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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if switching to oral antibiotics early can treat Gram-negative bloodstream infections as effectively and more safely than continuing with IV antibiotics. Researchers will randomly assign participants to receive either oral or IV antibiotics for their treatment. Suitable candidates are adults currently hospitalized with a confirmed Gram-negative bacterial infection in their blood who can manage oral antibiotics. The goal is to discover if oral antibiotics provide a simpler and potentially safer treatment option. As an unphased trial, this study allows patients to contribute to important research that could simplify and enhance future treatment options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking oral antibiotics for bacterial blood infections can be safe and effective. One study found that starting treatment early with oral antibiotics for certain low-risk infections was both feasible and safe, with patients experiencing positive outcomes without major issues.

Another study demonstrated that high-dose oral antibiotics were as effective as other treatments, such as fluoroquinolones or trimethoprim-sulfamethoxazole, for urinary tract infections. Most participants tolerated these oral antibiotics without serious side effects.

Switching from intravenous (IV) antibiotics to oral antibiotics after a few days can also be effective. This change may reduce complications related to IV lines, such as infections at the insertion site.

Overall, evidence suggests that oral antibiotics are well-tolerated and can be a viable option for treating bacterial blood infections. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using oral antibiotics for bacterial blood infections because they promise greater convenience and comfort compared to the standard intravenous (IV) options. Oral antibiotics can be taken at home, potentially reducing the need for hospital stays and IV lines, which can be cumbersome and uncomfortable. This approach could also lead to cost savings and easier access to treatment. While IV antibiotics are effective, the possibility of achieving similar outcomes with oral medications is an exciting advancement that could simplify treatment for many patients.

What evidence suggests that oral antibiotics might be an effective treatment for Gram-negative bloodstream infections?

Research has shown that taking antibiotics orally can be as effective as receiving them through an IV for certain bloodstream infections. In this trial, participants will receive either oral antibiotics or intravenous (IV) antibiotics. Studies have found that high-dose oral antibiotics work well for infections originating in the urinary tract, offering similar safety and effectiveness as other treatments. One study found that switching to oral antibiotics can shorten hospital stays and reduce treatment costs. Real-world evidence suggests that oral antibiotics are as effective as IV antibiotics and come with fewer complications related to IV lines. Overall, oral antibiotics present a promising option for effectively treating these infections. ^{2 3 4 6 7}

Who Is on the Research Team?

Pranita D Tamma, MD, MHS

Principal Investigator

Johns Hopkins University

Sara E Cosgrove, MD, MS

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 currently in the hospital.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2404991

Antibiotic Treatment for 7 versus 14 Days in Patients with ... By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10523554/

Outcomes of high-dose oral beta-lactam definitive therapy ... High-dose oral beta-lactams were as safe and effective as oral FQ or TMP/SMX for the treatment of bacteremia from a urinary source. Most patients received 8–10 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213716519301924

Oral antibiotics for the treatment of Gram-negative ... Treatment of bacteraemia with oral antibiotics has the potential to reduce hospital length of stay, treatment costs and line-related complications.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831846

Seven vs Fourteen Days of Antibiotics for Gram-Negative ... These findings suggest that most Gram-negative bloodstream infections can be treated with 7 days of antibiotics unless there is a concern for inadequate source ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38665174/

Real-World Effectiveness of Intravenous and Oral Antibiotic ... These real-world data suggest that oral stepdown therapy with FQs or TMP-SMX have similar effectiveness as IVBLs. HBBLs were associated with higher recurrence ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10648851/

Safety of early oral ambulatory treatment of adult patients ... In conclusion, the early oral, ambulatory treatment of low-risk bacteremic infections seems feasible and safe. These results provide a proof of ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814214

Early Switch From IV to Oral Antibiotics for Uncomplicated ... The results suggest that transition to oral antibiotics within 4 days after initial blood culture may be an effective alternative to prolonged IV antibiotic ...