Early in 2019, new research from Mercy Health in Fairfield, Ohio showed that patients with indwelling urinary catheters, a history of recurrent urinary tract infections, or recent antimicrobial use are at a higher risk for community-acquired extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) urinary tract infections (UTIs).
The report, published in Open Forum Infectious Diseases by Dheeraj Goyal, MD, MPH, medical director of infection control and antibiotic stewardship at Mercy Health, and colleagues, states that the prevalence of ESBL infections is increasing. Goyal and colleagues conducted a case-control study of 251 adults admitted to an Intermountain Healthcare hospital with a UTI between 2001 and 2016.
According to the analysis, a history of repeated UTIs, neurogenic bladder, urinary catheter presence at admission and exposure to outpatient third-generation cephalosporins or fluoroquinolones within 3 months were associated with a higher risk for ESBL UTIs. When they controlled for severity of illness and comorbid conditions, the researchers found that a history of repeated UTIs (adjusted OR = 6.4; 95% CI, 3.42-12.66), presence of urinary catheter at admission (aOR = 2.36; 95% CI, 1.15-4.98) and prior antibiotic exposure (aOR =7.98; 95% CI, 2.92-28.19) remained associated with a higher risk for ESBL infection.
What does this mean?
While this study is first to report on the rise of community-acquired ESBL UTIs, it is not surprising to see that it is consistent with what has been reported for hospital-acquired ESBL UTIs or the general rise in ESBL bacteria in published surveillance studies. Also noteworthy, is that this study determined the risk factors for community-acquired ESBL UTIs, and they are the same for hospital-acquired ESBL UTIs: a) history of recurrent UTIs, b) history of a urinary catheter in recent past, and c) exposure to antibiotics in recent past. It underscores the factors which lead to the rise in ESBL UTIs, but also implies the blurring line between hospital- and community- acquired antibiotic resistant bacteria.
With the rise in ESBL UTI infection rates, patients have greater probability to not respond to front-line antibiotics. Empiric use of carbapenems for patients with these risk factors may lead to improved patient outcomes and shorter hospital lengths of stay, but it is not without other risks and challenges. Increased use of carbapenems will also drive resistance to this drug class known as the “last resort.” This will be an undesirable outcome and a failure to antibiotic stewardship programs.
The study points out that patients with ESBL and non-ESBL Enterobacteriaceae infections often have similar symptomology, thus making empiric therapy decisions difficult. Patient history may also be absent or not accessible at the time of decision for empiric therapy. With ESBL rates rising at the same time when antibiotic stewardship programs struggle to preserve the last resort carbapenems, use of patient risk factors alone may not be enough to navigate the treacherous waters of antibiotic resistance.
The OpGen difference.
There is a technological solution in development for the critical and escalating antibiotic resistance problem. It combines the power of bacterial genetics and bioinformatic analysis. We are developing products, the Acuitas® AMR Gene Panel and Acuitas Lighthouse® Software, to provide results to guide empiric therapy decisions within 3 hours of sample collection; days faster than traditional culture methods. The Acuitas AMR Gene Panel, currently available for Research Use Only and not for use in diagnostic procedures, detects the presence of pathogen and antibiotic resistance genes directly from a urine specimen. The Acuitas Lighthouse Software, also available for Research Use Only and not for use in diagnostic procedures, predicts antibiotic resistance using algorithms and a knowledgebase which OpGen built by genotyping and phenotyping over 15,000 resistant isolates from around the world.
In an example specific to this study, a urine specimen from a patient having these risk factors or suspected of having these risk factors can be tested using tools such as the ones we are developing. Quickly, and with high accuracy, resistance to penicillins and cephalosporins, as well as resistance to carbapenems, can be predicted. For the first time, clinicians would have precision medicine guidance to help navigate the growing ESBL issue. They will have rapid precision tools directing them when and when not to use “last resort” carbapenems or restricted antibiotics for front-line therapy.
Understanding patient risk factors will remain important but use of a rapid test and knowledgebase to guide empiric therapy with precision will be essential to improve patient outcomes, lower hospital costs, and protect our supply of effective antibiotics in the age of antibiotic resistance.