Why shouldn't a proton‑pump inhibitor be co‑prescribed with antibiotics in otherwise healthy children without a documented acid‑related disorder such as gastro‑oesophageal reflux disease or peptic ulcer?

Why PPIs Should Not Be Co-Prescribed with Antibiotics in Healthy Children

Proton pump inhibitors should not be routinely prescribed alongside antibiotics in otherwise healthy children because PPIs are only indicated for documented acid-related disorders (GERD, peptic ulcer disease), not for antibiotic-related gastrointestinal side effects, and their use significantly increases the risk of serious infections in young children. 1, 2

Core Principle: PPIs Require Specific Indications

• PPIs are explicitly indicated only for patients with diagnosed gastroesophageal reflux disease (GERD), not for uncomplicated physiologic gastroesophageal reflux or prophylactic gastrointestinal protection 1
• Lifestyle changes should be emphasized as first-line therapy for both GER and GERD before considering any medication 1
• There is no evidence-based indication for using PPIs to prevent antibiotic-associated gastrointestinal symptoms in children 1

Significant Safety Concerns in Pediatric Populations

Infection Risk Profile

The most compelling reason to avoid unnecessary PPI use is the substantially elevated infection risk:

• PPI use is associated with a 34% increased risk of serious infections overall in young children (adjusted HR 1.34,95% CI 1.32-1.36) 2

• Specific infection risks include:

  • Digestive tract infections: 52% increased risk (aHR 1.52) 2
  • Ear, nose, and throat infections: 47% increased risk (aHR 1.47) 2
  • Lower respiratory tract infections: 22% increased risk (aHR 1.22) 2
  • Bacterial infections: 56% increased risk (aHR 1.56) 2
  • Viral infections: 30% increased risk (aHR 1.30) 2

• Evidence suggests acid suppression with PPIs may be a risk factor for community-acquired pneumonia, gastroenteritis, and candidemia 1

• In preterm infants, PPIs may increase the risk of necrotizing enterocolitis 1

Mechanism of Harm

• PPIs alter the microbiota and may have direct immunosuppressive effects, making children more vulnerable to infections during antibiotic therapy when microbial balance is already disrupted 2
• The combination of antibiotics (which disrupt normal flora) and PPIs (which reduce gastric acid barrier and alter immunity) creates a particularly high-risk scenario 2

Clinical Decision Algorithm

Step 1: Assess for Documented Acid-Related Disorder

• Does the child have confirmed GERD with gastrointestinal symptoms (recurrent regurgitation, dystonic neck posturing in infants, heartburn/epigastric pain in older children)? 3
• Does the child have documented peptic ulcer disease or erosive esophagitis? 3
• If NO to both: Do not prescribe PPIs 3, 1

Step 2: If Acid-Related Disorder Present

• Treatment for GERD should not be used when there are no GI clinical features of GERD (Grade 1B recommendation) 3
• For children with confirmed GERD, start with lifestyle modifications first 1
• Consider PPI therapy only after conservative measures fail, for 4-8 weeks maximum, with mandatory reevaluation 1

Step 3: Antibiotic Co-Administration

• If a child requires antibiotics and has no documented acid-related disorder: prescribe antibiotics alone 1
• If a child has pre-existing, documented GERD already on PPI therapy and requires antibiotics: continue existing PPI regimen only 1
• Never initiate PPIs prophylactically with antibiotics in children without documented acid-related pathology 1

Evidence Quality and Strength

• The recommendation against PPI use without documented GERD is a Grade 1B (strong recommendation, moderate quality evidence) from the American College of Chest Physicians 3
• The 2023 nationwide French cohort study of over 1.2 million children provides robust evidence of infection risks, with median follow-up of 3.8 years 2
• Multiple guideline societies (American Academy of Pediatrics, American Academy of Family Physicians, American College of Chest Physicians) consistently recommend against empiric PPI use 1

Common Pitfalls to Avoid

• Overprescription is rampant: Studies show PPIs are prescribed for 11% of hospitalized children, with only 34.5% compliance with recommendations 4
• Misdiagnosis of normal infant reflux as GERD: PPIs are not effective in reducing GERD symptoms in infants and should not be used for physiologic reflux 5, 1
• Prophylactic use misconception: There is no evidence supporting PPI use to prevent antibiotic-associated gastrointestinal symptoms 1
• Duration errors: If PPIs are indicated, treatment should not exceed 8-12 weeks without re-evaluation 1

Special Considerations

• For infants under 1 year: PPIs are particularly ineffective for symptom reduction and carry disproportionate infection risks 5, 2
• Serious adverse events, particularly lower respiratory tract infections, were significantly higher in PPI-treated infants compared to controls 1
• The American Academy of Pediatrics specifically recommends against using PPIs for infants with symptomatic GERD aged one month to less than one year 1