Abstract
Objective
To estimate prevalence and identify factors associated with carbapenem-resistant Enterobacterales (CRE) enteric colonization in companion animals admitted to an ICU.
Methods
The study population included canine and feline patients admitted to The Ohio State University Veterinary Medical Center ICU between January 2024 and June 2025. In total, 5,552 rectal swabs were collected from 3,834 patients during routine screening. A retrospective case-control study included all CRE-positive patients (n = 61) and randomly selected CRE-negative controls (137). Cases were defined as ICU patients with at least 1 positive CRE fecal culture during hospitalization, whereas controls had no positive CRE fecal cultures during their hospitalization.
Results
Prevalence of CRE colonization was 1.59% (61 of 3,834 patients; 95% CI, 1.24% to 2.04%). Escherichia coli carrying blaNDM was the most frequently identified isolate, accounting for 78.7% (48 of 61 patients; 95% CI, 66.9% to 87.1%). Predictors of CRE colonization included increased comorbidity burden (unit OR, 1.96; 95% CI, 1.43 to 2.75), intact reproductive status (OR, 4.39; CI, 1.47 to 11.03), longer hospitalization (unit OR, 1.31; CI, 1.14 to 1.53), recent surgery (OR, 2.72; CI, 1.29 to 5.87), and antimicrobial use within the previous 3 months (OR, 2.71; CI, 1.23 to 6.07).
Conclusions
These predictors suggest targets for infection prevention and control measures to protect patients and staff. The association between recent antimicrobial exposure and CRE colonization reinforces the importance of antimicrobial stewardship in veterinary medicine.
Clinical Relevance
Although uncommon, CRE-colonized patients can serve as reservoirs for transmission and are at risk of subsequent infection.
Keywords: carbapenem-resistant Enterobacterales; CRE; veterinary intensive care; surveillance; enteric colonization
Introduction
β-Lactam antibiotics are among the most frequently prescribed drug classes, used across a wide range of clinical indications. Based on structural differences, they are classified into penicillins, cephalosporins, carbapenems, and monobactams, along with β-lactamase inhibitors that protect these agents from enzymatic degradation.1
Among the β-lactams, carbapenems have the broadest spectrum of activity and are the most potent against gram-positive and gram-negative bacteria. As a result, carbapenems are often reserved for the treatment of highly resistant and/or life-threatening invasive infections in humans and animals, yet bacterial acquired resistance to carbapenems has emerged as an important antimicrobial resistance threat. Of primary concern are the carbapenem-resistant Enterobacterales (CRE) harboring mobile genetic elements that encode for production of carbapenemase that can inactivate all β-lactam antimicrobials.2 Carbapenem-resistant Enterobacterales also frequently acquire resistance to other classes of antimicrobial drugs, making them extremely difficult to treat.3
Carbapenem-resistant Enterobacterales pose a significant threat in human clinical settings, particularly among high-risk patient populations such as those housed in ICUs. They produce opportunistic healthcare-associated infections, including pneumonia, bloodstream infections, and urinary tract infections.4 Infections that are caused by CRE in ICU patients have been linked to high mortality rates.5 In 2011, the NIH Clinical Center in Bethesda, Maryland, experienced an outbreak of CRE resulting from a carbapenem-resistant Klebsiella pneumoniae. Despite the use of aggressive infection control measures, CRE ultimately colonized or infected 18 patients, resulting in 11 deaths.6 The epidemiologic investigation indicated that patients who were asymptomatically colonized, together with environmental reservoirs in the facility, contributed to nosocomial transmission on shared medical equipment.6
Carbapenem-resistant Enterobacterales present a similar risk to patients in veterinary hospitals. In companion animal ICUs of large veterinary referral centers, the transmission of CRE occurs mainly because of the high density of susceptible patients, invasive interventions, and patients receiving antimicrobial treatments including the use of last-resort antimicrobials.7,8 In 2020, a retrospective review9 of a large university veterinary hospital’s records identified 6 animals with carbapenem-resistant Escherichia coli isolated from clinical infections. All the animals were housed in the ICU for more than 24 hours, with each overlapping in time with more than 1 other affected animal. All samples were collected from respiratory specimens, except for 2 urine isolates from a single dog.
Companion animals may serve as potential reservoirs for antimicrobial-resistant bacteria that can colonize or infect humans. In addition, companion animals can acquire antimicrobial-resistant bacteria via multiple routes, including animal or human contact, raw pet food products, and environmental exposure during outdoor activities.10,11 Until recently, animals were thought to play a minor role in the spread of CRE.12 However, reports of sporadic infections in dogs caused by CRE in Germany,13 Spain,14,15 and the US9,16–20 suggest that companion animals might be an overlooked reservoir of CRE. However, data on CRE fecal colonization in companion animals, particularly regarding prevalence and risk factors in ICU settings, remain limited. Understanding the epidemiology of CRE colonization in veterinary ICUs is essential for guiding infection prevention and control and antimicrobial stewardship strategies, as colonized patients may serve as reservoirs for disease transmission.
The purpose of this study was to identify predictors of CRE fecal colonization among canine and feline patients admitted to the ICU at The Ohio State University (OSU) Veterinary Medical Center (VMC). The process of identifying colonized patients and characterizing admission prevalence provides important context for interpreting identified predictors and helps inform infection prevention and control efforts by supporting early detection, reducing nosocomial transmission risk, and guiding rapid response strategies to prevent potential outbreaks within the ICU.
Based on previous literature and human studies, we hypothesized that both host-related and clinical factors, including recent antimicrobial exposure, increased comorbidity burden, prolonged hospitalization, recent surgical procedures, raw diet consumption, and other healthcare- or contact-associated exposures (eg, boarding or immunosuppressive therapies), were associated with increased odds of CRE colonization.
Materials and Methods
Setting and sample population
This retrospective case-control study used data from canine and feline patients admitted to the ICU at the OSU VMC, a tertiary referral hospital, between January 2024 and June 2025. The ICU can accommodate approximately 40 patients at full capacity, with a typical daily census of 20 to 25 patients. As part of routine medical examinations, fecal swabs for CRE screening were collected from all ICU patients upon admission and every 48 hours thereafter during hospitalization. Cases included all patients with enteric CRE colonization identified by fecal surveillance culture, defined as at least 1 CRE-positive culture detected at any time during their ICU stay. Controls were randomly selected from patients that remained CRE-negative on all fecal surveillance cultures collected throughout hospitalization. All eligible CRE-negative patients were assigned a unique numerical identifier. A random number generator (https://www.calculator.net/random-number-generator.html) was used to randomly select the control patients included in the study. Patients with a documented CRE-positive status were assigned a permanent label alert in the electronic medical record, prompting fecal screening at every future visit to the VMC.
Each patient’s fecal swab was inoculated into MacConkey broth modified with meropenem (0.5 µg/mL) and zinc (70 µg/mL) for enrichment. Each tube was incubated during 18 to 24 hours at 37 °C. After incubation, the MacConkey broth was inoculated onto selective MacConkey agar containing 0.5 µg/mL of meropenem and 70 µg/mL of zinc sulfate and streaked for isolation. Colonies that were observed on the selective agar were subcultured onto Mueller-Hinton agar supplemented with meropenem (0.5 µg/mL) and zinc (70 µg/mL). Isolates were tested for carbapenemase production (Carba NP assay),21 screened for CRE genotype with a rapid and visual immunochromatographic assay (NG-Test Carba-5; Hardy Diagnostics), and identified with matrix-assisted laser desorption ionization–time of flight following the manufacturer’s protocol (Bruker Scientific). Antimicrobial susceptibility tests were performed via microbroth dilution to determine the minimum inhibitory concentrations of a panel of antimicrobials included in a commercial plate panel (Sensititre Companion Animal Gram Negative COMPGN1F Vet AST Plate; Thermo Fisher Scientific). Plate reading was performed with a commercial system (Biomic; Giles Scientific), and minimum inhibitory concentration interpretation was performed following Clinical and Laboratory Standards Institute recommendations.22 Because meropenem was not included in the commercial plate panel, additional testing was performed on isolates categorized as susceptible or intermediate to imipenem in the commercial plate panel.
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