Identification of Infections in Hip Arthroplasty Loosening.

Istituto Ortopedico Rizzoli

Status: Completed

Conditions: Loosening, Prosthesis

Treatments: Other: Characterization of gut microbiota; Other: Characterization of oral microbiota; Other: Characterization of tissue microbiota; Diagnostic Test: Microbiological analysis of periprosthetic tissue; Diagnostic Test: Histological analysis of periprosthetic tissue

Study type: Observational

Funder types: Other

Identifiers

NCT04773054

TAS-ASEPTIC

Details and patient eligibility

About

Recent data showed that the rate of periprosthetic infections in patients undergoing a hip arthroplasty revision for aseptic loosening is higher than what can be ascertained with conventional methods.

The study aims to assess the adequacy of next-generation sequencing of 16s ribosomal ribonucleic acid (rRNA) gene amplicons for identifying occult infections and improving the diagnostic workup. Moreover, additional testing has been planned in order to increase knowledge on the etiopathogenesis of infection.

Full description

Periprosthetic infection following hip arthroplasty is one of the main causes of implant failure that leads to multiple surgical interventions, prolonged hospitalization, and higher complication rate and mortality.

Recent data prove that the rate of periprosthetic infections is higher than what can be ascertained with conventional techniques and highlight as analytical methods that allow an early and accurate diagnosis may help clinicians identify effective treatment and mitigate the devastating consequences.

New technologies based on culture-independent assays, i.e., the next-generation sequencing (NGS) of 16s rRNA gene amplicons, have entered medical microbiology as an alternative to traditional bacterial identification methods. NGS has been proven to detect microorganisms in culture-negative periprosthetic joint infection and seems to be a valid adjunct in identifying causative pathogens in samples from patients undergoing a hip arthroplasty revision for aseptic loosening.

The microbiota profiling using NGS may also help identify patients prone to develop infections. In predisposing clinical conditions, i.e., obesity and diabetes, the metabolic and nutritional alterations modify the composition and the immunomodulatory properties of intestinal microbiota. Saprophytic, non-pathogenic microorganisms usually found in the intestine and oral cavity can be transferred to other areas becoming a potential source of periprosthetic infection.

Additionally, microorganisms may live in the periprosthetic microenvironment without giving signs of overt infection. However, bacterial products, i.e., "microbe-associated molecular patterns" (MAMPs) or "pathogen-associated molecular patterns "(PAMPs), adhere to the implant surface or the wear particles and may elicit a local inflammatory response characterized by the presence of cells capable of producing cytokines that promote osteoclastogenesis, periprosthetic resorption and consequent loosening of the implant.

In summary, the current knowledge suggests that the hip arthroplasty loosening, classified as aseptic according to the preoperative clinical and laboratory investigations, could be directly or indirectly associated with infectious pathogenesis even if the microbial cultures on periprosthetic tissues are negative.

The investigators designed a small-scale study to assess the adequacy of NGS for identifying occult infections and improving the diagnostic workup in patients undergoing a hip arthroplasty revision for aseptic loosening. Moreover, additional testing has been planned to enhance knowledge on the role of unusual or difficult-to-cultivate microorganisms in the etiopathogenesis of implant failure.

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Hip arthroplasty revision for aseptic loosening, diagnosis determined as probable according to the following criteria:

• pain and/or functional impairment;
• radiographic signs of osteolysis following wear of the implant components, or cortical reaction, or periprosthetic bone resorption;
• negative evaluation by the infectious disease specialist.

Exclusion criteria

• presence of a sinus tract communicating with the arthroplasty;
• bacteria isolation from aspirates or blood cultures performed preoperatively;
• serum C-reactive protein higher than 10 mg/L;
• recurrent implant dislocations;
• prosthetic fracture;
• medical history for septic arthritis, osteomyelitis;
• infections in anatomic areas other than hip;
• antibiotic therapy in the 15 days prior to surgery (with the exception of preoperative antibiotic prophylaxis);
• chronic treatment with immunosuppressive drugs;
• medical contraindications for executing sample collection.