Does Unasyn (Ampicillin/Sulbactam) cause leukopenia?

Unasyn (Ampicillin/Sulbactam) and Leukopenia

Yes, Unasyn (ampicillin/sulbactam) can cause leukopenia, particularly with prolonged use at high doses. This adverse effect is consistent with the known hematological side effects of penicillin-class antibiotics.

Mechanism and Risk Factors

• Penicillin-related antibiotics, including ampicillin/sulbactam combinations, can cause leukopenia as an infrequently recognized complication 1
• The risk of leukopenia increases significantly with:
  • Higher doses (≥150 mg/kg/day) 1
  • Longer duration of therapy (≥2 weeks) 1
  • Advanced age 2
  • Renal or hepatic dysfunction 2

Timing and Incidence

• Leukopenia is unusual within the first week of antibiotic treatment 1
• Most cases (67%) develop after two or more weeks of high-dose therapy 1
• The exact incidence rate for Unasyn specifically is not well-documented, but penicillin-class antibiotics as a group are known to cause this adverse effect 1, 3

Monitoring Recommendations

• Baseline complete blood count (CBC) should be obtained before starting Unasyn therapy 2
• For standard short-course therapy (≤7 days), routine monitoring may not be necessary 1
• For patients receiving:
  • High doses (≥150 mg/kg/day)
  • Extended therapy (>1 week)
  • Those with renal/hepatic impairment
  • Elderly patients
  • Careful monitoring of CBC is recommended 2, 1

Clinical Presentation and Management

• Leukopenia may present as decreased white blood cell count, particularly neutrophils 3
• The major danger of neutropenia is the increased risk of infection 3
• Management approach:
  • Identify the cause (drug-induced in this case) 3
  • Consider discontinuation or dose reduction of Unasyn if significant leukopenia develops 1
  • In cases of febrile neutropenia, prompt initiation of empiric antimicrobial therapy is essential 4
  • For severe cases with high infection risk, granulocyte colony-stimulating factor (G-CSF) may be considered 2

Important Caveats

• Leukopenia may not always require immediate discontinuation of therapy, as spontaneous recovery can occur in some cases 5
• However, if white blood cell count progressively decreases, the antibiotic should be stopped 5
• Patients who develop leukopenia with one penicillin-class antibiotic may be at higher risk with other antibiotics in the same class 1
• Concurrent hepatic dysfunction may be observed alongside leukopenia in some patients receiving antimicrobial therapy 5