Oral Antibiotics for Prosthetic Joint Infections

Recruiting at 3 trial locations

Overseen By Jacob Elkins, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Iowa

Disqualifiers: Clostridium difficile colitis, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

4618 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine the effectiveness of a 7-day course of an oral, prophylactic antibiotic on the incidence of periprosthetic joint infection and wound complications following primary total hip and knee arthroplasty in a high-risk patient population.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug doxycycline for prosthetic joint infections?

A study involving 39 patients with Staphylococcus aureus prosthetic joint infections found that oral doxycycline was effective as a suppressive antibiotic therapy, with 74.4% of patients remaining event-free, suggesting it is a reasonable option for this condition. ^{1 2 3 4 5}

Is doxycycline generally safe for humans?

Doxycycline is generally well tolerated in humans, with common side effects including stomach upset, nausea, and diarrhea. New formulations, like enteric-coated doxycycline, have been developed to reduce these gastrointestinal side effects. ^{2 6 7 8 9}

How is the drug treatment with Cephalexin and Doxycycline unique for prosthetic joint infections?

The combination of Cephalexin and Doxycycline for treating prosthetic joint infections is unique because it offers an oral antibiotic option that can be used for chronic suppression to prevent infection recurrence, especially when other bacteria are resistant to common treatments like doxycycline alone. This approach provides a potentially effective and tolerable alternative for managing these infections without the need for intravenous antibiotics. ^{1 4 10 11 12}

Research Team

Nicholas Bedard, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults needing a first-time hip or knee replacement who are at high risk of infection due to obesity, diabetes, smoking, kidney disease, autoimmune conditions, or nasal colonization with Staphylococcus bacteria. It's not for those allergic to the study antibiotics, unable to take oral meds, pregnant women, or patients planning other joint replacements soon.

Inclusion Criteria

I am scheduled for a first-time hip or knee replacement surgery.

I am at high risk for joint infections due to one or more health issues.

Exclusion Criteria

I am having or have had a hip or knee replacement redone.

I am allergic to certain antibiotics listed in the treatment plan.

Pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Participants undergo primary hip or knee arthroplasty and receive standard perioperative antibiotics

1 week

Post-Surgery Treatment

Participants receive a 7-day course of an oral, prophylactic antibiotic or no additional antibiotic

1 week

Follow-up

Participants are monitored for surgical wound complications and periprosthetic joint infections

1 year

Treatment Details

Interventions

• Cephalexin Oral Tablet
• Doxycycline Hyclate

Trial Overview The trial tests if taking an antibiotic (Cephalexin, Doxycycline or Cefadroxil) for 7 days can prevent infections and wound issues after hip or knee replacement surgery in high-risk patients. Participants will receive one of these antibiotics as a preventative measure.

Participant Groups

Group I: Additional Antibiotic Group Active Control 3 Interventions

Patients will receive an oral antibiotic to be started after completion of standard perioperative antibiotics following primary hip or knee arthroplasty. Oral antibiotic will either be a first-generation cephalosporin (Cefadroxil or Cephalexin) or Doxycycline based upon patient allergies, kidney function and result of nasal colonization testing for MRSA.

Group II: Control Group - No Additional Antibiotic Active Control 1 Intervention

Patients will receive standard perioperative antibiotics following primary hip or knee arthroplasty and no additional antibiotics.

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a study involving 98 healthy subjects, Doryx (enteric-coated doxycycline) was found to cause significantly fewer gastrointestinal side effects, such as nausea and abdominal discomfort, compared to Vibramycin (doxycycline powder).

While Doryx did lead to some reports of nausea compared to placebo, it overall had a better safety profile regarding gastrointestinal symptoms than Vibramycin, making it a preferable option for patients concerned about these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. Berger, RS.[2019]

In a study of 78 patients with periprosthetic joint infections (PJIs), oral cyclines (doxycycline and minocycline) were found to have acceptable tolerability and effectiveness as suppressive antibiotic therapy, with only 18% reporting adverse events.

After an average follow-up of about 3 years, 28.2% of patients experienced treatment failure, indicating that while cyclines can be effective, there is a risk of developing antibiotic resistance in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. Pradier, M., Robineau, O., Boucher, A., et al.[2018]

In a study of 39 patients with Staphylococcus aureus periprosthetic joint infections, oral doxycycline as suppressive antibiotic therapy showed good tolerability, with only 15.4% experiencing adverse events, and 74.4% remaining free of complications after treatment.

Doxycycline demonstrated effectiveness in managing these infections, with 25.6% of patients experiencing treatment failure, primarily due to relapses related to doxycycline-susceptible pathogens, indicating it can be a viable option for patients at high risk of infection failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. Pradier, M., Nguyen, S., Robineau, O., et al.[2018]

A daily maintenance dose of 100 mg doxycycline was found to be effective and well tolerated in treating bacterial infections in patients with chronic obstructive pulmonary disease (COPD).

The treatment successfully eliminated bacteria such as H. influenzae and pneumococci, indicating that higher doses are not needed for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. Eicke, R., Genz, U., Bartmann, K., et al.[2020]

In a study involving 111 healthy volunteers, enteric-coated doxycycline hyclate pellets in capsules were found to cause significantly fewer gastrointestinal adverse reactions compared to doxycycline monohydrate tablets, with only 43% of participants reporting side effects versus 66% for monohydrate.

The new formulation demonstrated improved tolerability, particularly reducing incidents of abdominal pain, nausea, and vomiting, making it a safer option for patients requiring doxycycline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. Järvinen, A., Nykänen, S., Paasiniemi, L., et al.[2018]

Doxycycline is effective against a wide range of bacterial infections and is particularly notable for its safety profile, as it does not require dosage adjustments in patients with renal failure.

It is well tolerated with common side effects like stomach upset and nausea, but new formulations are available to minimize these issues; however, it is contraindicated in children and pregnant or breastfeeding women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Doxycycline]. Aupee, O., Almeras, D., Le Garlantezec, P., et al.[2013]

Doxycycline is an effective antibiotic for treating various infections, particularly respiratory tract diseases like pneumonia, as demonstrated in a study involving 49 patients.

The drug shows good safety and compatibility, especially in children, and achieves effective serum levels when administered at a dose of 4 mg/kg in two injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. Weingärtner, L., Straube, D., Baum, W., et al.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Retention of Minocycline Susceptibility When Gram-Positive Periprosthetic Joint Infection Isolates Are Non-Susceptible to Doxycycline. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Can Serum Drops Containing Doxycycline Provide a Supplemental Anti-Bacterial Effect in the Treatment of Bacterial Keratitis? [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. [2018]

8. France pubmed.ncbi.nlm.nih.gov

[Doxycycline]. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Total joint replacement: a consideration for antimicrobial prophylaxis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Treatment of acute post-surgical infection of joint arthroplasty. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Impact of rifampicin dose in bone and joint prosthetic device infections due to Staphylococcus spp: a retrospective single-center study in France. [2023]