WHO has included CRE in its Indian list of antibiotic resistant ‘priority pathogens’ category which indicates that these are pathogens of serious concern.¹⁵

The present study was conducted to determine the prevalence and risk factors associated with faecal carriage of CRE in hospitalized patients in a tertiary care teaching institute through active surveillance in various wards and ICU’s. Few studies from India have investigated CRE prevalence in faecal samples.^10,16

The prevalence of CRE colonization among the enrolled patients was found to be 13.3%, indicating a significant burden of carbapenem resistance. This finding is consistent with previous studies that have reported high rates of CRE carriage in healthcare facilities i.e. 18.1% by Mohan et al. in 2012-2013, 51.85% by Saseedharan et al. in 2015 in ICU, 19.9% by Sharma et al. in 2019-2020.^1,10,16 Studies from some western countries show a much lesser prevalence as compared to the present study.^3,17 These low rates could be due to restricted availability of antibiotics, strict hospital infection protocols and antibiotic stewardship programmes. A high prevalence in this study may be due to greater exposure to antibiotics previously (carbapenems, cephalosporins, aminoglycosides) as this hospital is a tertiary care centre. CRE can be transmitted easily from person to person through the hands of health care workers (HCW’s) or hospital equipment and patient devices.⁶ CRE can also be acquired endogenously from the gut because of antibiotic selection pressure.⁶ Knowledge of CRE carriage is essential as these asymptomatic colonizers can act as potential reservoirs for transmission of infections in the hospital environment.^1,6,18 Currently, there are no recommendations for CRE faecal carriage in India. Countries like Korea have declared CRE as a notifiable disease, especially in high-risk areas as per guidelines from WHO.^1,11

This study revealed that patients in the higher age group, i.e. above 60 years and males, had the highest proportion of CRE colonization. These observations are in line with previous studies that have identified higher age and male gender as risk factors for colonization.^{6,12,14,19,20} The higher prevalence of CRE in older individuals may be attributed to a higher frequency of hospitalizations, co-morbidities, antibiotic usage, and increased exposure to healthcare-associated risk factors.^20,21

Species-wise distribution demonstrated that E. coli was the most common CRE species identified, followed by Klebsiella species. These findings are consistent with global trends where E. coli and Klebsiella species are the predominant CRE isolates.^{1,16,19,20,22} The unique emergence of E. coli as the predominant CRE strain in this specific study diverges from some other studies that report higher percentages of Klebsiella, i.e. 87%, 42.2%, 39.3% and 70% as compared to E. coli, i.e. 7.9%, 24.3%, 21.97%, 11.7%.^{1,12,16,20,22} This might indicate a local increase in resistance among E. coli strains.

Though E. coli was the predominant CRE in the present study, a higher proportion of K. pneumoniae were found to be carbapenemase producers (69%) which is similar to other studies.²³ It is believed that the production of thick capsules and extensive ability to produce biofilms on indwelling foreign bodies like prosthetics give Klebsiella a survival advantage and it also has the capability of acquiring multiple multidrug-resistance plasmids.^24,25

With regards to distribution of CRE in different clinical settings, higher proportion was observed in ICU patients, particularly in the surgical departments which was observed in other studies too.^1,16,20 Surgical patients have increased chances of colonization due to invasive procedures, catheter and other invasive devices in situ and longer hospital stay. ICU patients often have longer stay in the ward, even before being admitted to the ICU, more chances of mechanical ventilation and exposure to antibiotics, thus increasing their exposure to healthcare settings and potentially to resistant bacteria. There are studies that have demonstrated that CRE rates are higher in medical ICU’s as compared to surgical ICU in contrast to the present study.¹⁰ Medical ICU patients have been found to be older, have more carbapenem usage, longer hospital stay and more cases are bedridden ones.¹⁰

A significant proportion of isolates tested positive for carbapenemases (54.3%) of which 19.6% were serine carbapenemase producers. This may be useful as ceftazidime-avibactam combination can be used to treat cases producing serine carbapenemases.¹⁰ Other studies have also demonstrated high proportion of carbapenemase producers.^1,26 Epidemiological surveillance from India has confirmed NDM-1 to be widely disseminated in healthcare settings as well as in environment and is the predominant carbapenem-resistant mechanism in India.²⁷

CRE strains exhibited decreased susceptibility to all tested antimicrobial classes compared to carbapenem-sensitive Enterobacterales (CSE) strains. CRE strains often possess various mechanisms such as efflux pumps, porin mutations, and acquisition of resistance genes on mobile genetic elements, contributing to resistance against multiple antibiotic classes.²⁸ Probable risk factors for faecal carriage of CRE by univariate logistic regression analysis demonstrated that history of surgical intervention (p = 0.0012), presence of urinary catheter (p = 0.0018) and central venous line (p = 0.0308), previous exposure to antibiotics like carbapenems (p = 0.0239), cephalosporins (p = 0) and aminoglycosides (p = 0.0111), H/o diabetes mellitus (p = 0.0004), renal disease (p = 0.0057), malignancy (p = 0.0139), corticosteroid use (p = 0.0194) were associated with increased risk of CRE colonization. Previous studies reported similar risk factors for acquiring faecal colonization with CRE infection.^1,2,26,29 Multivariate analysis done found four independent risk factors for colonization-history of surgical intervention, previous exposure to cephalosporins, previous exposure to aminoglycosides and diabetes mellitus.

On calculating the odds ratio, chance of CRE carriage in stool was found to be 7.54 times higher in patients with previous exposure to cephalosporins, 4.88 times higher with previous exposure to aminoglycosides, 4.35 times in diabetic patients and 3.42 times in patients having history of surgical intervention.

This study also identified chronic diseases like diabetes mellitus, malignancy, renal diseases as risk factors. Such patients could have had recurring admission as well as a relatively longer length of stay (mean days 15.4 v/s 5.2) (p = 0.0005) exposing them to greater risk than the general patient population.^1,10,20

This study highlights the need for effective infection control measures, including early detection and isolation of CRE carriers to prevent the spread of these multidrug-resistant bacteria. Targeted infection control measures aimed at the identified risk factors, consistent antimicrobial stewardship initiatives, enhanced hand hygiene practices, and effective surveillance can aid in decreasing the transmission of CRE and stopping its further spread.

Limitations of the study
It is important to acknowledge certain limitations of this study. First, the study was conducted in a single tertiary care teaching hospital, which may limit the generalizability of the findings to other healthcare settings. Second, the study focused only on faecal carriage of CRE and did not assess the clinical impact of CRE colonization or infection. Thirdly, a study with a larger sample size could give better results but due to the ongoing COVID pandemic, patient reporting to the hospital were limited and therefore lesser number of enrolments could be done. Fourthly, all the tests used for detection of the resistance mechanism were phenotypic and were not confirmed by carrying out molecular detection of resistance genes.³⁰ Future studies should explore the clinical outcomes associated with CRE colonization to further understand the implications of these findings.