What to do if a patient has persistent leukocytosis (elevated White Blood Cell (WBC) count) and neutrophilia (elevated neutrophil count) despite vancomycin (vancomycin) treatment?

From the Guidelines

If a patient has persistent leukocytosis and neutrophilia despite vancomycin treatment, you should first reassess the infection source and consider broadening antibiotic coverage. Obtain new cultures (blood, urine, sputum, wound) to identify potential resistant organisms or secondary infections. Consider adding gram-negative coverage with piperacillin-tazobactam (4.5g IV every 6 hours) or meropenem (1g IV every 8 hours) as suggested by the Infectious Diseases Society of America guidelines 1. Check vancomycin trough levels to ensure they're therapeutic (15-20 mg/L for serious infections) and adjust dosing if needed, as recommended by the clinical practice guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children 1. Evaluate for non-infectious causes of leukocytosis such as steroids, malignancy, or inflammatory conditions. Look for undrained abscesses or other collections requiring surgical intervention. Consider infectious disease consultation for complex cases. Monitor inflammatory markers like CRP and procalcitonin to track response. Persistent elevation of white blood cells and neutrophils suggests either inadequate antimicrobial coverage, subtherapeutic drug levels, an unaddressed source of infection, or a non-infectious etiology. Vancomycin primarily covers gram-positive organisms, so infections with gram-negative bacteria, anaerobes, or fungi would not respond to vancomycin alone. Some key points to consider in the management of such patients include:

• The importance of broad-spectrum antibiotic coverage, including gram-negative and anaerobic coverage, especially in cases where the source of infection is not clearly identified 1.
• The need for careful monitoring of the patient's response to treatment, including regular assessment of white blood cell count, inflammatory markers, and clinical signs of infection 1.
• The potential for non-infectious causes of leukocytosis, such as malignancy or inflammatory conditions, which may require alternative management strategies 1. Given the complexity of these cases, consultation with an infectious disease specialist is often necessary to guide management and ensure the best possible outcomes for the patient.

From the FDA Drug Label

The median time to clearance in patients with MSSA was 4 days and in patients with MRSA was 8 days. Failure of treatment due to persisting or relapsing S aureus infections was assessed by the Adjudication Committee in 19/120 (16%) daptomycin for injection-treated patients (12 with MRSA and 7 with MSSA) and 11/115 (10%) comparator-treated patients (9 with MRSA treated with vancomycin and 2 with MSSA treated with an anti-staphylococcal semi-synthetic penicillin)

The FDA drug label does not directly answer the question of what to do if a patient has persistent leukocytosis and neutrophilia despite vancomycin treatment. However, it does provide information on the treatment of S. aureus bacteremia with vancomycin, including the median time to clearance and the rate of treatment failure due to persisting or relapsing infections 2.

• Key points:
  • The label does not provide guidance on managing persistent leukocytosis and neutrophilia.
  • Treatment failure due to persisting or relapsing S aureus infections occurred in 10% of vancomycin-treated patients.
  • Most patients who failed due to persisting or relapsing S aureus infection had deep-seated infection and did not receive necessary surgical intervention.

From the Research

Persistence of High WBCs and Neutrophils after Vancomycin Treatment

• The persistence of high White Blood Cell (WBC) counts and neutrophilia despite vancomycin treatment can be attributed to various factors, including the underlying infection, the patient's immune response, and the potential development of antibiotic resistance 3, 4.
• Vancomycin is a glycopeptide antibiotic effective against gram-positive bacterial infections, but its effectiveness can be limited by the emergence of resistant strains 3, 5.
• Studies have shown that vancomycin-resistant enterococcal bloodstream infections can be challenging to treat, and alternative antibiotics such as linezolid and daptomycin may be necessary 4, 6.
• The activity of vancomycin against coagulase-negative staphylococci (CNS) has been shown to be limited, with many strains exhibiting reduced susceptibility to vancomycin 5.
• Immunomodulatory properties of antibiotics, including vancomycin, linezolid, and daptomycin, can also influence the patient's immune response and potentially affect WBC counts and neutrophil levels 7.

Potential Causes of Persistent Leukocytosis and Neutrophilia

• Inadequate treatment of the underlying infection due to antibiotic resistance or insufficient antibiotic dosing 3, 4.
• Development of new infections or superinfections during vancomycin treatment 5, 6.
• Immunomodulatory effects of vancomycin and other antibiotics, which can influence the patient's immune response and cytokine production 7.
• Underlying medical conditions, such as sepsis or immunodeficiency, which can affect the patient's immune response and WBC counts 7, 6.

Considerations for Managing Persistent Leukocytosis and Neutrophilia

• Monitoring of WBC counts and neutrophil levels during vancomycin treatment to assess the patient's response to therapy 3, 4.
• Consideration of alternative antibiotics, such as linezolid or daptomycin, in cases of suspected antibiotic resistance or treatment failure 4, 6.
• Evaluation of the patient's underlying medical conditions and immune status to guide treatment decisions 7, 6.
• Consultation with infectious disease specialists or other experts to optimize treatment and management of persistent leukocytosis and neutrophilia 3, 4, 6.