What are the potential side effects of antibiotics in children with pneumonia?

Side Effects of Antibiotics in Children with Pneumonia

The most common side effects of antibiotics used for pediatric pneumonia include gastrointestinal symptoms (diarrhea, nausea, vomiting), skin rashes, and thrush, with serious adverse events being rare but including allergic reactions, hepatotoxicity, and Clostridium difficile-associated diarrhea. 1, 2

Common Side Effects by Antibiotic Class

Beta-Lactams (Amoxicillin, Ampicillin, Cephalosporins)

• Gastrointestinal disturbances are the most frequent adverse effects, including diarrhea, nausea, and abdominal discomfort 2
• Skin rashes occur in approximately 5-10% of children treated with amoxicillin, though most are non-allergic maculopapular eruptions 2
• Thrush (oral candidiasis) can develop during or after treatment 2
• True allergic reactions including urticaria, angioedema, and anaphylaxis are rare but potentially life-threatening 3

The CAP-IT trial demonstrated that adverse events (including thrush, skin rashes, and diarrhea) occurred at similar rates regardless of amoxicillin dose (35-50 mg/kg/day vs. 70-90 mg/kg/day) or duration (3 vs. 7 days), suggesting these side effects are not dose-dependent within therapeutic ranges 2

Macrolides (Azithromycin, Clarithromycin, Erythromycin)

• Gastrointestinal effects are common, particularly with erythromycin, including nausea, vomiting, abdominal pain, and diarrhea 1
• QT interval prolongation is a serious concern that can lead to cardiac arrhythmias and torsades de pointes, though fatal cases are rare 1
• Hepatotoxicity including abnormal liver function, hepatitis, cholestatic jaundice, and rarely hepatic failure have been reported with azithromycin 1
• Serious allergic reactions including angioedema, anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis occur rarely but can be fatal 1

Clindamycin (for MRSA Coverage)

• Clostridium difficile-associated diarrhea (CDAD) is a significant risk with clindamycin use, ranging from mild diarrhea to fatal colitis 1
• Gastrointestinal symptoms are common 3

Serious but Rare Adverse Events

Clostridium Difficile-Associated Diarrhea

• CDAD can occur with nearly all antibacterial agents used for pneumonia treatment and may develop up to 2 months after antibiotic administration 1
• Hypertoxin-producing strains cause increased morbidity and mortality and may require colectomy 1
• Any child presenting with diarrhea following antibiotic use requires careful evaluation for CDAD 1

Cardiac Effects

• Macrolides carry risk of QT prolongation which is particularly concerning in children with pre-existing cardiac conditions, electrolyte abnormalities, or those on other QT-prolonging medications 1
• At-risk groups include those with known QT prolongation, history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, or uncorrected hypokalemia/hypomagnesemia 1

Hepatotoxicity

• Azithromycin can cause hepatic injury ranging from abnormal liver function tests to hepatic failure, requiring immediate discontinuation if hepatitis signs develop 1

Antimicrobial Resistance Considerations

• Nasopharyngeal colonization with penicillin-non-susceptible pneumococci occurs at similar rates regardless of amoxicillin dose or duration (3 vs. 7 days) 2
• The impact on the broader microbiome and selection of resistant organisms remains an important consideration when prescribing antibiotics 4, 5

Key Clinical Pitfalls

• Reappearance of allergic symptoms may occur when symptomatic treatment is discontinued, even without further antibiotic exposure, due to azithromycin's long tissue half-life 1
• Masking of incubating syphilis can occur with macrolides used for short courses, requiring serologic testing in sexually active adolescents 1
• Drug interactions with macrolides include elevated digoxin levels, acute ergot toxicity with ergotamine, and interactions with terfenadine, cyclosporine, and phenytoin 1

Monitoring Recommendations

• Discontinue antibiotics immediately if signs of serious allergic reaction, hepatitis, or severe diarrhea develop 1
• Careful monitoring is warranted in children with risk factors for QT prolongation when macrolides are prescribed 1
• Prolonged observation may be required for allergic reactions to azithromycin due to its extended tissue half-life 1