Topical Antibiotics for Surgical Site Infection

Recruiting at 46 trial locations

Overseen By Suna Chung, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Major Extremity Trauma Research Consortium

Must not be taking: Vancomycin, Aminoglycosides

Disqualifiers: Infection, Myonecrosis, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-surgery

1900 Participants Needed

Trial Summary

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 Tobramycin for surgical site infections?

Research shows that Tobramycin is effective against certain bacteria, including Pseudomonas and Staphylococcus aureus, which are common in infections. It has been found to be more effective than gentamicin in treating bacterial infections of the eye and is also effective in treating surgical infections, particularly those caused by gram-negative bacteria. ^{1 2 3 4 5}

Is topical tobramycin safe for use in humans?

Topical tobramycin is generally safe for use in humans, with studies showing it has a lower frequency of adverse reactions compared to gentamicin. No liver or bone marrow toxicity was observed, and while there were some cases of kidney and ear toxicity, these were mostly linked to other factors. ^{1 3 5 6 7}

What makes the drug Tobramycin unique for treating surgical site infections?

Tobramycin is unique because it is an aminoglycoside antibiotic that is particularly effective against certain bacteria like Pseudomonas and Staphylococcus aureus, which are common in infections. It has been shown to be more effective than gentamicin, another similar antibiotic, and has a lower frequency of adverse reactions when used topically. ^{1 2 3 7 8}

What is the purpose of this trial?

The overall objective is to compare the effect of Vancomycin and Tobramycin powder combined (treatment) to Vancomycin powder (control) in the reduction of post-fixation infections of tibial plateau and tibial pilon fractures at high risk of infection (collectively considered the "study injuries").

Research Team

Robert O'Toole, MD

Principal Investigator

University of Maryland, Department of Orthopaedic Trauma

Renan C Castillo, PhD

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Anthony R Carlini, MS

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Eligibility Criteria

Adults aged 18-80 with high-risk tibial fractures initially treated with external fixation, who are now receiving plate and screw fixation. Ideal candidates have no severe allergies to Vancomycin or Tobramycin, are not pregnant, and can commit to follow-up appointments.

Inclusion Criteria

I have an open fracture type I, II, or IIIA.

I was first treated with a brace or cast and had definitive treatment after 3 days once swelling went down.

My leg fracture was treated with surgery using plates and screws, and it's at a high risk of infection.

Exclusion Criteria

Study injury is already infected at time of study enrollment.

Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).

Currently pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Vancomycin powder or a combination of Vancomycin and Tobramycin powders in their wound bed immediately before wound closure

Immediate post-surgery

Follow-up

Participants are monitored for deep surgical site infections and antibiotic resistance

26 weeks

Extended Follow-up

Participants are monitored for additional sensitivity analyses and antibiotic resistance

52 weeks

Treatment Details

Interventions

• Tobramycin
• Vancomycin

Trial Overview The TOBRA study is testing if a combination of Vancomycin and Tobramycin powders reduces infection rates post-surgery better than just Vancomycin powder in patients with certain high-risk leg fractures.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed immediately before wound closure.

Group II: Control Active Control 1 Intervention

Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed immediately before wound closure.

Tobramycin is already approved in United States, European Union for the following indications:

Approved in United States as Tobramycin for:

• Cystic fibrosis-associated bacterial infections
• Lower respiratory tract infections
• Urinary tract infections
• Eye infections
• Skin infections
• Bone infections
• Skin structure infections

Approved in European Union as Tobramycin for:

• Cystic fibrosis-associated bacterial infections
• Lower respiratory tract infections
• Urinary tract infections
• Eye infections
• Skin infections
• Bone infections
• Skin structure infections

Who Is Running the Clinical Trial?

Major Extremity Trauma Research Consortium

Lead Sponsor

Trials

32

Recruited

27,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Tobramycin is highly effective against certain strains of Pseudomonas and Staphylococcus aureus, but many strains of Serratia and Streptococcus pneumoniae show resistance to it at achievable concentrations in humans.

The effectiveness of tobramycin can be influenced by the growth medium and the presence of calcium and magnesium ions, which inhibit its bactericidal action, while it works synergistically with carbenicillin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro studies of tobramycin, an aminoglycoside antibiotic. Dienstag, J., Neu, HC.[2021]

Tobramycin is an aminoglycoside antibiotic that is more effective against Pseudomonas aeruginosa than gentamicin and may have a lower risk of causing hearing loss (ototoxicity), making it a promising option for treating certain infections in pediatric patients.

It is crucial to confirm in vitro susceptibility to tobramycin before use, as resistance can occur, and careful monitoring of serum concentrations is necessary to ensure safe and effective dosing, especially in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary: An appraisal of tobramycin usage in pediatrics. McCracken, GH., Nelson, JD.[2019]

In a study of 511 patients with bacterial eye infections, tobramycin was found to be significantly more effective than gentamicin sulfate in resolving symptoms and signs of infection.

Tobramycin also demonstrated greater antibacterial efficacy against common pathogens like Staphylococcus aureus and had a lower frequency of adverse reactions compared to gentamicin, likely due to differences in preservatives used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical tobramycin and gentamicin sulfate in the treatment of ocular infections: multicenter study. Cagle, G., Davis, S., Rosenthal, A., et al.[2014]

In a study of 26 gentamicin-resistant Pseudomonas aeruginosa isolates from hospitalized children, tobramycin showed the highest effectiveness, with 23% of isolates inhibited by achievable concentrations, while gentamicin and netilmicin were ineffective against all isolates.

Combining carbenicillin with tobramycin, sisomicin, or amikacin was found to be synergistic for 92% of the strains, suggesting that this combination could be a safe and effective initial treatment for infections caused by gentamicin-resistant Pseudomonas pending further susceptibility testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of newer aminoglycosides and carbenicillin, alone and in combination, against gentamicin-resistant Pseudomonas aeruginosa. Marks, MI., Hammerberg, S., Greenstone, G., et al.[2021]

In a study of 116 septic surgical patients, tobramycin was found to be as effective as gentamicin in treating infections, with a higher likelihood of susceptibility to gram-negative bacteria.

While there were some cases of nephrotoxicity and ototoxicity, these were mostly linked to other factors like prior renal damage rather than tobramycin itself, indicating a relatively safe profile for this new antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of surgical infections with tobramcin. Stone, HH., Kolb, LD., Geheber, CE., et al.[2019]

Tobramycin solution for inhalation (TOBI) is the only FDA-approved inhaled antibiotic for maintenance therapy in cystic fibrosis patients aged 6 and older who are colonized with Pseudomonas aeruginosa, specifically for those with moderate lung function (25%-75% FEV1).

The approval of TOBI does not extend to treating acute pulmonary exacerbations in cystic fibrosis or for use in patients without cystic fibrosis, highlighting its specific therapeutic role and the lack of other inhaled antibiotics approved for similar use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical report: precautions regarding the use of aerosolized antibiotics. Committee on Infectious Diseases and Committee on Drugs. Prober, CG., Walson, PD., Jones, J.[2019]

Tobramycin was administered to 28 patients with gram-negative infections, showing effective serum levels and resulting in 18 cures, indicating its efficacy against bacteria like Pseudomonas aeruginosa and Klebsiella pneumoniae.

The treatment demonstrated minimal hepatic and renal toxicity, suggesting that tobramycin is a safe option for patients, even those with renal insufficiency when dosages were adjusted accordingly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with tobramycin in the treatment of infections due to gram-negative bacilli. Carmalt, ED., Cortez, LM., Rosenblatt, JE.[2019]

Subconjunctival injection of tobramycin sulphate resulted in therapeutically effective concentrations in the aqueous humour (mean: 18.9 microgram/ml), indicating its potential effectiveness for treating ocular infections.

In contrast, intramuscular injections of tobramycin produced insignificant levels in the aqueous humour, suggesting that this route is not effective for ocular treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penetration of tobramycin sulphate into the human eye. Petounis, A., Papapanos, G., Karageorgiou-Makromihelaki, C.[2019]

References

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

In vitro studies of tobramycin, an aminoglycoside antibiotic. [2021]

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

Commentary: An appraisal of tobramycin usage in pediatrics. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Topical tobramycin and gentamicin sulfate in the treatment of ocular infections: multicenter study. [2014]

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

Activity of newer aminoglycosides and carbenicillin, alone and in combination, against gentamicin-resistant Pseudomonas aeruginosa. [2021]

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

Treatment of surgical infections with tobramcin. [2019]

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

Technical report: precautions regarding the use of aerosolized antibiotics. Committee on Infectious Diseases and Committee on Drugs. [2019]

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

Clinical experience with tobramycin in the treatment of infections due to gram-negative bacilli. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Penetration of tobramycin sulphate into the human eye. [2019]