin into the range typical of bacterial infection. In these settings the biomarker should be used as a trend rather than a single threshold.

  Steps to introduce a procalcitonin-guided protocol:

  • Gain endorsement from the hospital antimicrobial stewardship committee
  • Embed cut-off alerts in the electronic prescribing system
  • Provide case-based teaching to junior medical officers and pharmacists
  • Audit compliance and antibiotic days of therapy at six and twelve months

  Run a six-month pilot on one respiratory ward, measure antibiotic days of therapy against the same ward's pre-protocol baseline, and present the results to the local antimicrobial stewardship committee before considering broader rollout.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)