Columbus, OH - January 2016
Three antimicrobial peptides essential to the innate immune system may also serve to signal acute urinary tract infection (UTI), researchers from Nationwide Children’s Hospital and The Ohio State University’s College of Medicine have found.
In a preliminary study of adult emergency department patients at The Ohio State University Wexner Medical Center, the abundances of the peptides rose significantly among those with infection, including — perhaps most importantly — hard-to-diagnose elderly patients.
The research builds on work done at Nationwide Children's showing that the peptides, referred to as AMPs, are in urine and kill bacteria. The new study is published in the journal Academic Emergency Medicine.
Its authors are pursuing more accurate rapid diagnostic tests for UTI, suffered by hundreds of thousands of children and adults annually.
"The current tests are inaccurate and inadequate," says Jeffrey Caterino, MD, associate professor of Emergency Medicine and Internal Medicine and vice chair of research for the Department of Emergency Medicine at The OSU College of Medicine.
"This preliminary work indicates some antimicrobial peptides are good markers for diagnosing infection," Dr. Caterino, who led the research, says.
Andrew Schwaderer, MD, research director in the Section of Nephrology at Nationwide Children's and principal investigator at the Center for Clinical and Translational Research in The Research Institute at the hospital, tested the samples from the 40 adult patients. He was not surprised to see higher levels of AMPs in patients with infection. "These are natural antibiotics," he said.
The three that showed significantly higher levels associated with UTI were human neutrophil peptide 1-3, human alpha-defensin 5 and human beta defensin 2.
The increase in their abundances held true among young adult and middle-age patients and a subgroup of older adults, who have proven especially hard to diagnose accurately.
"Older adults often have infection without classic symptoms," Dr. Caterino says. "And older adults may be colonized with bacteria, so even though we find bacteria in the urine, it doesn't truly indicate UTI."
Like adults, children are under- and over-diagnosed. The errors can leave them suffering or cause them to take antibiotics they don't need, adding to the growing problem of bacterial resistance, Dr. Schwaderer says. The more accurate of the two tests available is a culture that can take one to three days.
"We're looking for diagnostics that more accurately and rapidly treat children with UTI," he says.
The researchers are now seeking funding from the National Institutes of Health for a five-year study looking at 500 emergency room patients at Wexner Medical Center, to see if they can confirm the preliminary findings and find the cutoff points of infection and non-infection. If the study is funded, they expect to begin in the spring.
Because the body's immune system changes with age, the results of the adult study may not apply to children. Dr. Schwaderer recently completed a preliminary study of children and AMPs. The findings are on track to be published early next year.
"If AMPs prove to be good biomarkers in adults or children, we hope to develop what's called a lateral flow assay," he says. "The test would be similar to current fast-acting pregnancy tests, providing answers within a matter of minutes."
Caterino JM, Hains DS, Camargo CA, Quraishi SA, Saxena V, Schwaderer AL. A prospective, observational pilot study of the use of urinary antimicrobial peptides in diagnosing emergency department patients with positive urine cultures. Academic Emergency Medicine. 2015 Oct;22(10):1226-30.