In a well‑appearing, afebrile 2‑month‑old infant with a lymphocyte‑predominant leukocytosis of 21 000 cells/µL and no focal signs, should empiric antibiotics be started?

No, Starting Antibiotics Was Not Correct

In a well-appearing, afebrile 2-month-old infant with lymphocyte-predominant leukocytosis (WBC 21,000) and no focal signs of infection, empiric antibiotics should NOT be initiated while awaiting culture results 1.

Clinical Reasoning

The decision to withhold antibiotics in this case is based on the 2021 AAP guidelines for febrile infants 8-60 days old, which can be extrapolated to this afebrile infant with isolated leukocytosis:

Key Criteria Met for Withholding Antibiotics

According to guideline KAS 19d, clinicians need not use antimicrobial therapy while awaiting bacterial culture results when ALL of the following are met 1:

• CSF analysis (if obtained) is normal or enterovirus-positive
• Urinalysis is negative
• No inflammatory markers obtained are abnormal
• Infant is well-appearing

Why This Case Does Not Warrant Antibiotics

1. No fever present: The infant is afebrile, which significantly reduces the pre-test probability of serious bacterial infection

2. Well-appearing: Clinical appearance is the most critical factor. The guidelines emphasize that well-appearing infants with negative workup have an extremely low risk of bacteremia (0.1% for infants 29-60 days) 1

3. No focal signs: Clear chest, no otitis media, no other abnormal findings on examination

4. Lymphocyte-predominant leukocytosis: This pattern is more consistent with viral infection rather than bacterial infection. The elevated WBC with lymphocyte predominance suggests a viral etiology, possibly enterovirus or another viral illness

The Risk-Benefit Analysis

Benefits of withholding antibiotics 1:

• Minimizes risk of adverse treatment consequences
• Reduces impact on developing microbiome
• Contributes to antimicrobial stewardship
• Avoids unnecessary hospitalization and family disruption

Risks of unnecessary antibiotics:

• Adverse drug reactions
• Disruption of infant's evolving microbiome
• Acceleration of antimicrobial resistance
• Potential for hospital-acquired infections if admitted

What Should Have Been Done Instead

The appropriate management pathway 1:

1. Obtain appropriate cultures: Blood culture, urine culture (by catheterization if urinalysis positive), and consider CSF if any concern

2. Observe without antibiotics: The infant can be managed at home or with brief observation if:

   • Parents can return promptly if condition changes
   • Follow-up arranged within 24 hours
   • Parents understand warning signs

3. Reassess at 24-36 hours: Check culture results and clinical status

4. Initiate targeted therapy only if cultures positive 1: If bacterial pathogen identified, treat with appropriate antimicrobial for the specific organism

Important Caveats

Antibiotics WOULD be indicated if 1:

• CSF analysis suggests bacterial meningitis
• Any inflammatory markers are abnormal
• Urinalysis is positive
• Infant develops fever or clinical deterioration
• Infant is not truly well-appearing on careful examination

The Evidence on Leukocytosis Alone

While extreme leukocytosis (>25,000) in febrile children 3-36 months is associated with increased risk of serious bacterial infection, particularly pneumonia 2, this infant is:

• Afebrile (not febrile)
• 2 months old (younger than the studied population)
• Has lymphocyte predominance (suggesting viral rather than bacterial etiology)
• Has clear chest examination (no pneumonia)

The WBC count of 21,000 with lymphocyte predominance in an afebrile, well-appearing infant without focal findings does not meet the threshold for empiric treatment.

Antimicrobial Stewardship Principle

The 2021 AAP guidelines explicitly state that the benefit-harm assessment shows a preponderance of benefit in withholding antibiotics when criteria are met 1. Recent evidence confirms that deferring antibiotics in appropriately selected well-appearing infants results in decreased antibiotic use without affecting the rate of invasive bacterial infections or need for escalation of care 3.

Bottom Line

The on-call doctor's decision to start antibiotics was not correct. The appropriate approach would have been to obtain cultures, observe the infant closely with clear return precautions, and arrange timely follow-up. Antibiotics should only be initiated if cultures return positive or if the infant's clinical status deteriorates.