What are the next steps for a 7-year-old with PANS (Pediatric Acute-onset Neuropsychiatric Syndrome)/PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) who completed 14 days of prophylactic azithromycin (azithromycin) yesterday, but now presents with mouth pain, red dots on the mouth and palate, and mood changes after exposure to a confirmed strep infection?

Immediate Evaluation and Testing for Active Streptococcal Infection

Your child needs immediate testing with a rapid antigen detection test (RADT) or throat culture to determine if she has active streptococcal pharyngitis, as the red dots (petechiae) on her palate combined with mouth pain and mood changes suggest possible breakthrough strep infection despite prophylactic azithromycin. 1

Why Testing is Critical Now

• The clinical presentation of palatal petechiae (red dots on the palate) is a classic sign of streptococcal pharyngitis and warrants immediate diagnostic testing 1
• Mood changes in a child with PANS/PANDAS history following strep exposure strongly suggests either active infection or an inflammatory flare 2
• Azithromycin prophylaxis may not have prevented infection, particularly given that some streptococcal strains are resistant to macrolides, with resistance varying geographically 1, 3
• The FDA label for azithromycin explicitly states that "some strains are resistant to azithromycin" and "susceptibility tests should be performed when patients are treated with azithromycin" 3

Immediate Next Steps

If RADT or culture is positive for Group A Streptococcus:

• Switch immediately to penicillin-based therapy, as penicillin remains the treatment of choice with no documented resistance anywhere in the world 1
• Prescribe amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for a full 10 days 1, 4
• Alternative: Benzathine penicillin G intramuscular injection (single dose: 600,000 units if <27 kg; 1,200,000 units if ≥27 kg) provides guaranteed compliance 1
• The full 10-day course is mandatory regardless of symptom improvement to prevent rheumatic fever and potentially reduce PANDAS flare risk 1, 4

If testing is negative but clinical suspicion remains high:

• Consider empiric treatment with amoxicillin given the high-risk PANS/PANDAS history and classic presentation 1, 2
• The PANS/PANDAS Consortium recommends "an initial course of anti-streptococcal treatment for all newly diagnosed PANS cases" and vigilance for streptococcal infections in known PANS patients 2
• Monitor closely for neuropsychiatric symptom escalation over the next 48-72 hours 2

Why Azithromycin May Have Failed

• Macrolide resistance in Group A Streptococcus, while <5% in the United States overall, does exist and varies by region 1, 3
• Azithromycin is listed as having only "moderate" quality evidence for strep pharyngitis treatment, compared to "high" quality evidence for penicillin-based therapies 1
• The FDA label notes that azithromycin "should not be relied upon" for certain streptococcal complications and that "data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available" 3
• For PANDAS patients specifically, penicillin-based antibiotics are preferred over macrolides for both treatment and prophylaxis 2

Monitoring for PANS/PANDAS Flare

• Document baseline neuropsychiatric symptoms immediately: obsessive-compulsive behaviors, tics, hyperactivity, anxiety, mood lability, and any choreiform movements 2, 5
• The current mood changes may represent early flare symptoms, as PANDAS/PANS can manifest with acute behavioral deterioration following streptococcal exposure even with prophylaxis 2, 6
• Contact your child's PANS/PANDAS specialist or psychiatrist to alert them of the potential exposure and current symptoms 2
• Consider non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief and potential anti-inflammatory benefit, though avoid aspirin in children 1, 7

Critical Pitfalls to Avoid

• Do not assume the prophylactic azithromycin was adequate treatment - it was intended for prevention, not treatment of active infection, and may not eradicate established strep pharyngitis 1, 3
• Do not delay testing - waiting to see if symptoms worsen risks both medical complications and PANS/PANDAS flare progression 1, 2
• Do not use another course of azithromycin - switch to penicillin-based therapy given possible macrolide resistance and superior efficacy 1, 3
• Do not stop antibiotics early if symptoms improve - the full 10-day course is essential for complete bacterial eradication and prevention of complications 1, 4

Household Contact Considerations

• Screen the 4-year-old sister to ensure her strep infection has been adequately treated and eradicated 1
• While routine testing of asymptomatic household contacts is not recommended, your 7-year-old's PANS/PANDAS diagnosis and current symptoms make this a "special circumstance" warranting heightened vigilance 1, 2

Long-Term Prophylaxis Discussion

• After this acute episode resolves, discuss with your PANS/PANDAS specialist whether chronic secondary antimicrobial prophylaxis is indicated 2
• The PANS/PANDAS Consortium suggests "chronic secondary antimicrobial prophylaxis for children with PANDAS who have severe neuropsychiatric symptoms or recurrent group A Streptococcus-associated exacerbations" 2
• If prophylaxis is continued, penicillin-based options are preferred over macrolides due to the absence of resistance 1, 2