Can Bactrim (trimethoprim/sulfamethoxazole) cause neutropenia?

Bactrim (Trimethoprim/Sulfamethoxazole) and Neutropenia

Yes, Bactrim (trimethoprim/sulfamethoxazole) can cause neutropenia, which can range from mild to severe and even life-threatening agranulocytosis in some cases. 1

Mechanism and Risk

Trimethoprim/sulfamethoxazole (TMP-SMX) can cause neutropenia through several mechanisms:

1. Antifolate action: Trimethoprim inhibits granulopoiesis through its antifolate effects, which can suppress bone marrow production of neutrophils 2
2. Immune-mediated reactions: TMP-SMX can trigger immune responses affecting neutrophil production or survival
3. Direct bone marrow suppression: Particularly in patients with folate deficiency or increased folate requirements

Incidence and Severity

The hematologic adverse effects of TMP-SMX include:

• Agranulocytosis
• Aplastic anemia
• Thrombocytopenia
• Leukopenia
• Neutropenia
• Hemolytic anemia
• Megaloblastic anemia 1

Studies have shown:

• Up to 34% of children treated with TMP-SMX for 10 days developed neutropenia (defined as neutrophil count ≤1,500/mm³) 3
• Even low-dose prophylactic regimens can cause neutropenia, particularly in young children 4
• Severe cases of agranulocytosis with absolute neutrophil counts of 0 have been reported in otherwise healthy adults 5

Risk Factors

Patients at higher risk for TMP-SMX-induced neutropenia include:

• Patients with folate deficiency
• Individuals with increased folate requirements
• Young children (especially under 2 years of age) 4
• Patients receiving prolonged courses of therapy
• Patients with HIV/AIDS
• Patients with renal insufficiency

Monitoring and Management

For patients on TMP-SMX therapy:

1. Monitor blood counts: Consider biweekly complete blood counts for patients on prolonged therapy 3
2. Discontinue at first sign of significant neutropenia: TMP-SMX should be stopped immediately if severe neutropenia develops 1
3. Consider folinic acid supplementation: Studies show that folinic acid (leucovorin) can prevent or reverse TMP-SMX-induced neutropenia 2, 4
4. G-CSF for severe cases: In severe neutropenia, granulocyte colony-stimulating factor may produce a dramatic neutrophil response 6

Clinical Implications

In cancer patients and those with neutropenia, guidelines acknowledge the risk but still recommend TMP-SMX for Pneumocystis jirovecii pneumonia (PJP) prophylaxis when indicated 7. However, the guidelines recommend careful monitoring and consideration of alternative agents in high-risk patients.

Important Caveats

1. Neutropenia from TMP-SMX typically resolves after discontinuation of the drug, usually within 1-2 weeks 5, 3
2. The risk of neutropenia must be balanced against the benefits of TMP-SMX, particularly in immunocompromised patients requiring PJP prophylaxis
3. Avoid concomitant use of TMP-SMX with other medications that can cause bone marrow suppression when possible
4. The FDA drug label specifically lists agranulocytosis and neutropenia among the hematologic adverse reactions to TMP-SMX 1

When prescribing TMP-SMX, clinicians should be vigilant for signs of neutropenia, particularly in high-risk patients, and should have a low threshold for checking complete blood counts if symptoms of infection or other concerns arise.