Editor’s Note: Bacterial drug resistance is a significant challenge in the global public health field. Multidrug-resistant organisms (MDROs), represented by carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and vancomycin-resistant Enterococcus (VRE), exhibit high resistance and rapid transmission. Previous studies have established a close relationship between intestinal CRE colonization and infection, but the relationship between intestinal colonization and infection of other MDROs remains to be clarified. In a recent oral presentation at the 2023 Infectious Diseases Week (IDWeek 2023), a researcher reported a study on the relationship between MDRO intestinal colonization and the risk of bloodstream infection (BSI). Dr. Yonghong Xiao, from the First Affiliated Hospital, Zhejiang University School of Medicine, provides an introduction and commentary on this research.
The First Affiliated Hospital, Zhejiang University School of Medicine
Study Overview
Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection (Abstract No. 2076)
Background
The relationship between rectal colonization with multi-drug resistant organisms (MDROs) and subsequent bloodstream infection (BSI) is still not well understood. This study aimed to investigate the relative risk of MDRO rectal colonizers developing BSI and whether BSI caused by carbapenem-resistant Enterobacteriaceae (CRE) was due to the patient’s own colonizing strains.
Methods
A retrospective study included adult patients admitted to three Greek hospitals (Attikon Hospital, Tzaneio Hospital, AHEPA Hospital) from January 2019 to December 2022, in ICU or other wards, who underwent weekly screening for MDROs colonization upon admission. CRE’s carbapenemase was detected using selective culture media and immunochromatography. Patients with BSI caused by the same colonizing strain were followed up, and relative risk (RR, 95% CI) was estimated after adjusting for ICU length of stay and age. MDROs included CRE, CRAB, CRPA, and VRE. The carbapenemase types of CRE colonizing strains and BSI pathogens were analyzed to determine potential similarities.
Results
Among the 4,427 screened patients, 1,321 (29.8%) were CRE colonizers, 1,255 (28.3%) were CRAB, 252 (5.7%) were CRPA, and 859 (27.9%, out of 3,082 tested patients) were VRE. Among them, 207 (15.7%), 247 (19.7%), 23 (9.1%), and 30 (3.5%) patients subsequently developed CRE, CRAB, CRPA, and VRE-BSI, respectively. After adjusting for ICU length of stay and age, patients with intestinal CRE colonization had a fourfold increased risk of developing CRE-BSI (RR 4.1, 95% CI: 3.2-5.2). The RR (95% CI) for patients with CRAB, CRPA, and VRE colonization developing BSI were 2.3 (1.9-2.8), 8.2 (5.1-13.4), and 2.1 (1.3-3.4), respectively. To assess potential horizontal transmission, 286 pairs of CRE strains from 143 patients were analyzed. Among them, 101 (70.6%) patients’ colonizing strains and BSI pathogens belonged to the same bacterial species and carried the same carbapenemase types.
Conclusion
MDRO intestinal colonization is associated with an increased risk of colonization strains causing BSI. Clinicians should consider this when initiating empirical treatment, and complete genome data is needed to confirm horizontal transmission.
Expert Commentary
Although this study is retrospective, it included over 4,000 patients from three hospitals and examined a variety of bacterial species, making it clinically valuable.
As we know, drug-resistant bacteria are common pathogens in hospital infections, especially in large tertiary hospitals where various drug-resistant bacteria are prevalent. The development of drug-resistant bacteria follows a specific path, including the invasion of patients by drug-resistant bacteria in the hospital environment, gradual development of resistance in sensitive bacteria after antibiotic use, and the selection of small amounts of drug-resistant bacteria during treatment, all of which may lead to the presence or development of drug-resistant bacteria in patients.
The gut is commonly considered the “hub” for various microorganisms and their source. Therefore, based on many previous studies, although infection cases are complex and diverse, the source of pathogenic microorganisms often originates from the gut. This study focused on four common MDROs, namely CRE, CRAB, CRPA, and VRE. The researchers conducted screening for MDRO colonization in patients, which confirmed a significant detection rate. This suggests that the carriage rate of drug-resistant bacteria, especially in the gut, increases in hospitalized patients, and subsequent follow-up data indicates that patients colonized with drug-resistant bacteria have a higher risk of infection. At first glance, it appears that drug-resistant bacteria are transmitted from the gut, a “hub” of microbial activity, to other sites, leading to bloodstream infections, but there may be other transmission routes, such as bidirectional regulation of the “gut-lung axis.”
In summary, while the results and conclusions of this study are not novel, they reaffirm that the source of drug-resistant bacterial infections is often the gut, and screening for gut colonization with drug-resistant bacteria is valuable for diagnosing and treating infected patients and for hospital infection control. This study’s value is mainly reflected in three aspects:
First, infection control for patients with drug-resistant bacterial infections. For high-risk patients with drug-resistant bacterial infections, if screening reveals the presence of drug-resistant bacteria in the gut, clinicians will consider the possibility of drug-resistant bacterial infections when initiating empirical antibiotic treatment, making the treatment more targeted.
Second, eradicating drug-resistant bacteria. When proactive screening reveals colonization with drug-resistant bacteria, various methods can be employed for eradication. Although there is no clear evidence regarding the effectiveness of specific methods, eradication is a valuable approach for preventing drug-resistant bacterial infections. Non-absorbable antibiotics have traditionally been used for eradication, with a focus on aminoglycoside antibiotics. Some recent studies have suggested using oral polymyxin antibiotics for eradication, but their effectiveness requires long-term observation. In recent years, with the emergence of infection microbiome theory, some researchers have proposed using fecal microbiota transplantation for drug-resistant bacteria clearance and eradication, but clear results are still pending. I believe that eradication is a valuable area of research in infection control and warrants further exploration.
Third, patient isolation and protection. When screening reveals MDROs, and even extensively drug-resistant organisms (XDROs) colonization, clinical practices should include appropriate isolation measures. For example, (1) single-room isolation is preferred whenever possible. Considering that many hospitals in China may not meet this isolation standard, bedside isolation is an alternative option. Special equipment and items such as stethoscopes, blood pressure cuffs, thermometers, and infusion stands used for direct patient contact should be dedicated and disinfected promptly. (2) Healthcare workers should wear gloves when performing diagnostic and nursing procedures on patients and, if necessary, wear isolation gowns. After completing diagnostic and nursing procedures, gloves and isolation gowns should be removed promptly, and hand hygiene should be strictly observed. (3) Environmental cleaning and disinfection should be intensified, with increased frequency and appropriate disinfectants used for wiping and disinfection. (4) For patient units after discharge, terminal disinfection should be performed using devices such as hydrogen peroxide disinfection machines. The infection control department should regularly monitor the effectiveness of environmental object cleaning and disinfection.
Of course, this study has some limitations. First, the study did not perform molecular studies to confirm whether the strains isolated from the infection site genuinely originated from the gut. While previous studies support the close relationship between CRE colonization and infection, the researchers could not confirm the transmission of CRE from the gut to the bloodstream due to the lack of whole-genome sequencing data.
Second, the study only analyzed screening and infection occurrence and did not report on patient outcomes. It would be valuable to know if there are differences in empirical antibiotic treatment approaches for patients who underwent gut colonization screening and those who did not. Whether these differences affect patient outcomes is an important consideration, but the researchers did not report on this aspect at the conference. Hopefully, supplementary information will be provided in future reports.
The above points provide insights into the study’s significance and limitations. This study falls under the category of basic research in the field of drug-resistant bacteria, and numerous studies have explored the mechanisms of drug-resistant bacteria transmission related to the gut. Many studies focus on the relationships between gut microbiota, the mucosal immune system of the gut, and the influence of the migration and metabolism of microbiota in different body sites on drug-resistant bacteria transmission. The quantity and quality of related research are both high.
Furthermore, the study of the impact and mechanisms of antibiotics on gut microbiota and intestinal mucosal barrier function is crucial. (1) Antibiotic use may kill some bacteria that can suppress drug-resistant bacteria, affecting bacterial metabolism and increasing drug-resistant bacteria. (2) Gut microbiota are associated with gut barrier function and the mucosal immune system of the gut. When gut function is disrupted, bacteria that promote gut mucosal barrier function are in a state of imbalance. This impairs the biological and chemical barrier function of the gut mucosa, allowing gut bacteria to enter the mucosa, migrate to extraintestinal organs, and lead to infections in other sites, bloodstream infections, and even sepsis.
In conclusion, this study is relatively basic clinical research with value for future in-depth research. Such studies span the fields of infectious diseases, infection control, and drug resistance prevention, and they are relatively common in academic conferences on infectious diseases.
References
Polyxeni Karakosta, et al. Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection. ID Week 2023; abstract 2076.
