New breath test could quickly diagnose bacterial infections

Infectious diseases are a major cause of death worldwide, and diagnosing bacterial infections remains a challenge in medicine. And doing so reliably is more important than ever, given the increasing frequency of antibiotic resistance. Now, research published in ACS Central Science could help healthcare professionals non-invasively diagnose bacterial infections, using breath-based tests. Initial experiments demonstrated the approach in animals with pneumonia and infections in the bloodstream, muscles and bones. 

In designing this study, we were motivated by a developing trend in clinical practice, whereby patients and providers want answers right away that will inform treatment decisions. If a patient visits the Emergency Room or Acute Care clinic, we hope that he or she can be diagnosed with an acute bacterial infection as efficiently as possible." 

David Wilson, corresponding author of the study

Doctors currently rely on blood tests, imaging, cultures and molecular diagnostics to identify the cause of infections, but these tools are limited because they are slow, non-specific or expensive. The start to a potential solution could be the long-used breath test for Helicobacter pylori, a bacterium that causes a common stomach infection. The original test works when a person drinks a liquid containing traceable substances metabolized by H. pylori. Then the person exhales into a device that measures labeled carbon dioxide in their breath, indicating the infection is present. Inspired by this test, Wilson, Kiel Neumann, Marina López-Álvarez and colleagues set out to expand the technology's capabilities to detect a broader range of bacterial infections. 

For their prototype, the team tested sugar and sugar alcohols tagged with carbon-13, a traceable form of carbon that bacteria metabolize but human cells largely ignore. In lab experiments, the researchers identified several of these compounds that bacteria convert into carbon-13-labeled carbon dioxide. Then they analyzed the labeled gas using a simple technique called nondispersive infrared spectroscopy. 

When mice with infections such as pneumonia and bone, muscle, or blood infections received intravenous injections of these tagged compounds, the animals' breath quickly showed elevated levels of the labeled carbon dioxide. Although the breath testing protocol was not optimized in this study, the researchers say they typically saw elevated carbon-13-labeled breath signals in infected animals within the first 10 minutes of metabolite administration and breath sampling. In contrast, the breath of healthy mice showed little to no carbon-13. 

In one infection model for E. coli, the amount of labeled carbon dioxide in the breath decreased during antibiotic treatment as bacterial levels went down, suggesting the method could also be used to monitor how well treatments are working. 

Because breath-test instruments are portable and breath signals appear within minutes after the traceable carbon-13 is administered, the test could potentially deliver results faster than current methods. In addition, the sugar and sugar alcohols used are considered safe for humans, and the researchers say this approach could eventually become a tool for diagnosing bacterial infections. 

The authors acknowledge funding from the National Institutes of Health and the Cystic Fibrosis Foundation. 

The authors have filed a U.S. patent related to this work.