What are the clinical trials for pediatric infectious diseases?

From the Guidelines

Clinical trials in pediatric infectious diseases are crucial for developing safe and effective treatments, and researchers must prioritize age-appropriate dosing, ethical considerations, and special monitoring protocols to ensure the best possible outcomes for children. When conducting such trials, researchers must consider the unique physiological needs of children, which often differ from those of adults. For example, amoxicillin for pediatric pneumonia is typically dosed at 90 mg/kg/day divided into two doses for 5-7 days, rather than adult dosing 1.

Key Considerations

• Age-appropriate dosing is essential to ensure the safety and efficacy of treatments in children
• Ethical considerations, including robust informed consent processes and age-appropriate assent, are paramount in pediatric clinical trials
• Special monitoring protocols are necessary to detect adverse effects that may present differently in children than adults
• Recruitment often occurs through pediatric hospitals, clinics, and infectious disease specialists

Treatment Options

• Oseltamivir is approved for treatment of children as young as 2 weeks of age and is recommended for treatment of influenza in both term and preterm infants from birth 1
• Zanamivir is administered by inhalation using a proprietary "Diskhaler" device and is not recommended for people with chronic respiratory diseases 1
• Peramivir is given as a single 600-mg IV infusion over 15-30 minutes for adults and children 2-12 years old 1

Diagnosis and Management

• Influenza diagnostic tests vary by method, availability, processing time, sensitivity, and cost, and clinical judgment is an important factor in treatment decisions 1
• Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a definitive influenza test result 1

From the FDA Drug Label

CLINICAL STUDIES Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media In two adequate and well-controlled U. S. clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years The clinical cure rates and statistical outcome appear in the table below: Table 5 Clinical Efficacy in Pediatric Patients with Acute Bacterial Otitis Media Clinical Efficacy in Evaluable Population Study DayCeftriaxone Single DoseComparator – 10 Days of Oral Therapy95% Confidence IntervalStatistical Outcome Study 1 – U.S. amoxicillin/clavulanateCeftriaxone is lower than control at study day 14 and 28. 1474%(220/296)82%(247/302)(-14.4%, -0.5%) 2858%(167/288)67%(200/297)(-17.5%, -1.2%) Study 2 – U.S.1TMP-SMZCeftriaxone is equivalent to control at study day 14 and 28. 1454%(113/210)60%(124/206)(-16.4%, 3.6%) 2835%(73/206)45%(93/205)(-19.9%, 0. 0%) An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens The results of this study are tabulated as follows: Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen: Table 6 Bacteriologic Eradication Rates by Pathogen Study Day 13 to 15Study Day 30+2 OrganismNo. AnalyzedNo. Erad. (%)No. AnalyzedNo. Erad (%) Streptococcus pneumoniae3832 (84)3525 (71) Haemophilus influenzae3328 (85)3122 (71) Moraxella catarrhalis1512 (80)159 (60)

The clinical trials in pediatric patients with acute bacterial otitis media showed that ceftriaxone had varying degrees of efficacy compared to oral antibiotics.

• In Study 1, ceftriaxone was lower than control at study day 14 and 28.
• In Study 2, ceftriaxone was equivalent to control at study day 14 and 28. The bacteriologic eradication rates for common pathogens were:
• Streptococcus pneumoniae: 84% at study day 13-15 and 71% at study day 30+2
• Haemophilus influenzae: 85% at study day 13-15 and 71% at study day 30+2
• Moraxella catarrhalis: 80% at study day 13-15 and 60% at study day 30+2 2

From the Research

Clinical Trials for Pediatric Infectious Diseases

• The treatment of community-acquired pneumonia in pediatric patients is a significant concern, with various antibiotics being used to treat the condition 3, 4.
• A study published in 1995 compared the efficacy and safety of sparfloxacin, amoxycillin-clavulanic acid, and erythromycin in treating community-acquired pneumonia, finding that the overall success rates for the three antibiotics were similar 3.
• Another study published in 2024 discussed the diagnosis and treatment of community-acquired pneumonia, highlighting the importance of testing for COVID-19 and influenza, and using empirical antibacterial therapy to cover the most likely bacterial pathogens 5.

Antibiotic Stewardship in Pediatrics

• Antibiotic overuse contributes to antibiotic resistance, making antibiotic stewardship a crucial practice in pediatrics 6.
• A policy statement published in 2021 provided guidance for inpatient and outpatient antibiotic stewardship programs, emphasizing the importance of prescribing antibiotics only when necessary and promoting the use of appropriate agents, doses, and durations of therapy 6.
• A study published in 2000 discussed antimicrobial regimens for infants and children, highlighting the emergence of bacteria resistant to commonly used antimicrobial agents and the need for newer drugs and formulations 7.

Treatment Options for Community-Acquired Pneumonia

• Various antibiotics, including cefuroxime, ceftriaxone, and amoxicillin-clavulanic acid, have been compared in the treatment of community-acquired pneumonia, with no statistically significant differences found in the evolution of patients treated with these antibiotics 4.
• A study published in 1998 found that amoxicillin-clavulanic acid represented an empirical treatment of choice for community-acquired pneumonia 4.
• The use of β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, has been recommended for hospitalized patients with suspected bacterial community-acquired pneumonia and without risk factors for resistant bacteria 5.