Escherichia coli (E. coli), shown in a colorized scanning electron micrograph, are the most common bacterial cause of recurrent urinary tract infections and often develop antimicrobial resistance. (image courtesy of NIAID)
Ritu Banerjee, MD, PhD

Researchers at Vanderbilt Health continue efforts to discover how the use of novel technologies can assist in the detection and management of antimicrobial-resistant infections.  

A recent study, published in The Journal of the American Medical Association (JAMA), highlights the results from a nearly two-year multinational trial comparing whether rapid antimicrobial susceptibility testing (AST) for bloodstream infections led to improved clinical outcomes versus standard testing.

It did not.  

But the results suggest there are benefits of using rapid AST for patients and health systems, according to the paper’s first author, Ritu Banerjee, MD, PhD, professor of Pediatrics at Monroe Carell Jr. Children’s Hospital at Vanderbilt and executive medical director of the Antimicrobial Stewardship Program at Vanderbilt Health.  

“Although we did not find differences in clinical outcomes like mortality, we did find that use of the rapid test led to faster antibiotic treatment changes targeting the resistant pathogens,” said Banerjee, who holds the Mark R. Denison, MD Directorship in Pediatrics. “We also saw trends towards shorter length of stay and more successful discharge at 30 days in the subgroups of patients with highly antibiotic-resistant infections. This provides proof of concept that use of rapid tests that can quickly identify resistance, and when implemented together with antibiotic stewardship team review, can improve timely targeted treatment for patients with sepsis.”  

The study enrolled patients from international sites including low-resource areas that have a high prevalence of antibiotic-resistant pathogens.  

According to the study, 899 patients with positive blood culture results for gram-negative bacteria (GNB) located in seven hospitals in Greece, India, Israel and Spain were randomized to receive either the standard AST or the rapid AST plus standard testing. A total of 850 patients were included in the analysis.  

GNB bloodstream infections are a major cause of illness and death worldwide, especially where antimicrobial resistance is more common.  

The rapid method used novel technology to test blood directly from positive cultures, while the standard method used conventional testing on subcultured bacteria. Standard testing can take three days or longer, said Banerjee. Rapid testing can shorten that time to six to eight hours.  

There is a caveat — while faster and more sensitive, rapid testing is more expensive than conventional/standard methods.  

“We performed the study because before implementing these new tests for routine clinical use, it’s important to evaluate whether they actually impact clinical decision-making and outcomes for patients,” said Banerjee.  

“Better diagnostics are only one part of the complex solution to address antibiotic resistance. Diagnostics need to be thoughtfully implemented, with coordination between the microbiology laboratory, antibiotic stewardship teams and clinicians. Diagnostics also need to be paired with effective therapeutics.  

“Not all sites participating in the trial had ready access to first-line antibiotics, highlighting the need for equitable access to new antibiotics when they are developed,” said Banerjee.  

In future efforts, researchers plan to analyze the cost-effectiveness of using rapid testing; evaluate outcomes using different implementation strategies for rapid diagnostics; and evaluate pairing diagnostics with effective therapeutics for sepsis or other types of infections.  

The clinical trial is registered as NCTO6174649. The research was supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (grant UM1AI104681).