What is the appropriate management for a 3‑year‑old child who, after three days of oral amoxicillin‑clavulanic acid and regular paracetamol for cough, cold and fever, now has recurrent high fever, leukopenia with relative neutropenia and a negative C‑reactive protein?

Management of Leukopenia and Neutropenia Following Amoxicillin-Clavulanate Therapy in a 3-Year-Old

Immediately discontinue amoxicillin-clavulanate, as this child has developed drug-induced neutropenia, a recognized adverse effect of beta-lactam antibiotics that typically resolves within 7–14 days after stopping the offending agent. 1

Understanding the Clinical Picture

This presentation is characteristic of antibiotic-induced neutropenia rather than ongoing bacterial infection:

• The negative CRP on day 4 indicates resolution of the acute bacterial inflammatory process, making ongoing bacterial infection unlikely 2
• Leukopenia (WBC 3000) with relative neutropenia (45%) translates to an absolute neutrophil count of approximately 1350/mm³, which represents moderate neutropenia 1
• The recurrent fever despite initially settling is likely a manifestation of drug-induced bone marrow suppression rather than treatment failure 1
• Beta-lactam antibiotics, including amoxicillin-clavulanate, are well-documented causes of neutropenia, even after short courses of 3–7 days 1

Immediate Management Steps

Stop amoxicillin-clavulanate immediately and do not substitute another beta-lactam antibiotic at this time 1

Obtain a complete blood count with differential within 24–48 hours to document the trajectory of neutrophil recovery 1

Monitor for signs of secondary infection during the neutropenic period, including:

• New fever patterns (temperature >38.5°C or rigors) 3
• Oral mucositis or new mouth lesions 3
• Perianal tenderness or skin breakdown 3
• Respiratory deterioration or new infiltrates 3

When to Restart Antibiotics

Do NOT restart antibiotics empirically unless the child develops new signs of bacterial infection during neutrophil recovery 3

If new fever or clinical deterioration occurs during neutropenia, hospitalize immediately and initiate broad-spectrum IV therapy:

• Ceftriaxone 50–100 mg/kg/day IV (avoiding amoxicillin-clavulanate and other beta-lactams that caused the neutropenia) 4, 5
• Add vancomycin 40–60 mg/kg/day IV every 6–8 hours if the child appears toxic or has risk factors for MRSA 4, 5

Expected Recovery Timeline

Neutrophil counts typically normalize within 7–14 days after discontinuing the causative antibiotic 1

Fever related to drug-induced neutropenia usually resolves within 48–72 hours of stopping the medication 1

Repeat CBC at 48–72 hours, then weekly until neutrophil count returns to >1500/mm³ 3

Critical Pitfalls to Avoid

Do not assume treatment failure and escalate to broader antibiotics when the CRP is negative and the clinical picture suggests drug toxicity rather than resistant infection 2, 1

Do not continue or switch to another beta-lactam (such as cefixime or cefdinir) in this setting, as cross-reactivity for neutropenia exists across the beta-lactam class 1

Do not delay stopping the antibiotic while awaiting specialist consultation—immediate discontinuation is the definitive treatment for drug-induced neutropenia 1

Specific Guidance for This Case

For this 3-year-old child:

• Stop amoxicillin-clavulanate now 1
• Continue paracetamol for symptomatic fever control 6
• Recheck CBC in 48 hours to confirm neutrophil recovery is beginning 1
• If fever persists beyond 48 hours after stopping the drug OR if new clinical signs of infection appear, obtain blood cultures and hospitalize for IV ceftriaxone 50–100 mg/kg/day 4, 5
• If neutrophils drop below 500/mm³ (severe neutropenia), hospitalize immediately for empiric broad-spectrum IV antibiotics regardless of fever, as the risk of life-threatening bacterial infection rises sharply 3

Long-Term Considerations

Document this adverse reaction clearly in the child's medical record as "amoxicillin-clavulanate-induced neutropenia" to prevent future re-exposure 1

Avoid all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems) for at least 3–6 months; if beta-lactam therapy is absolutely required in the future, use only under close hematologic monitoring 1

For future respiratory infections in this child, consider azithromycin 10 mg/kg day 1, then 5 mg/kg days 2–5 as first-line therapy to avoid beta-lactam re-exposure 4, 5