Omics-based susceptibility analysis

Prioritization of patients for placement in isolation rooms can be significantly enhanced through patient risk assessment and integration of omics technologies that provide a deeper understanding of individual susceptibility and transmission risks. Advancements in omics technologies have revolutionized the field of medical research, offering profound insights into the complex interactions between hosts and pathogens. In the study of colonization and infection, patient omics, including genomics, transcriptomics, proteomics, metabolomics, and microbiomics, can offer a detailed view of biological processes. These insights pave the way for personalized medicine approaches that can improve prevention, diagnosis, and treatment for infectious diseases. ^{Reference Tebani, Afonso, Marret and Bekri17} Developments in these technologies have transformed personalized IPC by allowing the identification of host genetic factors that affect susceptibility to infection and the risk of transmission. By customizing isolation measures according to individual omics profiles, isolation strategies can be more precise and effective. Omics data allow for the identification of host genetic factors that influence susceptibility to infections and individual responses to treatments. This facilitates personalized medicine approaches, where interventions can be tailored based on a person’s genetic predispositions and microbial profiles. ^{Reference Bosnjak, Karpe and Van18,Reference Fishbein, Robinson and Hink19} However, there is a gap in the literature regarding association between patient omics and pathogen acquisition, and further studies are needed to address this issue.

Underlying health conditions and colonization risk

Factors such as increased colonization sites, advanced age, morbidities, previous antibacterial therapy, cancer chemotherapy, previous gastrointestinal surgery, prior healthcare exposure including in long-term facilities and previous detection of MDR pathogens further increase the risk of colonization. ^{Reference Bearman, Harris and Tacconelli20} A hospital-based case-control study identified liver cirrhosis, previous MDR-GNB carriage, digestive surgery, and length of hospital stay within the previous year as independent risk factors for MDR-GNB colonization. However, only liver cirrhosis had a strong association with MDR colonization. ^{Reference Fernández-Martínez, Cárcel-Fernández and De la Fuente-Martos21}

Hu et al. ^{Reference Hu, Zhang and Wei22} demonstrated that continuous carriage extends the shedding of carbapenem-resistant Klebsiella pneumoniae (CRKP) into the environment, leading to persistent contamination. Additionally, a prolonged intensive care unit (ICU) stay (>6 weeks) increases interactions with other patients and HCWs, thereby expanding contamination and facilitating the spread of bacterial strains. These index patients can act as “super-contaminators,” driving extensive and persistent environmental contamination and amplifying the spread of their CRKP clones, suggesting that isolating “super-contaminators” should be a priority. In a study by Lerner et al., ^{Reference Lerner, Adler, Abu-Hanna, Cohen Percia, Kazma Matalon and Carmeli23} 18% of carriers accounted for 80% of environmental contamination, with individuals having high rectal concentrations of KPC-producing CRE being significantly more likely to act as super-spreaders compared to non-super-spreaders. Additionally, the absence of fecal incontinence was the only variable significantly associated with being a non-spreader.

In terms of patient-related factors, isolation should be prioritized for individuals identified as super-contaminators, particularly those with symptomatic infections and multiple sites of colonization. High-risk groups include immunocompromised patients, those with elevated bacterial or viral loads, individuals with diarrhea, and patients undergoing extensive medical interventions or invasive procedures such as catheterization, mechanical ventilation, or surgery. ^{Reference Blanco, O’Hara and Harris24,Reference Drees, Snydman and Schmid25}

Transmissibility and mode of transmission

Pathogen transmissibility is a key determinant in selecting appropriate isolation precautions. Highly infectious pathogens require stringent measures in healthcare settings due to their potential for rapid spread, from one host to another, and large-scale outbreaks, often leading to severe disease. Pathogens that travel through air often exhibit higher transmission rates than those requiring direct contact. Additionally, pathogens with prolonged environmental survival pose an increased risk of transmission. ^{Reference Wang, Prather and Sznitman26} Transmission rates, commonly expressed as the basic reproduction number (R), are influenced by factors such as modes of transmission, environmental stability, population density, infection control measures, and immunization coverage. ^{Reference Janik, Ceremuga, Niemcewicz and Bijak27} High vaccination coverage contributes to herd immunity, limiting the spread of highly contagious diseases. In contrast, emerging pathogens lacking herd immunity, such as SARS-CoV2, require stringent isolation precautions and prioritization. ^{Reference Clemente-Suárez, Hormeño-Holgado and Jiménez28,Reference Richard, Knauf and Lawrence29} Additionally, the rapid horizontal transfer of AMR genes via plasmids and transposons among enteric bacteria facilitates the persistence and dissemination of AMR. ^{Reference Uwanibe, Olawoye, Happi and Folarin30} Key drivers of transmission include specific resistance genes (e.g., ESBL, carbapenemase genes), high-risk clones such as K. pneumoniae ST147 and ST307, and genomic factors that enhance pathogen virulence and transmissibility. ^{Reference Kochan, Nozick and Medernach31}

The transmission rates of MDR pathogens can differ, and different mechanisms may drive patient-to-patient transmission chains. Studies have shown that ESBL-producing K. pneumoniae is an ESBL-producing Escherichia coli. In relation to bacterial factors, studies have demonstrated that environmental contamination occurs more frequently around patients colonized with Klebsiella spp. than those colonized with E. coli. These studies indicate that Klebsiella spp. can persist in the environment for extended periods because of their biofilm-forming ability. This environmental contamination facilitates the intra-hospital spread of Klebsiella spp., explaining their higher rates of cross-transmission and increased potential for outbreaks. ^{Reference Facciolà, Pellicanò and Visalli32–Reference Guet-Revillet, Le Monnier and Breton34} Person-to-person transmission of certain ESBL-producing E. coli is not a frequent occurrence in most hospital environments. ^{Reference Jones and Bradshaw35–Reference Gurieva, Dautzenberg, Gniadkowski, Derde, Bonten and Bootsma38} In a prospective multicenter study that included molecular genetic analyses assessing the impact of single-room contact precautions (SCP) on the hospital acquisition and transmission of E. coli resistant to third-generation cephalosporins (3GCR), with screening for intestinal colonization with 3GCR-E. coli using deep rectal swabs or stool samples within 72 hours of admission, weekly, and within 72 hours of discharge and bloodstream infection, no advantage was found for SCP compared to no contact precautions in preventing 3GCR-E. coli hospital acquisition and patient-to-patient transmission in a high-risk setting of hematological and oncological patients. ^{Reference Biehl, Higgins and Wille39} To this end, previous studies have reported that controlling ESBL-Enterobacterales entails far more difficulties compared to strategies targeted towards MRSA, owed to their different microbiological characteristics and epidemiology that facilitate environmental persistence and transmission. ^{Reference Zahar and Lesprit40}

In cases of isolation room shortages, de-escalation of isolation precautions can be guided by pathogen transmissibility. Chang et al. ^{Reference Chang, Im and Lee41} modified isolation protocols for patients colonized or infected with vancomycin-resistant Enterococci (VRE) following an observed increase in the incidence of HAIs caused by MDR, including carbapenem-resistant Enterobacterales (CRE). During the study period, VRE-positive patients were not isolated or cohorted, while hand hygiene, contact precautions (e.g., gloves and gowns), and environmental disinfection protocols remained unchanged. The study found no significant change in VRE bacteremia incidence with the relaxation of isolation measures, provided that other IPC measures were consistently implemented. Although some studies have reported an association between discontinuation of contact precautions and active screening programs for VRE and increased rates of VRE bacteremia, ^{Reference Johnstone, Shing and Saedi42} recent data suggest that contact precautions can be safely discontinued without a rise in MRSA or VRE infections. A survey by the Society for Healthcare Epidemiology of America Research Network (SRN), a consortium of acute care facilities, showed that while only 7% of SRN hospitals had discontinued using routine contact precautions in 2015, this figure increased to 35% by 2021. More than 90% of facilities that discontinued contact precautions cited scientific evidence as the primary rationale for their decisions. ^{Reference Martin, Morgan, Pryor and Bearman43} The decision to discontinue contact precautions should consider pathogen-related factors (e.g., surveillance samples, duration of colonization), patient-specific characteristics (such as symptoms, antibiotic use, length of hospital and intensive care unit stays), and institutional risk levels. Infection prevention and control leadership must regularly review and update policies, especially when there are changes in the epidemiology of concerning pathogens, such as during outbreaks or hyperendemic situations. ^{Reference Kleyman, Cupril-Nilson and Robinson44,Reference Banach, Bearman and Barnden45} Further research is still needed to confirm the safety of discontinuing contact precautions, explore alternative strategies for their implementation, and address potential patient harms in settings where they remain in use.

Environmental persistence and outbreak potential

Pathogens that can survive in environmental conditions for long periods of time pose a significant outbreak risk because they can persist on surfaces and equipment and facilitate transmission in healthcare environments.

Acinetobacter spp. is a common cause of HAIs with increasing frequency of MDR in recent years. Numerous outbreaks have been reported because of high environmental contamination rates and the ability for prolonged survival at these sites. ^{Reference Ahmed, Alp and Ulu-Kilic46,Reference Alp, Altun, Cevahir, Ersoy, Cakir and McLaws47} Acinetobacter spp. are known to persist on environmental surfaces for extended periods lasting several weeks. ^{Reference Weber, Rutala, Miller, Huslage and Sickbert-Bennett48} Additionally, studies have demonstrated the airborne dispersal of MDR A. baumannii. ^{Reference Yakupogullari, Otlu and Ersoy49} In a study by Wong et al., ^{Reference Wong, Chau and So50} they prioritized COVID-19 cases for isolation rooms during the pandemic and used open cubicles for patients with MDR A. baumannii. They implemented contact precautions, active screening of all hospitalized patients, cohort nursing, and environmental disinfection for new cases of MDR A. baumannii infections. Environmental and air samples were collected for MDR A. baumannii culture, and nosocomial transmission of A. baumannii was described. Their findings concluded that MDR A. baumannii could be dispersed through the air, as it was detected in air samples and contaminated hard-to-reach surfaces. They strongly recommended single-room isolation or the addition of a portable high-efficiency particulate air (HEPA) filter to conventionally designed open cubicles, particularly when the cubicles are fully occupied by patients with MDR A. baumannii. Moreover, they suggested that hospital renovation and redevelopment programs should include the installation of an air ventilation system with self-contained air inflow and exhaust within each cubicle, preferably with the door closed. Other studies have also shown that MRSA and carbapenemase-producing Enterobacterales can be spread through the air, highlighting the necessity for targeted measures to reduce the risk of airborne transmission in healthcare facilities. ^{Reference Wong, Chen and Kwok51}

Clostridioides difficile and norovirus are other common pathogens that can cause nosocomial outbreaks owing to environmental contamination. Owing to their ability to survive for prolonged periods on surfaces, environmental contamination plays an important role in their transmission in healthcare institutions and can thus be considered a priority. ^{Reference Weber, Rutala, Miller, Huslage and Sickbert-Bennett48} Although contact precautions are generally recommended to continue for the duration of illness in C. difficile infections and for at least 48 hours after symptom resolution or to manage institutional outbreaks in norovirus, a personalized approach may be appropriate for extending these precautions. Such an approach should consider patients with ongoing risk factors for colonization and/or contamination, such as advanced age, antibiotic use, incontinence, immunosuppression. ^{Reference Skyum, Pedersen and Andersen52,Reference White, Rajagopalan and Yoshikawa53}

Several factors influence the survival of bacteria in the environment. Although the type of bacterium and its inoculum size are key factors for survival, the material of the surface also plays a significant role in determining how long bacteria can persist. Neely ^{Reference Neely54} conducted a study on seven common gram-negative nosocomial bacteria and tested their survival on seven different materials. The findings revealed that the bacteria tended to survive longer on synthetic surfaces than on cotton, and even longer on plastic surfaces than on fabrics. Additionally, bacterial viability varied depending on the microorganism, with Pseudomonas surviving for a shorter duration than Enterobacterales and Acinetobacter spp. However, another experimental study that quantitatively investigated the impact of environmental conditions on the survival of 60 healthcare-associated MDR bacteria, including MRSA, VRE, K. pneumoniae, and A. baumannii, reported controversial results. Factors such as textile type, presence of nutrients, temperature, and humidity were examined in this study. The researchers found that Gram-positive MRSA and VRE had significantly higher survival rates on polyester compared to cotton, while Gram-negative MDR Acinetobacter spp showed significantly lower survival on polyester than on cotton. Additionally, MDR K.pneumoniae and MRSA survival rates increased significantly in nutrient broth compared to the control conditions, whereas the presence of nutrients did not significantly affect the of MDR Acinetobacter spp and VRE. ^{Reference Hanczvikkel and Tóth55} Understanding how different environmental conditions affect the survival of Gram-positive and Gram-negative bacteria is valuable for isolation measures and identifying outbreak sources.

Therefore, isolation precautions for multidrug-resistant (MDR) pathogens should be determined according to patient-specific factors, the types of procedures (i.e., small particle-forming procedures) performed, and the specific characteristics of the healthcare facility.

Hospital capacity and infrastructure

Facility characteristics are key determinants of the effectiveness of isolation measures. These include infrastructure, design, equipment, staffing levels, surveillance/screening strategies, and the local epidemiology of pathogens. Transmission rates of identical bacteria can vary depending on staff workload, facility design and infrastructure, screening strategies, antimicrobial stewardship, and patient population. Architectural features such as the separation of clean and contaminated areas, strategic patient flow, proper ventilation system in wards and isolation rooms with negative pressure ventilation are critical to prevent cross-contamination and controlling infectious agents, thus improving overall IPC outcomes. ^{Reference Nadi, Raisali, Jafari and Bayramzadeh56}