Short Antibiotic Treatment for Febrile Neutropenia

Recruiting at 3 trial locations

Overseen By Roni Bitterman, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Antibiotics

Disqualifiers: Septic shock, Solid malignancies, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Infections are a common complication in patients with cancer. They are a significant cause of complications and death in this population. Patients with cancer and low neutrophil counts due to chemotherapy or disease often have a fever and receive antibiotic treatment. The optimal duration of this treatment is largely unknown. Late, there have been some data suggesting the safety of early discontinuation of antibiotics, though most centers still give more prolonged antibiotic therapies in this situation. The unnecessary prolonged antibiotic use may increase infections with multi-drug-resistant bacteria, which carry a high death rate. Also, an increase in infections caused by Clostridioides difficile and an increase in fungal infections can happen. However, some are concerned that stopping antibiotics while the neutrophil count is still low will result in life-threatening infections. Our study aims to test whether shorter antibiotic treatment in these situations is as safe as more prolonged treatment, resulting in better antibiotic prescription practices in this population.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug for febrile neutropenia?

Research shows that starting treatment quickly with broad-spectrum antibiotics (which target a wide range of bacteria) in patients with febrile neutropenia can lower the risk of early death and complications. This suggests that using antibiotics like Tazocin or Zosyn, which are broad-spectrum, could be effective in managing this condition. ^{1 2 3 4 5}

Is short antibiotic treatment for febrile neutropenia safe for humans?

The research does not provide specific safety data for short antibiotic treatment in febrile neutropenia, but it mentions that prompt antibiotic treatment is standard care and reduces infection-related deaths in these patients. ^{1 5 6 7 8}

How is the short antibiotic treatment for febrile neutropenia different from standard treatment?

The short antibiotic treatment for febrile neutropenia is unique because it focuses on reducing the length of antibiotic use, allowing for early transition to outpatient care, unlike the traditional approach which involves prolonged hospitalization with multi-agent antibiotics. ^{1 9 10 11 12}

Research Team

Shahid Husain, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 with acute leukemia or undergoing stem cell transplant, who have low neutrophil counts due to treatment and develop a fever without any documented infection. They must have had negative blood cultures after antibiotics for at least 72 hours.

Inclusion Criteria

I am 18 years old or older.

I am receiving treatment for acute leukemia, including chemotherapy or a stem cell transplant.

I have had a fever with very low white blood cells as per IDSA guidelines.

Exclusion Criteria

Concurrent participation in another interventional trial

I've been on antibiotics for over a week for a fever due to low white blood cells.

I have an infection that has been confirmed by a doctor or lab tests, but not a fungal infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either early discontinuation or prolonged antibiotic treatment based on randomization

30 days

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of antibiotic resistance and adverse events

30 days

Extension

Long-term monitoring for recruitment rate and adherence to intervention

Approximately 2 years

Treatment Details

Interventions

• Early Discontinuation of Antibiotics
• Standard of Care

Trial Overview The study compares the safety of stopping antibiotics early versus the standard longer treatment in cancer patients with febrile neutropenia. It aims to determine if shorter treatments can prevent complications from drug-resistant bacteria and other infections.

Participant Groups

Group I: Short treatment Experimental Treatment 1 Intervention

Antibiotic treatment will be stopped at the time of allocation to the intervention group

Group II: Prolonged treatment Active Control 1 Intervention

Antibiotic treatment will be continued until the resolution of neutropenia (ANC \> 0.5x109/L)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study of 129 pediatric cancer patients with febrile neutropenia, a once-daily antibiotic regimen of ceftriaxone plus amikacin allowed for a significantly shorter hospital stay (median 5 days) compared to imipenem monotherapy (median 9 days), indicating improved hospital utilization.

The once-daily regimen was safe, with no adverse events reported in 84% of patients treated as outpatients, and it also resulted in lower treatment costs, making it a beneficial alternative for managing febrile neutropenia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study. Ahmed, N., El-Mahallawy, HA., Ahmed, IA., et al.[2013]

Among 2131 adult patients receiving myelosuppressive chemotherapy, 16.8% experienced febrile neutropenia, with the highest risk occurring during the first cycle of treatment (8.1%).

Most cases (83.2%) required inpatient treatment, leading to an average hospital stay of 8.4 days and a mortality rate of 8.1%, highlighting the serious consequences of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, treatment, and consequences of chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings. Weycker, D., Barron, R., Kartashov, A., et al.[2022]

In a study of 40 patients with febrile neutropenia after chemotherapy for haematologic malignancies, adherence to established antibiotic guidelines was reasonable, with valid clinical reasons for non-compliance in all cases.

Only 31% of episodes started with the recommended first-line antibiotic (cefepime), and while there were 3 deaths, none were linked to adherence issues, suggesting that the guidelines may need simplification to improve compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of antibiotics in a haematology ward--an audit. Wong, GC., Tan, BH.[2020]

Prompt initiation of broad-spectrum antibiotic therapy for cancer patients experiencing febrile neutropenia significantly reduces early death and morbidity rates, highlighting the importance of timely treatment.

The study discusses three initial empiric therapy regimens and suggests that identifying low-risk patients could allow for effective outpatient treatment, potentially lowering economic and psychological burdens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic Selection in the Treatment of Febrile Neutropenia: Current Approach and New Directions. Stefani, SD., Cadore, LP., Villaroel, RU., et al.[2019]

In a study of 124 adult cancer patients with febrile neutropenia in Lebanon, 86.23% received appropriate antibiotic therapy according to IDSA guidelines, indicating a generally good adherence to recommended practices for antibiotic use.

However, there was significant inconsistency in antifungal and antiviral treatments, with many patients receiving inappropriate drug choices, doses, and durations, highlighting a need for improved adherence to guidelines in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Antimicrobial Utilization among Cancer Patients with Febrile Neutropenia at the Lebanese Hospitals. Cherri, S., Malaeb, D., Shouman, L., et al.[2023]

Ambulatory management of febrile neutropenia is safe and shows improved quality of life for patients, making it a viable alternative to hospitalization.

This approach is also more cost-effective than traditional inpatient care, suggesting it could be a beneficial strategy for managing low-risk patients with febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambulatory management of low-risk febrile neutropenia in adult oncological patients. Systematic review. Forcano-Queralt, E., Lemes-Quintana, C., Orozco-Beltrán, D.[2023]

In a study of 536 episodes of febrile neutropenia across four Brazilian medical centers, vancomycin was underutilized, being administered in only 5% of cases despite guidelines recommending its use in 27% of instances.

The study highlights the need for better adherence to treatment guidelines for febrile neutropenia, as the low use of vancomycin could impact patient outcomes, especially given the presence of resistant infections like methicillin-resistant Staphylococcus aureus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers. Ramos, JF., Pereira, AD., Seiwald, MCN., et al.[2023]

In a study of 828 patients with febrile neutropenia, treatment with ceftriaxone alone resulted in a 70.8% response rate, significantly higher than the 56.9% response rate seen with combination therapy, indicating its efficacy as a single-agent treatment.

Ceftriaxone was found to be safe and effective, particularly in low-risk patients, suggesting that single-agent regimens could be a viable treatment option for managing febrile neutropenia in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. Karthaus, M., Wolf, HH., Kämpfe, D., et al.[2018]

In a study of 71 acute myeloid leukemia patients with febrile neutropenia, a short course of antibiotics (≤7 days) was found to be as effective as longer treatments for bloodstream infections, with only 7.6% of episodes relapsing within 30 days after stopping antibiotics.

The only significant risk factor for relapse was the duration of neutropenia, suggesting that managing neutropenia may be crucial in preventing infections, and these promising results warrant further investigation in prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study. Metais, A., Torregrosa Diaz, JM., Gallego Hernanz, MP., et al.[2023]

The implementation of the ECIL-4 antibiotic de-escalation protocol in 446 high-risk hematological patients led to a significant reduction in overall mortality (0.7% vs 2.7% in the historic cohort), indicating its effectiveness in improving patient outcomes.

Despite a higher incidence of bacteremia in the ECIL-4 group (46.9% vs 30.5%), there was no increase in severe complications like septic shock or ICU admissions, suggesting that the protocol is safe and does not compromise patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience. Verlinden, A., Jansens, H., Goossens, H., et al.[2022]

The management of febrile neutropenia has evolved significantly over the past 20 years, focusing on adapting treatment strategies to combat antibiotic-resistant strains and improving patient outcomes through better prognostic factors.

New approaches include the use of home therapy for select patients, the application of cytokines to enhance bone marrow recovery, and improved strategies for diagnosing and treating fungal infections associated with neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of neutropenic infection: trends towards monotherapy? Klastersky, J.[2019]

In a study of 180 neutropenic patients with positive blood cultures, the traditional antibiotic protocol (piperacillin, gentamicin, and cefazolin) was appropriate for 85% of bacteremia episodes, showing its continued relevance in treating febrile neutropenia.

The presence of antibiotic-resistant bacteria in patients was linked to higher mortality rates, highlighting the importance of using broad-spectrum antibiotic combinations to maximize treatment effectiveness in neutropenic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empiric antibiotic protocols for cancer patients with neutropenia: a single-center study of treatment efficacy and mortality in patients with bacteremia. Kleinhendler, E., Cohen, MJ., Moses, AE., et al.[2023]

References

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

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Incidence, treatment, and consequences of chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings. [2022]

3. Singapore pubmed.ncbi.nlm.nih.gov

Use of antibiotics in a haematology ward--an audit. [2020]

4. Brazil pubmed.ncbi.nlm.nih.gov

Antibiotic Selection in the Treatment of Febrile Neutropenia: Current Approach and New Directions. [2019]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Assessment of Antimicrobial Utilization among Cancer Patients with Febrile Neutropenia at the Lebanese Hospitals. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Ambulatory management of low-risk febrile neutropenia in adult oncological patients. Systematic review. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study. [2023]

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

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Treatment of neutropenic infection: trends towards monotherapy? [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Empiric antibiotic protocols for cancer patients with neutropenia: a single-center study of treatment efficacy and mortality in patients with bacteremia. [2023]