Population aging is a global phenomenon, with a rapid increase in individuals aged ≥65 years, leading to a higher burden on healthcare systems [1]. Frailty, defined as a state of increased vulnerability due to diminished physiological reserve, has emerged as a key determinant of adverse outcomes in elderly patients [2]. The Clinical Frailty Scale (CFS), a validated tool ranging from 1 (very fit) to 9 (terminally ill), provides a rapid bedside assessment of frailty status [3].

Hospitalized older adults are particularly susceptible to healthcare-associated infections (HAIs), including urinary tract infections, pneumonia, and bloodstream infections associated with devices [4]. These infections contribute significantly to morbidity, mortality, prolonged hospital stay, and healthcare costs [5]. Furthermore, the emergence of multidrug-resistant organisms (MDROs) has complicated the management of infections in this population [6].

Frailty may predispose individuals to infections through mechanisms such as immunosenescence, chronic inflammation (“inflammaging”), and microbiome dysbiosis [7]. These biological changes impair immune response and increase susceptibility to colonization by resistant organisms [8]. Additionally, frail individuals often have increased healthcare exposure, invasive procedures, and antibiotic use, further elevating MDRO risk [9].

Recent evidence suggests that frailty is associated with higher rates of antibiotic-resistant infections, with frail patients demonstrating up to threefold increased odds of resistant isolates [10]. Similarly, frail patients in intensive care settings are more likely to harbor MDRO pathogens despite comparable infection rates to non-frail individuals [11].

Despite growing evidence, there is limited prospective data examining the combined relationship between frailty, HAIs, and MDRO colonization in hospitalized elderly populations, particularly in developing countries. Understanding this association is crucial for improving infection control strategies and optimizing antimicrobial stewardship.

This study aims to evaluate the association between CFS and the occurrence of HAIs and MDRO colonization among hospitalized older adults.

This prospective observational study was conducted over a period of 12 months from December 2024 to November 2025 in the Department of Microbiology at a tertiary care teaching hospital. The study aimed to evaluate the association between frailty, as assessed by the Clinical Frailty Scale (CFS), and the occurrence of healthcare-associated infections (HAIs) as well as multidrug-resistant organism (MDRO) colonization in hospitalized older adults.

A total of 120 patients aged 65 years and above who were admitted to the medical wards and had a hospital stay exceeding 48 hours were enrolled consecutively. Patients who were terminally ill with an expected survival of less than 48 hours, those receiving active chemotherapy or other forms of severe immunosuppression, and individuals with incomplete clinical or microbiological data were excluded from the study. Written informed consent was obtained from all participants or their legally authorized representatives. The study protocol was approved by the Institutional Ethics Committee and conducted in accordance with the Declaration of Helsinki.

Frailty assessment was performed within 24 hours of admission using the Clinical Frailty Scale, a validated 9-point tool that categorizes patients based on their functional status and comorbid burden. Based on the CFS score, patients were classified into three groups: non-frail (scores 1–3), pre-frail (scores 4–5), and frail (scores 6–9).

Baseline demographic and clinical data were collected using a structured case record form. Variables included age, gender, comorbidities (such as diabetes mellitus, hypertension, chronic kidney disease, and chronic obstructive pulmonary disease), prior hospitalizations, recent antibiotic use (within the past 3 months), and use of invasive devices including urinary catheters, central venous lines, and mechanical ventilation. Length of hospital stay and clinical outcomes were also recorded.

HAIs are defined as infections acquired in the hospital by a patient admitted for a reason other than the infection in context with the symptoms appearing atleast after 48 hours of admission in accordance with standard Centers for Disease Control and Prevention (CDC) criteria. These included catheter-associated urinary tract infections, ventilator associated pneumonia, central line associated bloodstream infections, and surgical site infections where applicable. Diagnosis was based on a combination of clinical features, laboratory parameters, and microbiological confirmation using a standardised form.

Microbiological evaluation was performed for all patients suspected of infection as well as for screening of MDRO colonization. Samples including blood, urine, sputum, and pus aspirate/tissue/wound swabs were collected under aseptic precautions and processed using standard microbiological techniques. Colonization with multidrug-resistant organisms (MDROs) was assessed by microbiological screening of rectal swabs or stool specimens, along with nasal swabs. Identification of organisms was carried out using conventional biochemical methods and Vitek 2 system . Antimicrobial susceptibility testing was performed and interpreted according to Clinical and Laboratory Standards Institute M100, 2025. Multidrug-resistant organisms were defined as isolates resistant to at least one agent in three or more antimicrobial classes.

The primary outcome measures were the incidence of healthcare-associated infections and the prevalence of MDRO colonization across different frailty categories. Secondary outcomes included identification of risk factors associated with these conditions.

Statistical analysis was performed using standard statistical software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. The association between frailty status and outcomes was analyzed using the chi-square test or Fisher’s exact test as appropriate. Multivariate logistic regression analysis was conducted to identify independent predictors of HAIs and MDRO colonization, adjusting for potential confounders such as age, comorbidities, antibiotic exposure, and device use. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A p-value of less than 0.05 was considered statistically significant.

Efforts were made to minimize bias by standardizing data collection procedures and ensuring uniform diagnostic criteria. All data were anonymized to maintain patient confidentiality.

A total of 120 hospitalized older adults were included in the study. The mean age of the study population was 72.6 ± 6.5 years, with a slight male predominance (male: female ratio = 1.2:1). Based on the Clinical Frailty Scale (CFS), 39 patients (32.5%) were categorized as non-frail, 40 (33.3%) as pre-frail, and 41 (34.2%) as frail.

Frailty Distribution and Baseline Characteristics

The distribution of frailty was relatively uniform across the study population. Comorbid conditions such as diabetes mellitus (48.3%), hypertension (56.7%), and chronic kidney disease (18.3%) were more frequently observed among frail individuals compared to non-frail patients. Additionally, frail patients had longer hospital stays and higher utilization of invasive devices.

Table 1: Baseline Characteristics and Frailty Distribution

Healthcare-Associated Infections

The overall incidence of healthcare-associated infections (HAIs) in the study population was 28.3% (34/120). A significant increasing trend in HAI occurrence was observed with higher frailty levels. Frail patients had the highest incidence of HAIs (45.5%), followed by pre-frail (27.5%) and non-frail individuals (12.8%). This difference was statistically significant (p < 0.001).

Among the types of infections, catheter associated urinary tract infections were the most common (38%), followed by ventilator associated pneumonia (32%), central line associated bloodstream infections (18%), and other infections (12%).

Table 2: Association Between Frailty and Healthcare-Associated Infections

Multidrug-Resistant Organism Colonization

The overall prevalence of MDRO colonization was 34.16% (41/120). Similar to HAIs, MDRO colonization increased significantly with higher frailty scores. Frail patients showed a markedly higher prevalence (56.1%) compared to pre-frail (30%) and non-frail (15.38%) groups (p < 0.001).

Among MDRO isolates, ESBL-producing Enterobacterales were the most common (46%), followed by MRSA (32%) and carbapenem-resistant organisms (22%).

Table 3: Association Between Frailty and MDRO Colonization

Predictors of HAIs and MDRO Colonization

Multivariate logistic regression analysis revealed that frailty was an independent predictor of both healthcare-associated infections and MDRO colonization. Frail patients had a 3.1-fold increased risk of developing HAIs (95% CI: 1.8–5.4) and a 3.8-fold increased risk of MDRO colonization (95% CI: 2.1–6.7).

Other significant predictors included prior antibiotic exposure, prolonged hospital stay (>7 days), and use of invasive devices.

Table 4: Multivariate Logistic Regression Analysis for Predictors of HAIs and MDRO Colonization

The present study demonstrates a significant and clinically relevant association between increasing frailty, as assessed by the Clinical Frailty Scale (CFS), and the risk of healthcare-associated infections (HAIs) as well as multidrug-resistant organism (MDRO) colonization among hospitalized older adults. The findings indicate that frailty is not merely a marker of aging but an independent predictor of infection-related vulnerability, supporting its integration into routine clinical risk stratification.

The observed prevalence of HAIs (28.3%) in this study aligns with previously reported rates in hospitalized elderly populations, which range between 20% and 35% depending on comorbidity burden and healthcare exposure [4,5]. A clear gradient was noted across frailty categories, with frail individuals demonstrating nearly fourfold higher infection rates compared to non-frail patients. This pattern underscores the progressive decline in host defense mechanisms associated with frailty. Age-related immune dysfunction, characterized by impaired innate and adaptive immune responses, contributes significantly to increased susceptibility to infections in this group [16,17].

One of the key biological mechanisms linking frailty and infection risk is “inflammaging,” a chronic low-grade inflammatory state that disrupts immune homeostasis and reduces the ability to mount effective responses to pathogens [7]. Additionally, frailty is associated with sarcopenia, malnutrition, and reduced physiological reserves, all of which further compromise immune competence. These factors collectively explain the higher burden of infections observed in frail patients.

The study also demonstrated a strong association between frailty and MDRO colonization, with more than half of the frail patients harboring resistant organisms. This finding is consistent with previous reports indicating that elderly individuals, particularly those with functional decline, have a higher likelihood of colonization with resistant pathogens [12,13]. The prevalence of MDRO colonization in this study (34.2%) is comparable to rates reported in hospital-based and long-term care settings, where colonization rates often exceed 30% [13].

Several factors may explain the increased MDRO burden in frail individuals. First, frail patients are more likely to have repeated healthcare exposures, including frequent hospitalizations and prolonged stays, which increase the risk of acquiring resistant organisms [14-17]. Second, the higher use of invasive devices such as urinary catheters and central lines facilitates microbial entry and biofilm formation, promoting colonization and infection. Third, prior antibiotic exposure, which was identified as a significant predictor in this study, plays a crucial role in selecting resistant strains and disrupting normal microbial flora [18].

Importantly, colonization with MDROs is not merely a microbiological finding but has significant clinical implications. It has been reported that a substantial proportion of colonized individuals subsequently develop infections caused by the same resistant organisms, particularly in the presence of invasive procedures or immunosuppression [15]. Therefore, early identification of colonized patients, especially those who are frail, can enable targeted infection prevention strategies.

The independent predictive value of frailty observed in multivariate analysis reinforces the need to incorporate frailty assessment into routine hospital practice. The CFS is a simple and practical tool that can be easily applied at the bedside without requiring extensive resources [3]. Its use can help identify high-risk individuals who may benefit from enhanced infection control measures, closer monitoring, and tailored antimicrobial therapy.

From a clinical standpoint, these findings have important implications for antimicrobial stewardship. Frailty-based risk stratification may help guide empiric antibiotic selection, reducing the unnecessary use of broad-spectrum agents in low-risk patients while ensuring adequate coverage in high-risk individuals [10]. This approach can contribute to reducing the emergence of antimicrobial resistance, which remains a major global health challenge [6,19,20].

Furthermore, the study highlights the importance of preventive strategies in frail populations. Measures such as minimizing unnecessary catheter use, optimizing nutrition, early mobilization, and strict adherence to infection control protocols can significantly reduce infection risk. In addition, screening for MDRO colonization in high-risk patients may allow for early implementation of contact precautions and targeted decolonization strategies where appropriate.

The findings also emphasize the need for a multidisciplinary approach to geriatric care. Frailty is a complex, multidimensional condition that requires coordinated management involving physicians, nurses, physiotherapists, and infection control teams. Integrating frailty assessment into clinical workflows can facilitate personalized care planning and improve overall patient outcomes.

Despite its strengths, including a prospective design and standardized assessment methods, the study has certain limitations. Being a single-center study, the findings may not be generalizable to all healthcare settings. Additionally, the sample size, although adequate for statistical analysis, may limit the detection of less common outcomes. Future multicentric studies with larger cohorts and longer follow-up are needed to validate these findings and explore the impact of frailty-based interventions on infection outcomes.

Frailty, as measured by the Clinical Frailty Scale, is a significant independent predictor of healthcare-associated infections and multidrug-resistant organism colonization in hospitalized older adults. Routine frailty assessment should be integrated into clinical practice to enhance infection risk stratification and guide antimicrobial stewardship strategies.

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