Until now, deciding whether antibiotics are needed for treating a respiratory tract infection has seemed to be more art than science: for evidence of this, one only has to look at the vast differences in prescribing habits of doctors around Europe.
Respiratory infections are extremely common. Doctors are taught to prescribe antibiotics on the basis of clinical features such as pus in the sputum or high fever, which point to the presence of a bacterial pathogen. However, basing this decision on clinical judgment alone is not always easy. Additional lab tests for markers such as C-reactive protein may help to distinguish between a viral and a bacterial infection.
Antibiotic prescriptions not only impose a burden on healthcare resources but, more importantly, contribute to the worldwide problem of antimicrobial resistance. Varying patterns of antibiotic resistance around Europe are strongly linked to differing prescription habits in general practice. Standardised strategies to help reduce antibiotic misuse are desperately needed.
A relatively new marker of bacterial infections, procalcitonin (PCT), may enrich the diagnostic tools of primary care physicians and become a useful part of the decision process.
PCT is a precursor of the hormone calcitonin, which, along with parathyroid hormone, regulates the calcium and phosphate balance in the body. In healthy people, concentrations of PCT are low, since it is produced only in the thyroid gland and is promptly converted to the mature hormone. In the presence of a bacterial infection, however, PCT is produced by nearly all cell systems and released into the blood circulation. It can be found in high concentrations as early as 3 hours after a bacterial infection, reaching maximum levels after 6-12 hours. In people with viral infections, in contrast, PCT levels increase only marginally or not at all.
To fill or not to fill?
The two-part study included patients diagnosed with an acute respiratory tract infection either upper (e.g. sinusitis, middle ear infection) or lower (e.g. bronchitis or pneumonia). In part 1, researchers documented antibiotic prescription rates, values for blood PCT and the outcome of 702 patients presenting with a respiratory infection to 45 primary care physicians.
In Part 2, researchers compared standard care with a PCT-guided antimicrobial treatment in 550 patients. Patients who were in need of antimicrobial treatment according to the clinical judgment of their general practitioner received a prescription but were asked not to fill it until they were told to do so by phone. The doctors were free to choose the type and dosage of antibiotics.
Antibiotics were recommended for patients with PCT levels over 0.25 ng/mL, a threshold below which a bacterial infection is unlikely. However, primary care physicians were allowed to over-rule the recommendation for clinical reasons. Only one blood sample was required for the measurement of PCT levels.
Patients whose PCT levels did not indicate the need for antibiotic treatment were asked to return the prescription.
Patients were followed up with structured telephone interviews by blinded investigators after 2 weeks and again after 4 weeks. They were asked whether their respiratory tract infection symptoms had persisted, whether their infection impaired their everyday life or leisure activities, and whether they needed to visit the doctor again or needed new or additional antibiotic treatment. They were also questioned about the duration of their treatment, any adverse effects and the possible need for hospitalisation.
According to principal investigator Professor Tobias Welte, head of the Department of Respiratory Medicine at Hannover Medical School (Germany), in daily practice, one in three patients receives an antibiotic for a respiratory infection: "We wanted to show that this number can be cut in half."
After initial clinical evaluation, 84 patients (30.5%) were assigned to antibiotics in the PCT group and 89 patients (32.4%) in the control group (p = 0.701). After PCT levels had been determined, only 21.5% in the PCT-guided group received antibiotics (41.6% reduction). These numbers include 36 patients whose PCT results were over-ruled by clinicians.
Despite the significant difference in antibiotic prescriptions between the two groups, patients did not show any difference in the number of days they were affected by their disease (mean 9.04 days for the PCT-guided group versus 9.00 for the control group, difference 0.04, 95% confidence interval -0.73 – 0.81). There was no significant difference in the outcome between the PCT group that proceeded as advised, the PCT group for which doctors overruled the lab result, and the control group (9.008 versus 9.250 versus 9.000 days, p = 0.9605).
"There is huge potential for further reduction of antibiotic treatment," comments Professor Welte. "A simple PCT-guided strategy of decisions on antibiotic treatment including the option of clinical over-ruling not only reduces the antibiotic treatment rate by 41.6% but is just as safe for patients."
The strength of the PCT-guided strategy is its ability to predict which patients are in need of antibiotics (and which can safely be treated without).
"An important issue is to allow for clinical over-ruling when applying PCT-guided strategies. Although over-ruling was observed in only a minority of patients (13% in our study), doctors would not feel comfortable without this option when caring for their patients."
"We conclude that a PCT-guided strategy applied in primary care in unselected patients presenting with symptoms of acute respiratory infection reduces antibiotic use by 41.6% without compromising patient outcome. The treatment algorithm and measurement procedure are simple enough to be applied even in routine settings."
Prof. Welte has received research grants and fees for lectures from BRAHMS AG, the manufacturer of the lab test.
Contact: (For journalists‘ personal use only, not for publication)
Prof. Dr. Tobias Welte
Title of the original article: "A simple procalcitonin-guided strategy results in safe reductions of antibiotic use in patients with symptoms of acute respiratory tract infections in primary care."