Gut Microbiome of Patients Undergoing Antibiotic Therapy for Orthopedic Device-related Infection (IMPAT-ODRI)

Investigation of the Microbiome of Patients Receiving Antibiotic Therapy for Orthopedic Device-related Infection

The microbiome of 80 orthopedic-device related infection (ODRI) patients treated with antibiotics and 10 healthy controls will be investigated. Samples (blood, stool, saliva, skin-swab) are collected 4x within 6 months. Composition and diversity of the microbiome will be assessed by 16sRNA sequencing, skins swabs are screened for rifampicin-resistant staphylococci onto Mannitol-salt-agar plates supplemented with rifampicin, inflammation markers and antibodies in blood and saliva are monitored to track changes in the immune response. For further analysis patients are assigned to one of two groups: 1) antibiotic therapy including rifampicin and 2) non-rifampicin antibiotic therapy.

Study Overview

• Status: Completed
• Conditions: Fractures, Bone; Infection, Bacterial; Bone Infection; Joint Infection
• Intervention / Treatment: Other: no intervention, observational only

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel
  • Zürich, Switzerland, 8008
    • Schulthess Klinik Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The project population will include patients suffering from an ODRI (orthopedic device-related infection). This includes any patient with a bone infection with a current or previous involvement of an implant. The majority of patients are expected to be prosthetic joint infection (PJI) and fracture-related infection (FRI) patients, although also patients with spinal implantation with an infection, or patients who have had an implant removed yet develop an osteomyelitis will also be included.

These patients all have a deep bone implant infection and will receive antibiotic therapy, including at least two weeks IV therapy and at least 4 weeks of oral rifampicin. The investigators expect the distribution of patients getting rifampicin or non-rifampicin to be approximately 50/50 overall and anticipate PJI patients will be older, receive more concomitant medications and have underlying co-morbidities than patients with an FRI.

Description

Inclusion Criteria:

• The patient is planned to undergo revision surgery due to suspected bone or joint infection.
• The patient is at least 18 years old

Exclusion Criteria:

• The patient took antibiotics in the previous six weeks of recruitment (a single dose/"shot" of antibiotics during this period is not considered).
• The patient suffers from gut-associated morbidities such as Morbus Crohn or colitis ulcerosa.
• The patient suffers from psychiatric disorders/cognitive impairment affecting understanding.
• The patient is unable to give consent and follow procedures and/or has insufficient knowledge of the project language.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Antibiotic therapy including rifampicin	Other: no intervention, observational only; no intervention, observational only
Non-rifampicin antibiotic therapy	Other: no intervention, observational only; no intervention, observational only
Control group (healthy volunteers)	Other: no intervention, observational only; no intervention, observational only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the the gut microbiota following two weeks of intravenous antibiotic therapy	The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following two weeks of intravenous (iv) antibiotic treatment will be compared to baseline samples of the patients.	Two weeks
Composition of the gut microbiota following four weeks of oral antibiotic therapy	The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following four weeks of oral antibiotic treatment will be compared to baseline samples of the patients.	Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
Composition of the gut microbiota 24 weeks after antibiotic therapy start	The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition 24 weeks after antibiotic therapy start, including an at least 6-week antibiotic free period, will be compared to baseline samples of the patients.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring Rifampicin resistant S. aureus on the skin following two weeks of iv antibiotic therapy	Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.	Two weeks
Monitoring Rifampicin resistant S. aureus on the skin following four weeks of oral antibiotic therapy	Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.	Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
Monitoring Rifampicin resistant S. aureus on the skin 24 weeks after antibiotic therapy start	Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of systemic Inflammation following two weeks of iv antibiotic therapy	Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.	Two weeks
Level of systemic Inflammation following four weeks of oral antibiotic therapy	Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.	Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
Level of systemic Inflammation 24 weeks after antibiotic therapy start	Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.	24 weeks
Monitoring mucosal immune response following two weeks of iv antibiotic therapy	IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.	Two weeks
Monitoring mucosal immune response following four weeks of oral antibiotic therapy	IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.	Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
Monitoring mucosal immune response 24 weeks after antibiotic therapy start	IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.	24 weeks

Collaborators and Investigators

• Sponsor: AO Research Institute Davos

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2019
• Primary Completion (ACTUAL): June 1, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (ACTUAL): June 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Gut Microbiome; Antibiotic Therapy; Bone Infection; Joint Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Wounds and Injuries; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Fractures, Bone; Bacterial Infections; Prosthesis-Related Infections
• Other Study ID Numbers: Microbiome

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No