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PubMed2026

Factors associated with periprosthetic joint infection following total knee arthroplasty: an updated systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate factors associated with periprosthetic joint infection (PJI) following total knee arthroplasty (TKA), and thereby to provide evidence-based references for clinical prevention and perioperative risk stratification. METHODS: Computerized searches were conducted in the following databases from their inception until May 26, 2025: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Two researchers independently screened the literature, extracted data, and assessed study quality. The methodological quality was assessed using the Newcastle-Ottawa Scale. Quantitative synthesis was performed when at least two studies reported comparable exposure definitions and sufficient comparator information; otherwise, narrative synthesis was used. Review Manager 5.4 software was used for the primary analysis. This study is registered on PROSPERO (CRD420251079339). RESULTS: A total of 25 observational studies were included in the qualitative synthesis, of which 24 contributed to the primary quantitative synthesis. Quantitatively pooled factors associated with PJI included male sex (OR = 1.39, 95% CI 1.27-1.51), BMI ≥30 kg/m2 (OR = 5.72, 95% CI 2.65-12.36), prolonged operative time, type 2 diabetes mellitus (OR = 2.09, 95% CI 1.45-3.01), rheumatoid arthritis (OR = 2.64, 95% CI 1.38-5.02), smoking (OR = 1.65, 95% CI 1.34-2.04), blood transfusion (OR = 2.27, 95% CI 1.59-3.25), American Society of Anesthesiologists score ≥3 (OR = 2.73, 95% CI 1.02-7.32), history of hormone therapy (OR = 4.88, 95% CI 2.90-8.22), postoperative urinary tract infection (OR = 3.59, 95% CI 1.15-11.21), intraoperative blood loss >200 ml (OR = 1.51, 95% CI 1.03-2.22), postoperative drainage tube placement duration ≥24 h (OR = 2.23, 95% CI 1.50-3.32), preoperative anemia (OR = 1.82, 95% CI 1.67-1.99), and combined pulmonary disease (OR = 5.54, 95% CI 1.93-15.96). Age was narratively summarized because its classification differed substantially across studies. CONCLUSION: Multiple demographic, comorbidity-related, and perioperative factors were associated with PJI after TKA. However, because the included studies were observational and clinically heterogeneous, these findings should be interpreted as associations rather than causal effects. Optimization of modifiable factors may help reduce the burden of PJI, but further prospective studies using standardized PJI definitions and adjusted effect estimates are required.

Humans↗
PubMed2026

The diagnostic potential of combined quantitative polymerase chain reaction and next-generation sequencing using the same primers for periprosthetic joint infection.

Next-generation sequencing (NGS) enables the detection of specific pathogens unidentifiable by conventional cultures, but its application in orthopedics remains inconsistent due to background contamination and irreproducible findings. This study evaluated the diagnostic performance of a novel workflow combining broad-range 16S rRNA gene quantitative PCR (qPCR) screening with downstream NGS, focusing on bacterial biomass thresholds. The qPCR assay demonstrated excellent intrarater reliability, with an intraclass correlation coefficient (ICC) of 0.961 (95% confidence interval, 0.881 to 0.997). Based on serially diluted positive controls, a quantitative threshold of 10⁵ CFU/mL was established as the minimum concentration required for the consistent detection of fastidious taxa, such as Escherichia coli. When evaluated against conventional cultures using 95 sonicate fluid and 276 pre/intraoperative tissue samples, the qPCR assay achieved a sensitivity of 80% and a specificity of 72%. Subsequent NGS sequencing of 26 clinical samples and 9 controls showed concordance in 4 of 6 culture-positive infected cases with NGS taxonomy, whereas the remaining discrepancies were likely attributable to culture-based phenotypic misidentification. Notably, among the qPCR-positive cases, three were culture-negative, including two hip prosthesis loosening cases exhibiting polymicrobial profiles, and one post-traumatic osteoarthritis case harboring low-level Staphylococcus. Crucially, this post-traumatic patient developed delayed periprosthetic joint infection (PJI) 2 years post-surgery, with cultures identifying Staphylococcus previously detected by the initial NGS analysis. Integrating qPCR screening with targeted NGS effectively refines pathogen identification, filters environmental artifacts, and overcomes the diagnostic limitations of culture-negative infections in orthopedic practice.IMPORTANCENext-generation sequencing (NGS) enables the detection of specific pathogens in clinical samples that are not identifiable by conventional methods. However, NGS applications in orthopedics have not been quantitatively evaluated, and findings have been inconsistent owing to contaminants and the presence of non-credible causative organisms. These factors primarily stem from the failure to evaluate low-biomass samples and the absence of proper controls, such as negative controls or mock community DNA samples. This study demonstrates that interpreting results from low-biomass samples requires careful consideration because NGS relies on relative bacterial abundances; distinguishing likely pathogens from contaminants is particularly challenging when bacterial loads are low. We demonstrated that combining NGS with quantitative PCR (qPCR) and applying a Cq cutoff can reduce false positives.

Humans↗
PubMed2025

Bacterial skin colonization with a specific Cutibacterium avidum clade as a risk factor for periprosthetic joint infections-a multicenter study.

Cutibacterium avidum is increasingly recognized as a causative agent of periprosthetic joint infections (PJIs), yet data on its pathogenic potential and distinguishing features from commensal strains remain limited. In this multicenter study, we compared 11 C. avidum isolates from PJIs with 32 isolates from healthy skin collected across four European hospitals. We investigated phylogenetic relationships, antibiotic susceptibility, biofilm formation, and bacterial fitness. Phylogenomic analysis revealed two main clades within the C. avidum population. All PJI isolates belonged exclusively to Clade 1, which also included skin isolates. Within Clade 1, gene content analysis showed no consistent genetic differences between PJI and skin isolates. All isolates exhibited moderate to strong biofilm formation, with no significant differences in either data set. Minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC) values were low and largely concordant, while minimal biofilm eradication concentration (MBEC) values were elevated for all antibiotics except rifampin. One isolate was resistant to clindamycin due to the erm(X) gene. Rifampin consistently showed the lowest MIC, minimal bactericidal concentration, MBIC, and MBEC values. Bacterial fitness, assessed via bacterial quantitative fitness analysis, was significantly lower in PJI isolates compared to skin isolates when all strains were analyzed (P = 0.039), but this difference was not statistically significant when restricted to Clade 1. In conclusion, C. avidum isolates are strong biofilm producers irrespective of clinical origin. PJI isolates are restricted to a single phylogenetic clade, yet lack distinct biofilm or fitness traits within that clade, suggesting that multiple Clade 1 strains may have the potential to cause PJIs. IMPORTANCE Cutibacterium avidum has long been considered a skin commensal, but it is increasingly associated with prosthetic joint infections (PJIs). Despite its clinical emergence, little is known about its virulence potential or how invasive strains differ from commensal ones. This multicenter study provides the most comprehensive comparative analysis to date, integrating phenotypic and genomic data from both PJI-associated and skin-derived isolates. We show that all isolates are strong biofilm formers and that invasive isolates exhibit reduced growth fitness-a phenotype linked to persistence and treatment failure in other pathogens. Notably, all PJI isolates belonged to a single phylogenetic clade, suggesting that specific lineages of C. avidum may be more likely to cause infection. These findings help clarify the biology of this emerging pathogen and provide a foundation for improved diagnostics, susceptibility testing, and future infection prevention and treatment strategies.

Biofilms↗
PubMed2026

Chronic suppression of a multidrug-resistant Pseudomonas aeruginosa in prosthetic joint infection using personalized bacteriophage treatment.

Multidrug resistant (MDR) bacterial infections without antibiotic options are a public health emergency. Infections associated with medical implants serve as an example. Conventional antibiotics have limited ability to eradicate these infections as they are associated with antibiotic-tolerant biofilms. Here, we report the use of bacteriophage therapy for the treatment of a MDR, non-operable Pseudomonas aeruginosa periprosthetic joint infection that had failed multiple antibiotic and surgical interventions. Treatment with intermittent bacteriophage therapy alone without antibiotics over a 2 year time period resulted in clinical resolution of the infection, but not microbiological eradication. Bacteriophage therapy established this control, in part, by altering virulence as defined by disease severity and symptoms and disrupting biofilm. Whole genome sequencing demonstrated the continued presence of bacteriophage during treatment. This provides preliminary evidence that bacteriophage therapy can be used to treat MDR infections in salvage cases when surgical and antibiotic options do not exist.

Humans↗