A new study from the Centers for Disease Control and Prevention (CDC) found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be healthcare-associated infections (HCA-CRE).
Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other healthcare facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community-acquired.
CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate — up to 50% in some studies.
Overall, 30% of CREs carry a carbapenemase — an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.
Sandra Bulens, MPH
But in this study, published in the American Journal of Infection Control , of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in CDC’s Division of Healthcare Quality Promotion, told Medscape Medical News, “The findings highlight the potential for CP-CRE to move from healthcare settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”
CDC researchers analyzed data from eight US metropolitan areas between 2012 and 2015 as part of CDC’s Emerging Infections Program (EIP) healthcare-associated infections — community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.
The incidence of CRE cases per 100,000 population was 2.96 (95% CI, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51, 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).
Lance Price, PhD
Asked for independent comment, Lance Price, PhD, of the George Washington University Milken Institute School of Public Health and the Founding Director of GW’s Antibiotic Resistance Action Center, told Medscape Medical News, “What’s striking about these data is that, ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women…At some point, we have to frame drug resistance as a women’s health issue.”
Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”
This is an increasingly serious problem for women, Price says, because “With a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection…If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics…The gateway to the blood is the UTI.”
Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Bulens, however, said that “[Although] 10% of CRE were in persons without healthcare risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”
This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, US deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.
But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii healthcare-associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.
Bulens and Price report no relevant financial relationships.
American Journal of Infection Control. Published online July 27, 2022. Full text
Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. You can find her at drjudystone.com or on Twitter @judystone.
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