Neutropenic Patients and Neutropenic Regimes

Neutrophils are white blood cells and are plentiful in a normal circulation. They are crucial for a normal functioning immune system. They phagocytose organisms and their numbers increase in infections and inflammation, especially bacterial infections.

Neutropenia means a low neutrophil count. The normal range for neutrophils is 2.5 - 7.5x10⁹/L. In the 1960s it was first discovered that as the neutrophil count falls, especially once neutrophils < 1x10⁹/L, a patient becomes immunocompromised and at risk of serious infections which may be fatal.

When faced with a patient with neutropenia it is important to answer the following two questions:

1. What is the cause of neutropenic sepsis if present?
2. What is the underlying cause of neutropenia?

The causes of neutropenic sepsis can be bacterial, viral, or fungal (see box 4). In terms of the underlying cause of neutropenia this can be divided into congenital or acquired. Acquired causes include chemotherapy, bone marrow infiltration e.g. malignancy and viral infections (see box 5).

Neutropenic patients can be divided into 3 clinical groups

1. Immunocompetent patients presenting with neutropenia and compromised requiring urgent treatment.
2. Immunocompromised patients presenting with neutropenia and compromised requiring urgent treatment.
3. Otherwise well patients with neutropenia (these patients may be known to be neutropenic previously or presenting de novo and require investigation to look for an underlying diagnosis).

The most important concern is to determine whether the neutropenic patient is septic - this will require urgent and prompt management. A summary of this is as follows:

• Resuscitate the patient e.g. if hypovolaemic or septic shock is present.
• Does the patient have signs of sepsis e.g. fever, tachycardia, hypotension?
• Full history and examination (see box 1 and box 2 below).
• Send cultures (see box 3 for full list of investigations).
• Antibiotics - begin with broad spectrum according to local guidelines e.g. tazocin® and an aminoglycoside.
• Look for clues to the source of infection - if found then alter antibiotic regimen to more specific therapy (see box 4 below). Can even tailor therapy from the outset e.g. vancomycin in patients with known MRSA or acyclovir in cases of VZV / HSV infection.
• Discover the underlying cause for the neutropenia and treat if possible (see box 5 below).
• If patient is well or once patients have improved may need to consider prophylactic antibiotics and vaccinations. Will need to liaise with haematology and microbiology specialists.
• Immunosuppressed patients will need careful consideration of further management issues e.g. prophylactic antibiotics.

• Acute Respiratory distress syndrome - commonly associated with viridans group streptococci (VGC).
• Disseminated intravascular coagulation (DIC).
• Multiple organ failure.

Other points to note

• Over the last few decades the organisms involved in neutropenic sepsis have changed, organisms such as enterococci and legionella are becoming more frequent.
• Also there is an increased resistance to antibiotics such as pseudomonas species resistant to imipenem.
• At present there is no role for the use of prophylactic antibiotics in patients with chronic neutropenia in whom there are no symptoms or signs of infection.⁵

• If neutropenia is chronic and the patient is not displaying any infective symptoms then discuss with haematology specialist.
• Reverse barrier nursing is required.
• Treat all with broad spectrum antibiotics (according to local policy) if acute neutropenia or a rapidly falling neutrophil count with fever.
• Some treat all with a neutrophil count < 500, even if no fever - see local hospital guidelines or discuss with haematologists/microbiologists.
• Dual therapy is mainstay (once all cultures sent) - but do not delay if patient septic e.g.gentamicin and antipseudomonal cover (e.g. tazocin®).
• A systematic review and meta-analysis comparing β-lactam and aminoglycoside combination versus β-lactam alone found no difference between the two.⁶ Superinfections were also similar in both groups.
• There is recent evidence for monotherapy with imipenem provided patient not shocked or if pseudomonas species grown.²
• If ongoing fever consider other organisms such as fungi and further investigations such as ultrasonography or CT scanning looking for abdominal collections.
• Most patients are admitted and treated for 7 - 14 days or until neutrophil count improves. They may be converted to oral therapy once they are apyrexial. Oral therapies include ciprofloxacin and co-amoxiclav.
• Infections associated with chronic neutropenia can be treated on an out-patient basis under specialist advice. Oral antibiotics have also been used in low risk cancer patients with neutropenia.⁷

• G-CSF is a growth factor that is given subcutaneously and can stimulate the bone marrow thus leading to an increased number of white cells.
• In some cases G-CSF is used prophylactically e.g. following chemotherapy.
• In neutropenic patients with an infection G-CSF can be given to help counteract the infection along with antibiotics.
• G-CSF shortens the time taken for the neutrophil count to recover.^7,8
• Treatment with G-CSF is usually reserved for neutropenia associated with severe (high risk of deterioration) or recurrent infections. However the evidence at present does not show any clear benefit for the use of G-CSF.⁷
• Side-effects of G-CSF include pain and itchiness at the site of injection. It can itself cause fever, diarrhoea and vomiting.