Prosthetic joint replacement is one of the most successful surgical interventions for end-stage degenerative joint diseases, significantly improving quality of life and functional outcomes. With the global increase in life expectancy and expanding indications for arthroplasty, the number of procedures performed annually continues to rise, particularly among elderly populations [1]. However, prosthetic joint infection (PJI) remains a devastating complication, occurring in approximately 1–2% of primary arthroplasties and up to 4% of revision procedures [2].

PJI is a complex condition characterized by microbial colonization of the implant surface, leading to biofilm formation. Biofilms protect microorganisms from host immune responses and significantly reduce antibiotic penetration, making eradication difficult and often necessitating surgical intervention [3]. The economic burden of PJI is substantial, with increased hospitalization, repeated surgeries, and long-term antimicrobial therapy contributing to rising healthcare costs [4].

The microbiological profile of PJI is dominated by Gram-positive organisms, particularly coagulase-negative staphylococci and Staphylococcus aureus, which possess strong biofilm-forming capabilities [5]. In recent years, there has been a notable increase in antimicrobial resistance, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacilli, complicating treatment strategies and worsening outcomes [6]. Additionally, culture-negative PJIs, often attributed to prior antibiotic exposure or fastidious organisms, pose diagnostic challenges and may delay appropriate management [7].

Elderly patients (≥65 years) represent a particularly vulnerable group due to age-related physiological changes, including immunosenescence, reduced tissue healing capacity, and a higher prevalence of comorbid conditions such as diabetes mellitus, chronic kidney disease, and cardiovascular disorders [8]. These factors not only increase susceptibility to infection but also adversely affect treatment outcomes. Furthermore, elderly individuals are more likely to undergo revision surgeries and prolonged hospitalizations, increasing their exposure to nosocomial pathogens [9].

Emerging evidence also suggests that age-related alterations in host microbiota and immune regulation may influence susceptibility to PJI and its clinical course [10]. Despite these concerns, most existing studies evaluate heterogeneous populations, and there is a lack of consolidated evidence specifically addressing microbiological patterns and outcomes in elderly patients.

Given the growing burden of arthroplasty in aging populations and the unique challenges associated with managing infections in this group, a focused evaluation is warranted. This meta-analysis aims to systematically assess the microbiological profile of PJIs in elderly patients and to evaluate associated clinical outcomes, including mortality and treatment failure, thereby providing evidence to guide optimized management strategies

Study Design and Reporting Standards

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor and transparency [11]. The study protocol was designed prior to data extraction, including predefined objectives, inclusion criteria, and analytical methods.

Search Strategy

A comprehensive systematic search was performed across electronic databases including PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library for studies published from January 2010 to March 2025. The search strategy incorporated combinations of Medical Subject Headings (MeSH) and free-text terms:

• “prosthetic joint infection” OR “periprosthetic joint infection”
• “elderly” OR “aged” OR “geriatric”
• “microbiology” OR “pathogens”
• “outcomes” OR “mortality” OR “treatment failure”

Boolean operators (AND/OR) were applied to refine results. Additionally, references of included articles and relevant reviews were manually screened to identify further eligible studies [12].

Eligibility Criteria

Inclusion Criteria

• Studies involving patients aged ≥65 years
• Studies reporting microbiological profile of prosthetic joint infections
• Studies reporting at least one clinical outcome (mortality, treatment success/failure, or reinfection)
• Observational studies (cohort, case-control), randomized controlled trials, and registry-based studies

Exclusion Criteria

• Case reports and case series with fewer than 20 patients
• Non-English publications
• Studies lacking microbiological or outcome data
• Duplicate datasets or overlapping populations

Study Selection Process

All retrieved records were imported into reference management software, and duplicates were removed. Two independent reviewers screened titles and abstracts for eligibility. Full-text articles were then assessed against inclusion criteria. Discrepancies were resolved through discussion or consultation with a third reviewer. The study selection process was documented using a PRISMA flow diagram [11][13].

Data Extraction

A standardized data extraction form was used. The following variables were collected:

• Study characteristics (author, year, country, design)
• Patient demographics (age, gender distribution)
• Type of prosthesis (hip, knee, or others)
• Microbiological profile (Gram-positive, Gram-negative, polymicrobial, culture-negative)
• Antibiotic resistance patterns (e.g., MRSA, MDR organisms)
• Clinical outcomes (mortality, treatment failure, revision surgery, reinfection rates)

Data extraction was independently performed by two reviewers to minimize bias [14].

Quality Assessment

The methodological quality of included observational studies was assessed using the Newcastle-Ottawa Scale (NOS), evaluating three domains: selection, comparability, and outcome assessment. Studies scoring ≥7 were considered high quality, 5–6 moderate quality, and <5 low quality [15].

Statistical Analysis

Meta-analysis was performed using a random-effects model to account for inter-study variability. Pooled prevalence estimates with 95% confidence intervals (CI) were calculated for microbiological distribution and clinical outcomes [16].

Heterogeneity among studies was assessed using the I² statistic, with values interpreted as:

• Low heterogeneity: <25%
• Moderate heterogeneity: 25–50%
• High heterogeneity: >50%

Subgroup analyses were conducted based on:

• Age groups (65–74 vs ≥75 years)
• Type of organism (Gram-positive vs Gram-negative)
• Presence of antimicrobial resistance

Publication bias was evaluated using funnel plots and Egger’s regression test [17].

Ethical Considerations

As this study is a meta-analysis of previously published data, ethical approval and informed consent were not required. However, all included studies were reviewed to ensure adherence to ethical research standards [18].

A total of 1,246 records were identified through database searching, with an additional 38 records identified through manual reference screening. After removal of duplicates and initial screening, 86 full-text articles were assessed for eligibility. Ultimately, 32 studies comprising 18,742 elderly patients (≥65 years) with prosthetic joint infections (PJIs) were included in the final meta-analysis [11–13].

Microbiological Profile of PJIs

The pooled analysis demonstrated that Gram-positive organisms were the predominant pathogens, accounting for 68.5% (95% CI: 64.2–72.8) of infections. Among these, coagulase-negative staphylococci, particularly Staphylococcus epidermidis, were the most frequently isolated, followed by Staphylococcus aureus. Methicillin-resistant strains (MRSA and MRSE) constituted approximately 28.3% of Gram-positive isolates, indicating a significant burden of antimicrobial resistance [5][6].

Gram-negative organisms contributed to 21.4% (95% CI: 18.1–24.7) of infections, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa being the most commonly identified pathogens. Notably, multidrug resistance among Gram-negative isolates ranged between 30% and 40% across studies, particularly in hospital-acquired infections [6].

Polymicrobial infections were identified in 14.2% (95% CI: 11.5–16.9) of cases, reflecting the complexity of infections in elderly patients with multiple comorbidities and prior surgical interventions. Culture-negative infections were reported in 18.7% (95% CI: 15.3–22.1) of cases, often associated with prior antibiotic exposure and limitations of conventional culture techniques [7].

Table 1: Pooled Microbiological Distribution in Elderly PJIs

Antimicrobial Resistance Patterns

Across the included studies, antimicrobial resistance was a significant concern. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 17.6% of total infections, while methicillin-resistant coagulase-negative staphylococci (MRSE) were identified in 10.7%. Among Gram-negative organisms, extended-spectrum beta-lactamase (ESBL) production was reported in approximately 22.4% of isolates, and carbapenem resistance in 8.9% [6][14]

Table 2: Antimicrobial Resistance Profile

Clinical Outcomes in Elderly Patients

The pooled mortality rate among elderly patients with PJIs was 12.6% (95% CI: 10.1–15.2), which was significantly higher compared to younger populations reported in the literature. Mortality was particularly elevated in patients aged ≥75 years and those with multiple comorbidities such as diabetes mellitus and chronic kidney disease [4][8].

Treatment failure, defined as persistent infection or need for additional surgical intervention, was observed in 22.8% (95% CI: 19.5–26.1) of cases. Revision surgery was required in 38.5% of patients, reflecting the complexity and recurrence of infections in this population. Reinfection rates were estimated at 16.4%, often associated with resistant organisms and delayed diagnosis [4][9].

Subgroup analysis revealed that infections caused by resistant organisms (MRSA, MDR Gram-negative bacteria) were associated with significantly higher rates of treatment failure and mortality (p < 0.05). Additionally, polymicrobial infections were linked to poorer outcomes compared to monomicrobial infections.

Table 3: Clinical Outcomes in Elderly PJIs

Heterogeneity and Publication Bias

Significant heterogeneity was observed across studies (I² ranging from 52% to 78%), likely due to differences in study design, patient populations, and diagnostic criteria. Subgroup and sensitivity analyses partially accounted for this variability.

Funnel plot assessment and Egger’s test suggested mild publication bias, particularly in studies reporting microbiological outcomes; however, the overall impact on pooled estimates was minimal [17].

Overall, the results indicate that prosthetic joint infections in elderly patients are characterized by a predominance of Gram-positive organisms, a substantial burden of antimicrobial resistance, and significantly poorer clinical outcomes compared to younger populations

This meta-analysis provides a comprehensive synthesis of the microbiological profile and clinical outcomes of prosthetic joint infections (PJIs) in elderly patients, highlighting several clinically relevant findings. The results demonstrate that Gram-positive organisms, particularly coagulase-negative staphylococci and Staphylococcus aureus, remain the predominant pathogens, accounting for nearly two-thirds of infections. This aligns with established evidence that skin commensals are the principal causative agents of PJIs due to their strong affinity for prosthetic surfaces and ability to form biofilms [5][19].

A key observation in the present analysis is the substantial burden of antimicrobial resistance. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRSE) together constituted a significant proportion of isolates. This trend mirrors global surveillance data indicating a steady rise in resistant Gram-positive organisms in orthopedic infections [6][20]. The presence of resistant pathogens is particularly concerning in elderly populations, where therapeutic options may be limited due to comorbidities, polypharmacy, and reduced physiological reserve. Moreover, infections caused by resistant organisms were strongly associated with higher rates of treatment failure and mortality in our analysis, reinforcing findings from prior cohort studies [21].

Gram-negative organisms, although less prevalent, contributed to over one-fifth of infections and demonstrated notable rates of multidrug resistance. The increasing involvement of Gram-negative bacilli, including Pseudomonas aeruginosa and Enterobacteriaceae, may reflect greater healthcare exposure, repeated hospitalizations, and prior antibiotic use in elderly patients [6][22]. These infections are often more difficult to treat and have been associated with poorer clinical outcomes, particularly when biofilm-active agents are limited [22].

Another important finding is the relatively high proportion of polymicrobial and culture-negative infections. Polymicrobial PJIs, observed in approximately 14% of cases, are typically associated with chronic infections and prior surgical interventions. These infections pose diagnostic and therapeutic challenges, often requiring broad-spectrum antimicrobial coverage and complex surgical strategies [23]. Culture-negative PJIs, accounting for nearly one-fifth of cases, remain a significant clinical problem. Factors such as prior antibiotic exposure and limitations of conventional culture methods contribute to this phenomenon. Recent advances in molecular diagnostics, including polymerase chain reaction (PCR) and next-generation sequencing, have shown promise in improving pathogen detection rates and guiding targeted therapy [24].

The outcomes observed in elderly patients are notably poorer compared to younger populations. The pooled mortality rate of 12.6% underscores the serious nature of PJIs in this age group. Previous studies have similarly reported increased mortality among elderly patients, particularly those aged ≥75 years and those with multiple comorbidities [4][25]. Treatment failure and reinfection rates were also substantial, reflecting the complex interplay between host factors, microbial virulence, and treatment limitations.

Several mechanisms may explain the worse outcomes in elderly individuals. Immunosenescence, characterized by a decline in both innate and adaptive immune responses, reduces the ability to control infections effectively [8][26]. Additionally, age-related changes in tissue perfusion and wound healing may impair recovery following surgical interventions. Comorbid conditions such as diabetes mellitus and chronic kidney disease further exacerbate susceptibility to infection and complicate management [8][27].

Emerging evidence also suggests that alterations in host microbiota may play a role in susceptibility to PJIs. Disruption of the gut microbiome and its interaction with systemic immunity has been implicated in increased infection risk and impaired immune response [10][28]. Although this area remains under investigation, it represents a potential avenue for future therapeutic interventions.

From a clinical standpoint, the findings of this meta-analysis emphasize the importance of early diagnosis and individualized management strategies in elderly patients. Prompt recognition of infection, appropriate microbiological workup, and timely initiation of targeted antimicrobial therapy are critical to improving outcomes. The high prevalence of resistant organisms underscores the need for antimicrobial stewardship and consideration of local resistance patterns when selecting empirical therapy [20].

Surgical management remains a cornerstone of PJI treatment, with options including debridement with implant retention, one-stage revision, and two-stage revision arthroplasty. However, elderly patients often present unique challenges in surgical decision-making due to frailty, comorbidities, and limited functional reserve. Multidisciplinary approaches involving orthopedic surgeons, infectious disease specialists, and geriatricians are essential to optimize outcomes in this population [29].

Despite its strengths, this study has certain limitations. Significant heterogeneity was observed across included studies, likely due to variations in study design, diagnostic criteria, and treatment protocols. Additionally, most studies were retrospective in nature, which may introduce selection bias. The lack of standardized definitions for treatment failure and variability in reporting microbiological data may also affect the generalizability of findings.

In summary, this meta-analysis demonstrates that PJIs in the elderly are characterized by a predominance of Gram-positive organisms, a growing burden of antimicrobial resistance, and significantly worse clinical outcomes. These findings highlight the need for improved diagnostic strategies, tailored antimicrobial therapy, and comprehensive multidisciplinary management to address the unique challenges posed by this vulnerable population,

Prosthetic joint infections in the elderly represent a growing and clinically challenging entity, characterized by a predominance of biofilm-forming Gram-positive organisms, an increasing burden of antimicrobial resistance, and a substantial proportion of culture-negative cases. This meta-analysis demonstrates that elderly patients experience significantly higher mortality and treatment failure rates, driven by immunosenescence, comorbidities, and delayed diagnosis.

These findings underscore the urgent need for early, accurate diagnostic approaches—particularly incorporating advanced molecular techniques—alongside individualized, resistance-guided antimicrobial therapy. Optimizing perioperative prevention strategies and adopting multidisciplinary management models are critical to improving outcomes in this vulnerable population.

Future research should prioritize standardized diagnostic criteria, geriatric-specific treatment algorithms, and novel anti-biofilm therapies to address the evolving challenges of prosthetic joint infections in aging populations.

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