Oral Antibiotics for Bacterial Blood Infection

(GOAT Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen by Pranita D Tamma, MD, MHS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Polymicrobial infection, CNS infection, others

No Placebo Group

Approved in 2 Jurisdictions

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Rochester, MN

Denver Health Hospital Authority Denver, CO

Rutgers-RWJ University Hospital New Brunswick, NJ

Duke University Durham, NC

More Trial Locations

Who Is Running the Clinical Trial?

Johns Hopkins University Lead Sponsor

Patient-Centered Outcomes Research Institute Collaborator

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] In this study, we evaluated the clinical outcomes associated with the use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared with the less-bioavailable oral antibiotics (β-lactams) in gram-negative bloodstream infections (BSIs).

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

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. [2022] There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for

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

Susceptibility of blood isolates to various antibiotics, in particular to cephalosporins. [2019] Of 760 bacterial pathogens isolated from blood cultures of acutely ill patients in a general hospital in Hong Kong for 1 year, 69.9% of the isolates were Gram-negative aerobes mainly Escherichia coli and Klebsiella pneumoniae, 22.0% were Gram-positive aerobes mainly Staphylococcus aureus and enterococci and 8.1% were anaerobes mainly Bacteroides spp. The susceptibility of the aerobic isolates to various antibiotics was tested. Ampicillin was found to be active mainly against the enterococci and some other Gram-positive organisms while most isolates of Staph. aureus and the Gram-negative bacteria were resistant. In contrast, cephalothin was found only slightly less active than the second generation cephalosporins against Gram-negative blood isolates but considerably more active against Staph. aureus and other Gram-positive isolates. The three aminoglycosides tested, i.e., gentamicin, tobramycin and amikacin, showed similar good activity against E. coli, K. pneumoniae and Proteus mirabilis, but amikacin had the broadest spectrum of activity in inhibiting most of the other Gram-negative isolates as well as isolates of Staph. aureus. The third generation cephalosporins, cefotaxime, cefoperazone, latamoxef (moxalactam), ceftriaxone and ceftazidime, all had a high activity against the Gram-negative but a reduced activity against the Gram-positive bacteria. Ceftazidime had the broadest spectrum of activity in inhibiting all the Gram-negative isolates including Pseudomonas aeruginosa, while cefotaxime showed the best overall activity against both Gram-positive and Gram-negative blood isolates.

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] Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections.

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

Antibiotic therapy for gram-negative bacteremia. [2005] Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

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] Antimicrobial-resistant bacterial infections, particularly those caused by Gram-negative bacteria, are major public health threats globally. Since 2015, several antibiotics with activity against highly antimicrobial-resistant Gram-negative bacteria have been approved, which offer alternatives emerging to previous frontline agents such as polymyxins and aminoglycosides. Despite data that new drugs are more effective and better tolerated than older agents against at least some highly antimicrobial-resistant Gram-negative bacterial infections, clinicians remain uncertain about how best to incorporate them into clinical practice. In this article, we discuss the management of highly resistant Gram-negative bacterial infections in the era of new antibiotics, with particular attention to those caused by AmpC- and extended-spectrum β-lactamase-producing Enterobacterales (which manifest phenotypically as 3rd generation cephalosporin resistance), carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant acinetobacter baumannii, and Stenotrophomonas maltophilia.

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] Bloodstream infection remains a major cause of morbidity and mortality in patients undergoing treatment for cancer. Severe infections due to Gram-negative bacilli & staphylococci are common in cancer patients. Altered gut flora because of frequent antibiotic administration and damage of epithelial surfaces contribute to the development of infection. To access the use of new potent antibiotics against bloodstream infection in cancer patients and to determine the cross resistance of Gram-negative bacterial strains.

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

Spectrum and treatment of bacterial infections in cancer patients with granulocytopenia. [2019] Bacterial infections remain a frequent cause of morbidity and mortality in cancer patients with granulocytopenia. In recent years the proportion of patients with gram-positive infections, caused mainly by coagulase-negative staphylococci and viridans streptococci, has increased markedly in many institutions. The precise reasons for this recent change in the epidemiology of infection in cancer patients are as yet not fully ascertained. Although less prevalent, gram-negative infections are still the major threat, since they are associated with higher mortality. What constitutes the optimal empirical antibiotic therapy remains a controversial issue. One should however recognize that the results of one particular study may not be relevant to other institutions where the predominant pathogens and the pattern of antibiotic resistance may be different. In addition, the results of studies using various antibiotic regimens should be compared with caution. However, with these limitations in mind, the results of the most recently published studies support the following recommendations: in patients with nonmicrobiologically documented infections, monotherapy with a third-generation cephalosporin or a carbapenem is a safe alternative to combination therapy. For gram-negative bacteremia, combined therapy with an extended-spectrum beta-lactam antibiotic and an aminoglycoside appears preferable. For gram-positive infections, a specific anti-gram-positive antibiotic is not needed in every patient and can safely be added upon identification of the pathogen in those patients not responding to empirical therapy.

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] Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions.

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] Treatment of bacteraemia with oral antibiotics has the potential to reduce hospital length of stay, treatment costs and line-related complications. To date, small trials have supported the use of specific classes of antibiotics, primarily fluoroquinolones (FQs), in the treatment of Gram-negative bloodstream infections (GNBSIs). Currently, limited data exist evaluating treatment with β-lactams (BLs) or trimethoprim/sulfamethoxazole (SXT). The purpose of this study was to compare treatment of GNBSIs across three different oral antibiotic classes.