Oral Antibiotics for Bacterial Blood Infection

(GOAT Trial)

Recruiting at 10 trial locations

Overseen By Sara E Cosgrove, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Polymicrobial infection, CNS infection, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 days for initial IV treatment, followed by oral antibiotics

1204 Participants Needed

Trial Summary

What is the purpose of this trial?

The Gram-negative bloodstream infection Oral Antibiotic Therapy trial (The GOAT Trial) is a multi-center, randomized clinical trial that hypothesizes that early transition to oral antibiotic therapy for the treatment of Gram-Negative BloodStream Infection (GN-BSI) is as effective but safer than remaining on intravenous (IV) antibiotic therapy for the duration of treatment.

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 for treating bacterial blood infections?

Research shows that early and appropriate antibiotic treatment significantly improves outcomes for patients with gram-negative bloodstream infections. Studies have found that certain oral antibiotics, like fluoroquinolones, are highly effective due to their good absorption in the body, which can help treat these infections effectively. ^{1 2 3 4 5}

Is it safe to use oral antibiotics for bacterial blood infections?

Research suggests that newer oral antibiotics for Gram-negative bacterial infections are generally better tolerated than older ones, indicating they are safe for use in humans. ^{1 2 6 7 8}

How do oral antibiotics differ from other treatments for bacterial blood infections?

Oral antibiotics for bacterial blood infections are unique because they allow patients to switch from intravenous (IV) to oral medication, potentially reducing hospital stays and treatment costs. This approach is different from traditional treatments that often rely on prolonged IV antibiotic use. ^{1 2 5 9 10}

Research Team

Pranita D Tamma, MD, MHS

Principal Investigator

Johns Hopkins University

Sara E Cosgrove, MD, MS

Principal Investigator

Johns Hopkins University

Eligibility Criteria

Adults over 18 with a Gram-negative bacterial infection in their bloodstream, who can give informed consent and are willing to follow the study procedures. Participants must be hospitalized and able to complete a quality of life interview.

Inclusion Criteria

Willingness to adhere to assigned study arm

Identification of at least one Gram-negative organism in a blood culture

I am 18 years old or older.

Exclusion Criteria

I am allergic or cannot take certain antibiotics by mouth or IV.

I am currently receiving hospice care.

I do not have an infection in my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either IV antibiotics or transition to oral antibiotics for the treatment of Gram-Negative Bloodstream Infection

Up to 5 days for initial IV treatment, followed by oral antibiotics

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of clinical response and adverse events

30 days

Treatment Details

Interventions

• Oral Antibiotics

Trial Overview The GOAT Trial is testing whether taking oral antibiotics at home is as effective and safer than staying on intravenous antibiotics for treating Gram-Negative Bloodstream Infections.

Participant Groups

Group I: Intravenous Antibiotics Active Control 1 Intervention

IV antibiotics from the time of randomization to the completion of antibiotic treatment. Includes antibiotics such as ceftriaxone, cefepime, piperacillin-tazobactam, and meropenem.

Group II: Oral Antibiotics Active Control 1 Intervention

Oral antibiotics from the time of randomization to the completion of antibiotic treatment, Includes antibiotics such as amoxicillin, cephalexin, ciprofloxacin, and trimethoprim-sulfamethoxazole.

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

Approved in United States as Oral Antibiotics for GN-BSI for:

• Gram-Negative Bloodstream Infections

Approved in European Union as Oral Antibiotics for GN-BSI for:

• Gram-Negative Bloodstream Infections

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Findings from Research

In a study of 2012 hospitalized older adults with gram-negative bloodstream infections, those treated with highly bioavailable oral antibiotics (like fluoroquinolones and trimethoprim-sulfamethoxazole) had significantly better clinical outcomes compared to those on less bioavailable antibiotics (β-lactams).

Patients receiving highly bioavailable antibiotics had a lower rate of composite outcomes, including 90-day all-cause mortality and recurrent infections, with a notable reduction in recurrent bloodstream infections (5.4% vs. 9.4%), indicating these antibiotics may be more effective in preventing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis. Mponponsuo, K., Brown, KA., Fridman, DJ., et al.[2023]

In a study of 362 patients with Gram-negative bloodstream infections, those treated with oral antibiotics that had high bioavailability (≥95%) experienced a significantly lower treatment failure rate of 2%, compared to 12% and 14% for those on moderate (75-94%) and low (<75%) bioavailability antibiotics, respectively.

The risk of treatment failure increased notably with lower bioavailability, with moderate and low bioavailability antibiotics showing adjusted hazard ratios of 5.9 and 7.7, indicating a much higher likelihood of treatment failure compared to high bioavailability options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. Kutob, LF., Justo, JA., Bookstaver, PB., et al.[2022]

In a study of 760 bacterial pathogens from blood cultures in Hong Kong, 69.9% were Gram-negative bacteria, primarily E. coli and K. pneumoniae, indicating a significant prevalence of these pathogens in acutely ill patients.

Antibiotic susceptibility testing revealed that while ampicillin was effective mainly against enterococci, cephalothin and third-generation cephalosporins like cefotaxime showed high activity against Gram-negative bacteria, with cefotaxime demonstrating the best overall effectiveness against both Gram-positive and Gram-negative isolates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Susceptibility of blood isolates to various antibiotics, in particular to cephalosporins. Ling, J., Chau, PY., Leung, YK., et al.[2019]

In a study of 1832 hospitalized patients with Gram-negative bloodstream infections, prior microbiologic results were found to be highly predictive of current antibiotic resistance, with a specificity of 0.92, indicating that knowing a patient's previous infections can guide more effective treatment decisions.

Identifying a recent resistant Gram-negative organism can help avoid ineffective antibiotics in about 25% of patients, potentially changing therapy for one in five of those cases, thus improving patient outcomes in managing bloodstream infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study. MacFadden, DR., Coburn, B., Shah, N., et al.[2018]

Early and appropriate antibiotic treatment for gram-negative bacteremia significantly improves patient outcomes and reduces the risk of septic shock, highlighting the importance of timely intervention.

Monitoring serum antibiotic levels in critically ill patients is crucial, as standard doses may not achieve therapeutic levels, leading to potential relapses or breakthrough infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic therapy for gram-negative bacteremia. Calandra, T., Cometta, A.[2005]

New antibiotics approved since 2015 show improved efficacy and tolerability against highly antimicrobial-resistant Gram-negative bacterial infections compared to older treatments like polymyxins and aminoglycosides.

Despite the availability of these new antibiotics, clinicians are still uncertain about how to effectively integrate them into treatment plans for infections caused by resistant bacteria such as carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Highly Resistant Gram-Negative Infections in the Intensive Care Unit in the Era of Novel Antibiotics. Clancy, CJ., Nguyen, MH.[2022]

In a study of 60 Gram-negative bacterial blood cultures from cancer patients, Pseudomonas aeruginosa was the most frequently isolated pathogen, showing high resistance rates to several antibiotics, including 60% to cefepime and 80% to ciprofloxacin.

Meropenem emerged as the most effective antibiotic against Gram-negative bacteria, suggesting it should be prioritized for treating severe infections in high-risk cancer patients due to the observed high levels of drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and anti-microbial susceptibility of gram-negative bacteria isolated from bloodstream infections of cancer patients on chemotherapy in Pakistan. Saghir, S., Faiz, M., Saleem, M., et al.[2022]

In cancer patients with granulocytopenia, there has been a notable increase in gram-positive infections, particularly from coagulase-negative staphylococci and viridans streptococci, although gram-negative infections still pose a higher mortality risk.

For treating infections in these patients, recent studies suggest that using a third-generation cephalosporin or a carbapenem as monotherapy is a safe option, while combined therapy with an extended-spectrum beta-lactam and an aminoglycoside is recommended for gram-negative bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spectrum and treatment of bacterial infections in cancer patients with granulocytopenia. Calandra, T.[2019]

A panel of 13 infectious diseases specialists developed a consensus definition for uncomplicated gram-negative bloodstream infections, emphasizing factors like host immune status and response to therapy in their assessment.

For patients classified as having uncomplicated infections, the panel recommended a treatment duration of approximately 7 days, transitioning to oral antibiotics, and not performing repeat blood cultures, providing a practical management approach in the absence of formal guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. Heil, EL., Bork, JT., Abbo, LM., et al.[2022]

In a study of 204 hospitalized patients with Gram-negative bloodstream infections (GNBSIs), transitioning from intravenous to oral antibiotics showed a low treatment failure rate of 7.4%, indicating that oral therapy can be a safe option for completing treatment.

No significant differences in treatment failure rates were found among the three oral antibiotic classes (fluoroquinolones, β-lactams, and trimethoprim/sulfamethoxazole), suggesting that as fluoroquinolone resistance rises, alternative oral antibiotics may be equally effective for GNBSI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antibiotics for the treatment of Gram-negative bloodstream infections: A retrospective comparison of three antibiotic classes. Nisly, SA., McClain, DL., Fillius, AG., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. [2022]

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

Susceptibility of blood isolates to various antibiotics, in particular to cephalosporins. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study. [2018]

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

Antibiotic therapy for gram-negative bacteremia. [2005]

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

Management of Highly Resistant Gram-Negative Infections in the Intensive Care Unit in the Era of Novel Antibiotics. [2022]

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

Characterization and anti-microbial susceptibility of gram-negative bacteria isolated from bloodstream infections of cancer patients on chemotherapy in Pakistan. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Spectrum and treatment of bacterial infections in cancer patients with granulocytopenia. [2019]

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

Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Oral antibiotics for the treatment of Gram-negative bloodstream infections: A retrospective comparison of three antibiotic classes. [2021]