Short vs Standard Antibiotics for Childhood Pneumonia

Overseen By Khaled AL zubaidi, MD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Medical College of Wisconsin

Disqualifiers: Hemodynamic instability, Respiratory support, Immunocompromised, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 5-14 days

236 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this open label, randomized, non-inferiority clinical trial is to compare the treatment success of a 5 day antibiotic course versus a standard antibiotic course (usually 7-14 days of antibiotics) in hospitalized children aged 3 months to 18 years, with uncomplicated community acquired pneumonia. The main questions it aims to answer are: * Does a 5 day course work as well as standard (longer) courses of antibiotics for treating community acquired pneumonia in children? * Does a 5 day course cause less antibiotic side effects compared to a standard (longer) course of antibiotics in children with community acquired pneumonia? Participants will * be randomly assigned to either receive 5 total days or a total duration decided by the treating physician * receive a brief follow up questionnaire regarding clinical symptoms, follow up care/antibiotics, and side effects via phone or email at days 5 and 14 from the start of antibiotics Researchers will compare the experimental group (receiving 5 days duration) with the control group (standard duration) to see if 5 days is as successful as a standard duration.

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 focuses on comparing different durations of antibiotic treatment for pneumonia in children.

What data supports the effectiveness of the drug for treating childhood pneumonia?

Research shows that amoxicillin combined with clavulanic acid is effective against various infections, including those caused by drug-resistant bacteria like Streptococcus pneumoniae, which is a common cause of pneumonia. High-dose amoxicillin/clavulanate has been shown to be effective in treating respiratory infections in children, suggesting it could be beneficial for childhood pneumonia as well. ^{1 2 3 4 5}

Is the combination of amoxicillin and clavulanic acid safe for children?

Amoxicillin combined with clavulanic acid is generally well tolerated in children, with mild gastrointestinal disturbances like diarrhea being the most common side effect. No serious safety concerns have been reported in studies involving children. ^{2 4 6 7 8}

How does the drug amoxicillin/clavulanate differ from other treatments for childhood pneumonia?

Amoxicillin/clavulanate is unique because it combines amoxicillin with clavulanic acid, which helps overcome bacterial resistance by inhibiting beta-lactamase enzymes. This combination has shown better clinical efficacy in treating bacterial pneumonia in children compared to amoxicillin alone, especially against penicillin-resistant strains of bacteria. ^{3 4 6 9 10}

Research Team

Michelle Mitchell

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for hospitalized children aged 3 months to 18 years with uncomplicated community-acquired pneumonia. They must not have taken antibiotics before hospitalization and should be able to take oral medication or receive injections.

Inclusion Criteria

I stabilized within 3 days after starting antibiotics, without needing extra oxygen and no fever.

My scans show signs of pneumonia.

I have been diagnosed with a simple case of pneumonia caught outside of a hospital.

Exclusion Criteria

I needed help with breathing for more than 72 hours.

Non-English speakers

Inability to adhere to follow up

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a 5-day or standard duration antibiotic course for community-acquired pneumonia

5-14 days

Follow-up

Participants' parents/guardians receive a follow-up questionnaire on days 5 and 14 to assess clinical improvement and side effects

14 days

2 contacts (phone/email)

Treatment Details

Interventions

• Amoxicillin
• Amoxicillin-clavulanate
• Ampicillin for Injection
• Ampicillin / Sulbactam Injection
• Cefprozil
• Ceftriaxone for Injection
• Clindamycin
• Levofloxacin

Trial Overview The study tests if a shorter, 5-day antibiotic treatment is as effective as the standard longer course (7-14 days) in treating pneumonia in children. Participants are randomly assigned to one of the two durations and followed up through questionnaires on days 5 and 14.

Participant Groups

Group I: Short course antibiotic duration Experimental Treatment 8 Interventions

The participants in this group will receive a total antibiotic course of 5 days including the number of days received during their hospital admission and following hospital admission combined.

Group II: Standard of care antibiotic duration Active Control 8 Interventions

Participants will receive the standard-of-care antibiotic course in this group. That is, the duration of antibiotics will be decided by the primary treating physician in this group. The antibiotic course will include the number of days received during the participant's hospital admission and following hospital admission combined.

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

Approved in European Union as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections
• Ear, nose and throat infections

Approved in United States as Amoxicillin for:

• Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract

Approved in Canada as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

Amoxicillin/clavulanate 2000/125 mg, designed to maintain effective drug levels over a 12-hour period, showed a high clinical success rate of 94.4% against penicillin-resistant Streptococcus pneumoniae (PRSP) in patients with respiratory infections, based on data from 10 clinical studies involving over 6,400 participants.

The treatment was particularly effective against PRSP strains with elevated amoxicillin MICs (4-8 mg/L), achieving a success rate of 96.2% in patients with these resistant strains, demonstrating its efficacy in overcoming antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance in practice: bacteriological efficacy in patients with drug-resistant S. pneumoniae. Garau, J.[2019]

In a study of 200 children with mild to severe pyodermas, amoxicillin plus clavulanic acid showed a high clinical cure rate of 96% in severe cases, outperforming other antibiotics like co-trimoxazole, which had a cure rate of only 52%.

Amoxicillin combined with clavulanic acid was well tolerated, with only mild diarrhea reported in 4% of cases, indicating a favorable safety profile for this treatment in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of amoxicillin and clavulanic acid in the treatment of pyoderma in children. Kar, PK.[2010]

Increasing the pediatric amoxicillin dose from 45 mg/kg to 90 mg/kg while keeping clavulanate at 6.4 mg/kg/day significantly improved the efficacy of amoxicillin-clavulanate against penicillin-resistant strains of Streptococcus pneumoniae in a rat pneumonia model.

The higher dose effectively reduced bacterial counts for strains with lower amoxicillin minimum inhibitory concentrations (MICs of 2 and 4 microg/ml), while the lower dose was only effective against the strain with an MIC of 2 microg/ml, indicating that higher doses can enhance treatment outcomes against resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae. Woodnutt, G., Berry, V.[2020]

Amoxicillin, introduced in 1974, is more effective than ampicillin for treating infections due to its ability to maintain higher and longer-lasting serum concentrations, making it a preferred choice for various bacterial infections.

The combination of amoxicillin with clavulanate (Augmentin) has proven particularly effective for treating pediatric infections like acute otitis media (AOM), with a high-dose formulation introduced in 2001 to better address the needs of pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin/clavulanate for infections in infants and children: past, present and future. Klein, JO.[2019]

Ampicillin/sulbactam is highly effective against a range of pediatric infections, including respiratory, urinary, skin, and bone infections, and has shown continued effectiveness against common pathogens despite resistance issues.

Sultamicillin, the oral form of ampicillin/sulbactam, has excellent tolerability and low treatment discontinuation rates, making it a preferred choice for managing pediatric infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ampicillin/sulbactam and sultamicillin in pediatric infections: a re-evaluation. Dajani, A.[2017]

Amoxicillin/clavulanic acid (Augmentin) is effective against common pathogens causing acute otitis media (AOM) in children, including penicillin-resistant strains, and has shown similar or better clinical response rates compared to other antibiotics in randomized trials involving pediatric patients aged 1 to 6 years.

The high-dose formulation of amoxicillin/clavulanic acid is well tolerated with a low incidence of adverse events (3.6%), making it a suitable treatment option for recurrent or persistent AOM, especially when resistant bacteria are suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. Easton, J., Noble, S., Perry, CM.[2018]

In a study involving 31 patients undergoing elective laparoscopy, both ampicillin with sulbactam and amoxicillin with clavulanic acid were administered intravenously, achieving effective antimicrobial concentrations in serum and peritoneal fluid within 2 hours.

The concentrations of these antibiotics reached levels that are known to be effective against bacteria in laboratory settings, suggesting their potential efficacy in preventing infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penetration of sulbactam-ampicillin and clavulanic acid-amoxicillin into the pelvic peritoneum. Houang, ET., Colley, N., Chapman, M.[2021]

Sultamicillin, a prodrug combining ampicillin and sulbactam, showed no safety concerns in a study of 144 subjects, indicating it is safe for treating acute otitis media.

The clinical efficacy of sultamicillin was similar to that of amoxicillin-clavulanate, with no significant differences in effusion clearance at 10 or 30 days, suggesting it could be a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of sultamicillin and amoxicillin-clavulanate: treatment of acute otitis media. Chan, KH., Bluestone, CD., Tan, LS., et al.[2019]

In a study of 100 children with bacterial pneumonia, those treated with amoxycillin plus clavulanic acid showed significantly better improvement in symptoms like chest pain and fever by Day 3 compared to those treated with amoxycillin alone.

The combination treatment had a higher overall clinical efficacy rate of 93.8%, compared to 60.4% for amoxycillin alone, with only two mild adverse reactions reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid ('Augmentin') in the treatment of bacterial pneumonia in children. Jibril, HB., Ifere, OA., Odumah, DU.[2019]

In a study of 71 hospitalized pediatric patients aged 1 month to 16 years, intravenous and sequential intravenous-oral clavulanate-potentiated amoxycillin therapy was found to be effective, leading to clinical cure in all patients with various bacterial infections.

The treatment was generally safe, with only mild adverse effects reported, including phlebitis (6%), gastrointestinal issues (6%), and rash (4%), indicating that amoxycillin/clavulanate is a reliable option for treating serious bacterial infections in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential intravenous-oral amoxycillin/clavulanate (Augmentin) therapy in paediatric hospital practice. Schaad, UB., Pfenninger, J., Wedgewood-Krucko, J.[2019]

References

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

Performance in practice: bacteriological efficacy in patients with drug-resistant S. pneumoniae. [2019]

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

A combination of amoxicillin and clavulanic acid in the treatment of pyoderma in children. [2010]

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

Efficacy of high-dose amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae. [2020]

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

Amoxicillin/clavulanate for infections in infants and children: past, present and future. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Use of ampicillin/sulbactam and sultamicillin in pediatric infections: a re-evaluation. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. [2018]

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

Penetration of sulbactam-ampicillin and clavulanic acid-amoxicillin into the pelvic peritoneum. [2021]

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

Comparative study of sultamicillin and amoxicillin-clavulanate: treatment of acute otitis media. [2019]

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

An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid ('Augmentin') in the treatment of bacterial pneumonia in children. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Sequential intravenous-oral amoxycillin/clavulanate (Augmentin) therapy in paediatric hospital practice. [2019]