What antibiotic should be added to Zosyn (Piperacillin/Tazobactam) for a patient with leukocytosis and neutrophilia, but no known source of infection?

Management of Leukocytosis and Neutrophilia with No Identified Source of Infection

For a patient with rising white count, neutrophilia, negative blood cultures, and no identifiable source of infection who is already on Zosyn (piperacillin/tazobactam), vancomycin should be added as empiric therapy. 1

Assessment of Current Situation

When evaluating a patient with leukocytosis and neutrophilia without a clear source:

• Current antibiotics: Patient is already on Zosyn (piperacillin/tazobactam), which provides broad-spectrum coverage including Pseudomonas
• Workup completed: Blood cultures negative x2, chest and urine evaluations clear
• Clinical concern: Rising white count and neutrophilia despite current therapy

Recommended Antibiotic Addition

First-line recommendation:

• Add vancomycin (30-60 mg/kg/day in 2-4 divided doses) 1
• Target serum trough concentrations of 15-20 μg/mL for severe infections
• Monitor renal function closely due to potential nephrotoxicity

Rationale for adding vancomycin:

1. Empiric administration of vancomycin is strongly recommended when a patient has persistent fever or worsening clinical status despite broad-spectrum beta-lactam therapy 1
2. Vancomycin provides coverage for resistant gram-positive organisms including MRSA that may not be covered by Zosyn
3. The Expert Committee of the WHO Essential Medicines recommends adding vancomycin to piperacillin-tazobactam for high-risk patients with persistent fever 1

Alternative Options if Vancomycin is Contraindicated

If the patient has a history of vancomycin allergy or other contraindications:

• Daptomycin (4-6 mg/kg/day) 1
• Linezolid (600 mg every 12 hours) 1
• Ceftaroline 1

Antifungal Consideration

If fever persists for 5-7 days despite antibacterial therapy and neutropenia is not resolving:

• Consider adding empiric antifungal therapy 1
• Options include:
  • Echinocandin (first choice)
  • Fluconazole (800 mg loading dose, then 400 mg daily) if Candida parapsilosis is suspected
  • Liposomal amphotericin B (3-5 mg/kg/day) for broader coverage 1

Monitoring and Follow-up

• Reassess clinical response within 48-72 hours after adding vancomycin
• Monitor complete blood count daily to track neutrophil trends
• Check vancomycin trough levels before the 4th dose
• Monitor renal function due to potential nephrotoxicity with vancomycin (occurs in approximately 9% of patients) 1

Duration of Therapy

• Continue antibiotics until patient is afebrile for at least 48 hours
• For most bacterial infections, 7-14 days of therapy is recommended 1
• Consider discontinuing vancomycin by day 3 if cultures remain negative and there is no evidence of gram-positive infection 1

Important Cautions

• Long-term vancomycin use (>21 days) has been associated with neutropenia in some cases 2, 3, 4
• If neutropenia worsens after adding vancomycin, consider this as a potential adverse effect
• Avoid aminoglycosides as empiric therapy due to nephrotoxicity concerns unless specifically indicated 1, 5

By adding vancomycin to the current Zosyn regimen, you provide comprehensive coverage against potential resistant gram-positive organisms while maintaining the broad gram-negative coverage of piperacillin/tazobactam.