Reduction in antibiotic use through procalcitonin testing in patients in the medical admission unit or intensive care unit with suspicion of infection

https://doi.org/10.1016/j.jhin.2011.03.018Get rights and content

Summary

We report an evaluation of the utility of serum procalcitonin (PCT) measurement as an additional diagnostic tool to support initiating or withholding antibiotics in clinical situations where there is a clinical suspicion of infection but the diagnosis is uncertain. During a six-month period, 99 patients on the medical admission unit (MAU) with suspected infection, and 42 patients on the intensive care unit (ICU) with clinical signs or physiological parameters suggesting possible new infection, had serum PCT concentration measured with the result available within 90 min of the request. The test was initiated by the microbiology/infection team during clinical consultations to support the antibiotic decision. On the basis of low PCT values, antibiotics were withheld in MAU on 52 occasions and in ICU on 42 occasions. Patients were followed up prospectively for a week. There was neither progression of bacterial infection requiring antibiotics, nor complications or infection-related mortality in any patients who were denied antibiotics on either MAU or ICU. Without the PCT value it is likely that all of these patients would have received empirical antibiotics. Reduction in unnecessary antibiotic usage was made without any adverse effects on these patients and there was a clear reduction in antibiotic prescribing with cost reduction implications. PCT has the potential to become a valuable tool in antibiotic management.

Introduction

The diagnosis and appropriate treatment of infection can be a huge challenge. Clinical signs and laboratory findings may be subtle in the early stages of infection. In the case of sepsis, multiple organ failure may already have occurred by the time the diagnosis is made and by this stage mortality is considerably greater.1, 2 Hence there is almost certainly considerable overprescribing of empirical antibiotics at the point when the presence of bacterial infection is a diagnostic uncertainty. This has cost implications but more importantly represents a significant burden of antibiotic pressure on the bacterial ecology. Sepsis is defined as systemic inflammatory response syndrome (SIRS) caused by infectious agents. Despite advances in medical technology and clinical care, mortality rates in sepsis remain high.3 Non-infectious factors such as trauma, haemorrhage, pancreatitis, collagen vascular disease or malignancy may be responsible for SIRS, and surgery can result in a similar clinical presentation leading to diagnostic difficulty and uncertainty whether to commence antibiotic treatment.1, 2, 4, 5 Early diagnosis of infection and the prompt initiation of adequate antimicrobial therapy are important for successful outcome. Diagnostic challenges and the lack of specific early markers of infection can lead to withholding or delaying antimicrobial treatment in critically ill patients, or conversely unnecessary antimicrobial treatment in others. In less seriously ill patients presenting as emergencies to medical units, similar diagnostic challenges present themselves. It is not always apparent whether the clinical signs are manifestations of infection or some other pathological process. Common examples of this are crackles heard on auscultation of the chest and distinguishing between an infective or cardiac cause, or whether confusion in an acutely ill elderly patient is the result of infection or some other cause. There is a tendency among many clinicians to treat for infection if in doubt, just in case the cause is infective. This leads in turn to inappropriate antibiotic use, higher costs and so-called ‘collateral damage’ from antibiotics.

Better biomarkers for diagnosing infection would improve the appropriateness of antibiotic use.6 Recently, PCT has been found to have an important role in the diagnosis of bacterial infection.7 PCT is a prohormone of calcitonin, normally produced by thyroid gland C-cells in response to hypocalcaemia. Under normal conditions, very low concentrations of PCT in serum (<0.1 μg/L) are observed.8 In infection, the inflammatory process induces extra-thyroid production of PCT, levels of which increase after 3–4 h, peaking at around 6 h with a plateau of up to 24 h.9 Multiple studies have established the utility of PCT in detecting bacterial infection and different cut-off values have been proposed for different clinical conditions.10, 11, 12, 13, 14, 15, 16 PCT might also accurately differentiate between systemic bacterial infection and non-infectious states.17 However, not all studies have recognised this differentiation.18, 19, 20

The primary aim of this evaluation was to determine the effect of implementing rapid PCT measurement to guide antibiotic therapy in two groups of patients: medical admission unit (MAU) patients and patients on the intensive care unit (ICU) in a UK health setting. To our knowledge, PCT has not been previously evaluated in this setting. A secondary aim was to establish the effect of this approach on reduction of antibiotic usage and potential collateral damage.

Section snippets

Methods

The Royal Hampshire County Hospital in Winchester is a general hospital with around 400 acute beds covering all main specialties. The MAU is a 26-bedded ward and the ICU has ten critical care beds. This evaluation aimed to assess the value of serum PCT measurements as a complementary biomarker to assist decisions regarding antibiotic therapy in MAU and ICU patients. PCT measurement was being evaluated in the microbiology laboratory as a rapid diagnostic test. Since it was being offered

Results

From May to November 2009, 99 PCT tests were performed on 99 MAU patients whose average age was 71 years. PCT value aided the antimicrobial management in 85 of these (Table I). In 33 cases (39%), PCT above the cut-off supported a decision to commence antibiotic therapy. PCT below the cut-off resulted in withholding or stopping antibiotics in 52 cases (61%). In the seven-day follow-up period none of the cases in whom antibiotics were withheld or discontinued required antibiotics on clinical

Discussion

This evaluation demonstrates that there is a role for PCT testing in supporting clinical assessment and antibiotic decision-making. In this group of patients with a suspicion of infection, PCT has been highly discriminatory in separating patients who require antibiotics from those in whom antibiotics contribute little to the clinical course. In no case in either MAU or ICU did withholding antibiotics as a result of a low serum PCT compromise patient outcome. Many of these patients would have

Acknowledgements

We would like to thank colleagues on the intensive care unit, medical admission unit, the microbiology department and N. Parker at the Royal Hampshire County Hospital.

References (31)

  • B. Canan et al.

    Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit

    Crit Care

    (2003)
  • E. Volante et al.

    Early diagnosis of bacterial infection in the neonate

    J Matern Fetal Neonatal Med

    (2004)
  • M. Dryden et al.

    Antibiotics for community-acquired pneumonia

    J Antimicrob Chemother

    (2009)
  • J. Whicher et al.

    Procalcitonin as an acute phase marker

    Ann Clin Biochem

    (2001)
  • P. Dandona et al.

    Procalcitonin increase after endotoxin injection in normal subjects

    J Clin Endocrinol Metab

    (1994)
  • Cited by (28)

    • Procalcitonin levels predict infectious complications and response to treatment in patients undergoing cytoreductive surgery for peritoneal malignancy

      2016, European Journal of Surgical Oncology
      Citation Excerpt :

      Studies have shown that the use of PCT can significantly reduce unnecessary antibiotic use by identifying patients with non-infective (bacterial) aetiologies allowing the early cessation of antibiotics.21 There is a body of controlled studies,13–20,22 mostly in medical patients, that support the role of PCT in diagnosing bacterial infections as a useful antimicrobial stewardship tool. Current evidence relating to the use of PCT measurements in surgical patients is limited but encouraging and, in the main, demonstrates that there is a transient “physiologic” PCT rise following surgery in general,11,23–26 though, the available evidence also suggests that PCT is a more accurate predictor of major anastomotic leak after elective colorectal resection than WCC and CRP.27

    • Role of procalcitonin in managing adult patients with respiratory tract infections

      2012, Chest
      Citation Excerpt :

      An individual patient data meta-analysis focusing on different patient-relevant outcomes and using standardized outcome definitions across trials, and predefined sensitivity and subgroup analyses is currently under way and should shed more light on these issues.71,72 In addition to the randomized trials mentioned here, different studies evaluating PCT in “real life” and outside of study conditions found reductions in antibiotic usage without an apparent increase in adverse outcomes.73,74 Although further study of PCT in respiratory infections is warranted, it seems reasonable to begin using it clinically, based on the more robust areas of data summarized here.

    • Development of quality indicators for antimicrobial stewardship in Belgian hospitals: a RAND–modified Delphi procedure

      2023, Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine
    View all citing articles on Scopus
    View full text