Key Point:

• A new rapid serum assay for procalcitonin can indicate the likelihood of a bacterial infection and serve as a guide for whether antibiotic treatment is appropriate.

BASEL, SWITZERLAND—Lower respiratory tract infections are responsible for up to 75% of all antibiotic prescriptions—even though viruses are often the cause of illness. Thus, any method that could enable physicians to better distinguish between the two types of causative organisms could have a dramatic impact on antimicrobial resistance pressures.

Circulating serum calcitonin precursors, such as procalcitonin, are elevated in bacterial infections but remain low in viral infections. Swiss researchers recently studied a new rapid assay for procalcitonin and found that using the assay to guide treatment decisions significantly reduced antibiotic administration and lowered costs—with no adverse effects on outcomes.[1]

PUTTING THE ASSAY TO THE TEST

The study population included 243 patients who presented to the emergency department with cough, dyspnea, or both. When a lower respiratory tract infection was suspected as the cause of the symptoms, the patients were randomly assigned to receive either standard antimicrobial therapy or procalcitonin-guided treatment. The assay requires 20 to 50 µL of plasma or serum; its results, which are generally available within one hour, are interpreted as described in the box below.

Selection of other diagnostic procedures, decision to treat, and choice of therapeutic regimen were left up to the patients’ physicians. In both groups, those who were not initially treated with antibiotics could be reevaluated six to 24 hours after admission. Patients were followed for 10 to 14 days after admission. In addition, patients with COPD had a telephone follow up after six months. The primary end point was use of antibiotics.

There were 119 patients (mean age, 65.3) in the standard therapy group and 124 (mean age, 62.8) in the procalcitonin group. The two groups had similar baseline characteristics (including comorbidities), and they underwent similar types of additional testing. Final diagnoses were also comparable in the two groups; slightly more than one third of each were found to have community-acquired pneumonia, about one quarter had acute exacerbations of COPD, and another quarter had acute bronchitis.

Bacterial cultures were grown from sputum and/or bronchoalveolar lavage fluid in 51 patients and from blood in 16; the organisms identified most often in the cultures were Streptococcus pneumoniae, Haemophilus influenzae, enterobacteria, and Pseudomonas species. The highest number of positive sputum cultures was in patients having acute exacerbations of COPD. However, the rates of positive bacterial cultures were similar in the procalcitonin and standard therapy groups.

Serology detected acute viral infections in 138 of 175 patients tested and multiple viral infections in 46 patients. The most common viruses found were parainfluenza virus types 1 and 3, influenza B, adenovirus, and respiratory syncytial virus. Again, the rate of positive serologic results was similar in the two groups.

Outcome at 13 days was similar in both groups. There were no deaths attributable to inappropriate withholding of antibiotics. However, a marked difference in antibiotic use was seen: 83% of the patients in the standard therapy group received prescriptions for those drugs, but only 44% of those in the procalcitonin group were given them.

Some of the most intriguing results from this study came from subgroup analyses of the patients whose final diagnosis was lower respiratory tract infection or acute exacerbation of COPD—the two groups who should benefit the most from appropriate antibiotic administration. In these two groups, 13-day outcomes were similar, regardless of whether the patients were given procalcitonin-guided treatment or standard therapy. However, the proportion of patients with lower respiratory tract infections who received antibiotics was 47% lower in the procalcitonin group than in the standard treatment group. In patients with acute COPD exacerbations, procalcitonin-guided treatment reduced antibiotic use by 56%. Consequently, among those in the procalcitonin group, the mean per-person antimicrobial costs were reduced by 52% in patients with lower respiratory tract infections and by 36% in those with acute COPD exacerbations.

In the standard therapy group, the patients’ odds of being treated with antibiotics increased by 6.5% for each additional year of age. There was no such age-related increase in the procalcitonin group.

REDUCING ANTIBIOTIC USE

Beat Müller, MD, one of the study’s authors and an Associate Professor of Medicine at University Hospitals in Basel, said that the procalcitonin assay can be used in an outpatient setting as well as in the hospital. In an outpatient setting, the physician would prescribe antibiotics but advise the patient to wait to fill the prescription until the assay results were available later in the day.

The inappropriate use of antibiotics varies among countries, said Dr. Müller; in the United States and France, for example, antibiotics are prescribed far more often than they are in the United Kingdom, Germany, and Switzerland. When asked whether antibiotics were overused because patients expect them or ask for them, Dr. Müller answered that “both doctors and patients are ‘guilty.’”

There are many conditions that could improve with procalcitonin-guided therapy that are currently under investigation, said Dr. Müller. Among them are chronic bronchitis, community-acquired pneumonia, ventilator-associated pneumonia, urinary tract infections, diverticulitis, fever of unknown origin, and meningitis.

—Gale Jurasek