According to the World Health Organization (WHO), the threat of antibiotic resistance is largely fueled by the misuse and overuse of antibiotics. Part of the WHO’s global action plan includes the development of new tools to help physicians distinguish between bacterial and viral infections to reduce unnecessary antibiotic use in the latter.
Serum procalcitonin (PCT), a precursor to the hormone calcitonin, has been used as a biomarker to assess the severity of bacterial infections since the early 1990s. PCT is suppressed during viral infections but secreted in response to bacterial infections, allowing physicians to differentiate between the two types of infectious agents. Serum PCT levels change quickly in response to infection severity according to the levels of circulating proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α.
While clinicians currently use PCT testing to guide antibiotic treatment in severe sepsis, pneumonia, and lower respiratory tract infections (LRTI), researchers are now investigating whether PCT testing can reduce unnecessary antibiotic use in COVID-19 patients.
Using PCT to combat antibiotic resistance
As rates of antibiotic resistance rise, it is essential to decrease unnecessary antibiotic use without putting patients at risk. Recent evidence suggests that using serum PCT testing to guide antibiotic use can accomplish that goal by safely reducing the number of patients on antibiotics and the duration of antibiotic use, as well as reducing antibiotic-related side effects.
In 2017, the FDA approved serum PCT testing for patients with LRTIs, as well as to guide termination of antibiotics in patients with sepsis. Likewise, in January 2020, the FDA approved another PCT test for the diagnosis of sepsis, which produces results in about 20 minutes.
Conflicting views on PCT
However, there are conflicting views on PCT within the medical community, which are reflected in clinical practice guidelines used by physicians. A recent review examined 17 clinical guidelines on PCT testing from 2009 to 2018 and found that, though the majority recommended PCT testing, especially concerning pneumonia and sepsis, four guidelines had not found enough clinical evidence to make a recommendation and one did not recommend PCT. Despite the differing opinions on PCT, the authors noted that two of the most recent guidelines published in 2018 did recommend PCT testing, speculating that this result may be due to more recent studies favouring its use.
Indeed, in 2019, a group of experts published an improved clinical algorithm for PCT-guided antibiotic use in sepsis and community-acquired pneumonia patients, recommending that physicians use different PCT cutoffs according to the severity of disease and measure PCT every 24-48 hours.
But the 2019 American Thoracic Society and Infectious Diseases Society of America guideline on community-acquired pneumonia does not recommend PCT-guided antibiotic treatment, citing a recent study that could not identify PCT cutoff values that accurately differentiate bacterial from viral infections, though the study did find that higher serum PCT values were strongly associated with bacterial infections.
Further complicating the interpretation of PCT cutoff values, baseline serum PCT levels can vary in different subpopulations, including different age groups or patients with underlying health conditions.
Though many clinical guidelines endorse the use of serum PCT testing to guide antibiotic treatment in LRTIs, PCT testing remains controversial, where some clinical guidelines do not recommend its use due to a lack of strong clinical evidence. Either way, many healthcare professionals continue to prescribe antibiotics to most patients hospitalized with respiratory infections, including those hospitalized with SARS-CoV-2 infection.
Unnecessary antibiotic use in COVID-19
Currently, the vast majority of COVID-19 patients receive antibiotics, as severe forms of the illness can progress to bacterial pneumonia and sepsis, requiring antibiotic treatment. But researchers have found that only about 10 percent of COVID-19 patients actually have bacterial coinfections.
In an effort to reduce unnecessary antibiotic treatment in COVID-19, the co-chairs of the American Thoracic Society and Infectious Diseases Society of America’s 2019 guideline on community-acquired pneumonia endorsed the use of PCT testing as a way to reduce unnecessary antibiotics in COVID-19 patients.
Reducing unnecessary antibiotics could help improve patient outcomes, especially in elderly patients, which make up a large part of COVID-19 patients and are at higher risk of adverse reactions to antibiotics.
Using PCT testing to reduce antibiotic use in COVID-19
To date, several studies have found that elevated PCT is associated with poor COVID-19 patient outcomes. In June 2020, a systematic review and meta-analysis that included data from over 5000 COVID-19 patients found that those with elevated serum PCT levels were almost 4 times more likely to have poor outcomes, while another reported patients with elevated PCT were almost 5 times more likely to develop severe COVID-19. Thus, PCT testing may be able to identify patients with bacterial coinfections who are at risk of developing severe COVID-19 and require antibiotics.
However, hyperinflammation in severely ill patients, known as cytokine storms, may also lead to elevated serum PCT. In addition, many patients susceptible to COVID-19, such as the elderly and those with underlying health conditions, make interpretation of serum PCT values difficult due to varying baseline measures, potentially leading to inaccurate results. So, the challenge is accurately identifying which patients have bacterial coinfections, and which do not.
More research on PCT in COVID-19 is needed
Though some research has shown that PCT testing can help reduce unnecessary antibiotic use and related side effects, improving outcomes in patients with respiratory infections, the debate over whether PCT values can reliably differentiate between bacterial and viral pneumonia persists.
But as international guidelines continue to recommend empiric antibiotics for severe COVID-19,further research on whether PCT testing can identify patients with bacterial coinfections is needed to reduce unnecessary antibiotic use.