A new study by federal and state health researchers indicates invasive Escherichia coli infections are a growing problem in the United States and becoming harder to treat.
The study, by scientists with the Centers for Disease Control and Prevention (CDC) and state and local public health departments, published this week in JAMA Network Open, found an estimated annual incidence rate of more than 74 extraintestinal invasive E coli infections per 100,000 population, with urinary tract infections (UTIs) accounting for more than half of the associated infection types identified by blood culture.
Incidence was more than seven times higher in patients age 60 and older than in younger patients and higher in women than men among younger age-groups.
The study, which was based on active laboratory- and population-based surveillance data from nine labs belonging to the CDC’s Emerging Infections Program (EIP), also found high rates of resistance to antibiotics typically used to treat invasive E coli infections.
The study authors say the findings highlight the “significant burden” of the pathogen in the United States, its role in causing illness and hospitalizations, and the challenges it poses for treatment and infection prevention.
A burdensome infection
When most people hear about E coli infections, they likely think of food poisoning. Reports of E coli outbreaks linked to food are common. While most foodborne E coli infections are mild, some can be severe.
But E coli—the most common gram-negative bacterial pathogen in people—can move beyond the stomach and intestine, causing several other types of infection, according to Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security who wasn’t involved in the study.
“E. coli infections are very burdensome,” Adalja told CIDRAP News. “They are responsible for a significant amount of urinary tract infections, kidney infections, and bloodstream infections.”
Invasive E coli is also a leading cause of sepsis, which occurs when an infection causes a severe immune system reaction that can lead to tissue damage, organ failure, and death. The CDC estimates sepsis affects 1.7 million Americans a year and is the leading cause of death in hospitalized patients.
These are the type of E coli infections that Heather Grome, MD, of the CDC’s Division of Healthcare Quality Promotion, and colleagues were investigating. Despite their clinical importance, they note, no routine US public health surveillance has been conducted for invasive E coli infections.
“Further characterizing the burden of invasive E coli infections in US populations has important implications for informing prevention strategies to improve sepsis detection and management and better protect the health of patients,” they wrote.
Using case data from collected labs in the 9 EIP sites (California, Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) from June through August 2023, the team identified 1,345 incident invasive E coli infections from 1,334 unique case-patients (median age, 68 years; 57.1% female). More than two-thirds (68.3%) of the infections occurred in adults over age 60, and 88.8% were in patients with underlying medical conditions. Ninety-five percent of case patients were hospitalized within 30 days, with 22% requiring intensive care unit admission; 106 patients (7.9%) died.
The 3-month crude incidence rate was 18.7 infections per 100,000 population, and the estimated annual crude incidence rate was 74.1/100,000. Incidence rates were highest for women (83.4/100,000).
“This is one of the first large population-based studies in the United States for this pathogen, and we identified a higher estimated incidence rate in U.S. communities than expected,” Gromes said in an email, adding that similar incidence rates have been found in other countries. By comparison, the annual US incidence rate for two other severe invasive infections that public health officials monitor—methicillin-resistant Staphylococcus aureus and group A streptococcus—are substantially lower.
Concerning rates of antibiotic resistance
Adding to the concern is the level of antibiotic resistance they found in their analysis of the E coli isolates. Substantial resistance was reported for trimethoprim-sulfamethoxazole (28.8%), levofloxacin (26.9%), and ciprofloxacin (25.9%)—three antibiotics that are commonly prescribed for UTIs. More than 15% of isolates were resistant to ceftriaxone, a first-line treatment for sepsis.
In addition, 14% of the infections were caused by E coli carrying extended-spectrum beta-lactam (ESBL) enzymes, which can confer resistance to multiple antibiotic classes and be shared with other types of bacteria. The authors called this finding “alarming” and said it may give pause to clinicians who have to make antibiotic treatment decisions before they’ve received antibiotic susceptibility test results.
This is one of the first large population-based studies in the United States for this pathogen, and we identified a higher estimated incidence rate in U.S. communities than expected.
“The high percentage of antimicrobial-resistant E. coli we identified raises concerns, especially the percentage of E. coli resistant to extended-spectrum cephalosporins—some of the most common antibiotics given to hospitalized patients,” Gromes said. “This finding may have implications for clinicians trying to make critical treatment decisions for patients with life-threatening infections, such as urinary sepsis, frequently caused by E. coli.”
Adalja noted that, over time, the rate of invasive E coli infections with significant resistance to fluoroquinolones (such as ciprofloxacin and levofloxacin), trimethoprim-sulfamethoxazole, and beta-lactam antibiotics (via ESBLs) has increased significantly.
“Having a gauge on their burden and antimicrobial [resistance] helps to risk-stratify the threat,” he said.
Identifying high-risk patients
The study also found that of the 1,223 cases identified from a blood culture, 61% were associated with a UTI. While only 8.8% of infections were classified as hospital-onset, review of health care exposure found nearly half had a health care exposure in the previous year. Roughly 41% were community-onset infections, meaning they had no prior health care exposure.
Alex Sundermann, DrPH, an assistant professor of epidemiology at the University of Pittsburgh who wasn’t involved in the research, said the study’s assessment of prior health care exposure sheds some light on who’s at risk for these infections.
“It was striking that only 8.8% of cases were hospital-onset, while 47% were healthcare associated/community-onset and 41% were truly community-onset,” Sundermann said in an email. “This distribution highlights the need for multi-level public health interventions that better target patients at high risk after recent healthcare exposure—both to prevent readmissions from ESBL E coli sepsis and to better understand where true community-only onset cases are rising.”
Sundermann added that the study provides a great example of how an established sentinel surveillance program like EIP “is an incredibly valuable tool for understanding the true burden of antimicrobial resistance in the US.” He’s hoping this type of analysis can be repeated in the future.
“Having true cross-sectional studies over time would give us a much better understanding of the direction we’re heading in,” he said.
