Oral Antibiotics for Prosthetic Joint Infections

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a 7-day course of oral antibiotics can reduce infections and wound complications after hip or knee replacement surgery. The treatment involves either Cephalexin or Doxycycline, chosen based on individual health factors like allergies or kidney function. Participants will receive either additional antibiotics or just standard care, allowing researchers to compare outcomes. Ideal participants are those undergoing elective hip or knee replacement who have conditions like diabetes, are smokers, or have a BMI over 35, which puts them at high risk for infections. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for these treatments?

Research shows that both Cephalexin and Doxycycline are safe and well-tolerated antibiotics for treating infections in artificial joints.

Cephalexin is often used as a pill following certain IV treatments for joint infections. Although not officially approved for this use, it is considered safe and effective due to its widespread application in treating infections.

Doxycycline is also safe for treating infections in artificial joints, particularly those caused by Staphylococcus aureus. Studies have found it effective and generally well-tolerated, meaning it controls infections without major side effects.

Both antibiotics are trusted for their safety in similar medical situations. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using oral antibiotics like Cephalexin and Doxycycline for prosthetic joint infections because they offer a simpler, more convenient treatment option compared to the traditional use of intravenous antibiotics. This approach can potentially reduce hospital stays and healthcare costs, as patients can take these medications at home after surgery. Additionally, selecting antibiotics based on individual factors like allergies, kidney function, and MRSA colonization provides a personalized treatment plan that may improve outcomes and minimize side effects.

What evidence suggests that this trial's treatments could be effective for prosthetic joint infections?

Research has shown that first-generation cephalosporins, such as Cephalexin, used as preventive antibiotics, can significantly reduce the risk of infections around joint implants after surgery. Specifically, patients who received these antibiotics were 39% less likely to develop infections compared to those who received standard care. In this trial, participants in the Additional Antibiotic Group will receive either Cephalexin or Doxycycline based on specific criteria. Doxycycline effectively treats these infections, particularly those caused by bacteria like Staphylococcus aureus. Both antibiotics have shown promise in reducing infections and complications after joint replacement surgeries. ^{4 6 7 8 9}

Who Is on the Research Team?

Nicholas Bedard, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10200839/

Effect of non-cephalosporin antibiotic prophylaxis on the ... Studies have shown an increased risk for periprosthetic joint infection (PJI) when non-cephalosporin antibiotics have been used.

2. arthroplastyjournal.org arthroplastyjournal.org/article/S0883-5403(24)00014-7/pdf

Extended Prophylactic Antibiotics for Primary and Aseptic ... Extended postoperative · prophylactic antibiotics with first-generation cephalosporin do not reduce the · risk of periprosthetic joint infection ...

3. journals.asm.org journals.asm.org/doi/10.1128/aac.00338-25

Advancing the management of prosthetic joint infections Treatment with PLG0206 resulted in complete bacterial eradication in 59% of samples and achieved a mean 4-log10 reduction in bacterial burden ( ...

4. josr-online.biomedcentral.com josr-online.biomedcentral.com/articles/10.1186/s13018-025-06257-2

Periprosthetic joint infection after arthroplasty: advances and ... For aseptic revision TJA, EAP has been shown to significantly reduce infection rates in several studies [95, 96]. A meta-analysis including 18 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883540324000147

Extended Prophylactic Antibiotics for Primary and Aseptic ... Patients treated with EAP were 35% less likely to develop PJI relative to the SoC (P = .0004). When examining primary TJA, patients treated with EAP were 39% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9025623/

Antibiotic Therapy for Prosthetic Joint Infections: An Overview Cefazolin or cloxacillin is the first-line antibiotic in this context. Third-generation cephalosporins are recommended when Gram-negative rods are suspected.

7. academic.oup.com academic.oup.com/cid/article/56/1/e1/415705

Diagnosis and Management of Prosthetic Joint Infection The focus of these guidelines is to provide a consensus statement that addresses the diagnosis and the medical and surgical treatment of infections involving a ...

8. doctorabad.com doctorabad.com/uptodate/d/topic.htm?path=cephalexin-drug-information

Cephalexin: Drug information Prosthetic joint infection (off-label use): Oral: Treatment (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement ...

9. orthobullets.com orthobullets.com/recon/5004/prosthetic-joint-infection

Prosthetic Joint Infection - Recon no method exists to safety remove biofilm and eradication is difficult. prosthetic explant indicated with infection >4 weeks due to biofilm.