Procalcitonin (PCT) levels, a precursor of the hormone calcitonin, have been found to increase during a bacterial infection. It has been extensively evaluated in the management of lower respiratory infections, especially to guide initiation and interruption of antibiotic therapy. In addition to distinguishing between bacterial and viral etiology, PCT values have also been found to be higher in community-acquired pneumonia (CAP) caused by typical, and particularly by S. pneumoniae, than by atypical bacteria like Mycoplasma, Chlamydophila, Legionella, or Coxiella.
Researchers, from Alicante and Elche, Spain, performed a study to examine the role of PCT in guiding the initial selection of the antibiotic regimen for low-risk CAP. They determined that the PCT-guided strategy, using rapid point-of-care testing, safely allowed the selection of empirical narrow-spectrum antibiotics in outpatients with CAP, according to a study that was published in the April 20, 2017 issue of the journal PLOS ONE.
“Distinction between infections caused by typical and atypical respiratory pathogens is difficult and cannot be made solely on clinical grounds,” wrote the study authors led by Mar Masiá, who is in the Infectious Diseases Unit at Hospital General Universitario de Elche at Universidad Miguel Hernández in Alicante, Spain. “The availability of biological predictors of atypical etiology might help avoiding overuse of fluoroquinolones and selecting candidates for monotherapy with macrolides in patients with CAP.”
Study authors performed a single-arm clinical trial that included outpatients with CAP. They had Pneumonia Severity Index risk classes I-II. In addition, antimicrobial selection was based on the results of PCT measured using rapid point-of-care testing.
The study’s exclusion criteria included PSI risk classes III-V; age ≥65 years; comorbidity with diabetes, chronic obstructive pulmonary disease, chronic renal disease, neoplasm, immunosuppression including HIV infection, chronic heart failure, or cirrhosis; a white blood cell count ≥20.0 x 109/L, pleural effusion, bilateral infiltrates, previous failure or allergy to macrolides or quinolones, and need for oxygen therapy.
According to the serum PCT levels, patients were assigned to two treatment strategies. They were assigned to oral azithromycin if their PCT was
Study authors noted that a historical control group of outpatients matched for disease and PSI risk class, and treated according to usual practice in the same facility, was selected for comparison.
“We estimated a sample size of 232 patients for a pre-specified threshold failure rate of 10%, with an 85% power and a two-sided alpha level of 0.05,” the researchers explained. “The planned sample size was increased by 10% to 254 patients to account for losses to follow-up.”
Researchers reported that of 319 assessed patients with PSI risk classes I-II, 253 (79.3%) patients were finally included in the study. Of the 253 patients, 216 (85.4%) were assigned to azithromycin. No patients included in the study were lost to follow-up.
They pointed out that the etiological agent was successfully identified in 22 (59.5%) patients placed on levofloxacin and in 71 (32.9%) patients on azithromycin. Thirty-four (15.7%) patients receiving azithromycin and 21 (56.8%) patients receiving levofloxacin were diagnosed with typical bacterial infection. In 40 (18.5%) patients included in the azithromycin and 3 (8.1%) in the levofloxacin group, respectively, an atypical microorganism was identified.
In addition, it was reported that a diagnosis of pneumococcal infection was established in 26 (12%) patients receiving azithromycin; of them, S. pneumoniae was isolated from the sputum culture in 7 (26.9%) patients. In 2 of these cases, the pneumococcal isolate was resistant to macrolides, with an erythromycin MIC ≥1 μg/ml. These isolates also had intermediate susceptibility to penicillin (MIC of 0.25 and 0.12 μg/ml, respectively). Pneumococcal infection was diagnosed in 21 (56.8%) patients who received levofloxacin. In 6 patients, S. pneumoniae was isolated from sputum or blood cultures; one of them (16.6%), isolated from sputum, was resistant to azithromycin (MIC ≥1 μg/ml).
Procalcitonin levels were
“Our study demonstrates the short-term and long-term safety and efficacy of an intervention guided by PCT levels for the election of the antibiotic regimen in outpatients with CAP,” researchers reported. “When it was implemented to use azithromycin monotherapy in an area of high prevalence of pneumococcal macrolide resistance, a high clinical cure rate was achieved, that was comparable to the rate of responses observed with the standard strategy of the historical control group.”
They also noted that compared with usual care, their approach allowed a narrowing of the antibacterial spectrum and they avoided overuse of fluoroquinolones.
They concluded that their strategy, guided by PCT levels to treat outpatients with CAP using a rapid point-of-care testing, allowed narrowing the antibacterial spectrum in a large percentage of patients.
“The intervention was accompanied by a high rate of clinical response, comparable to that obtained with usual practice, and by no short-term and rare long-term recurrences,” they explained. “Implementation of this strategy might help clinicians to select the most appropriate initial empirical antibiotic regimen, and may be advantageous in terms of costs and ecological impact.”