Canterbury DHB

Preventing Infections

The precautions described here often only apply when the neutrophil count is below 0.5 x10⁹/L. Although this is a general rule, there are exceptions.

• Bacterial prophylaxis is only given to standard allografts or when there are specific indications, e.g. previous perianal sepsis.
• Fungal prophylaxis is currently given continuously, i.e. continued between courses of chemotherapy.
• Viral prophylaxis is given in high risk situations and if the patient is HSV sero-positive or has had significant problems with herpetic infections.

Allografts are at particular risk of infection, due to a combination of neutropenia and immunosuppression, a risk exacerbated by GvHD and its treatment.

Low Bacterial Diet

A low bacterial diet should be commenced on admission and maintained regardless of blood counts until the whole intensive chemotherapy schedule has been completed. It should be continued until 6 weeks post-transplant for autologous BMT and at least 12 weeks post-transplant for allogeneic BMT – longer if significant graft versus host disease is present.

RIC patients require a low bacterial diet for 6 weeks or longer if significant GvHD. SCT recipients, and potential recipients should avoid sharing cups, glasses, and eating utensils with others, including family members. This is to decrease the risk of infections such as CMV, HSV, and EBV.

Bacterial Infections

• Staphylococcus aureus is a potentially pathogenic bacterium found in the nasal membranes, skin, hair follicles, and perineum. It can cause Hickman tunnel infections as well as life-threatening septicaemia.
  • Topical suppressive therapy after positive nasal swab:

    On or before their first admission to the unit, patients receiving intensive treatment (i.e. those with Hickman/PICC catheters) should be cultured for S. aureus with a nasal swab, in addition to MRSA swabs if also required. Those found to be carriers should be treated with prophylactic topical suppressive therapy (see below) for at least 1 week.

  • Topical suppressive therapy following or during active S. aureus infection:

    For patients receiving antibiotic treatment for an active S. aureus infection, topical suppressive therapy should be undertaken at the end of treatment except in the case of a Hickman line infection when this should be done concurrently (with the optical agents continuing beyond completion of the treatment course).

  • Topical suppressive treatment:

    Mupirocin 2% ointment applied to the anterior nares TDS, plus chlorhexidine 4% wash applied once daily as a skin wash and used as a shampoo twice weekly (all for at least 7 days). Octenidine skin wash may be used second-line to chlorhexidine for patients with sensitive or fragile skin. Triclosan is another alternative for those sensitive to chlorhexidine in the community but is not available in hospital. If an outpatient, washing and hot ironing of sheets every 1–2 days is recommended.

  • Download the S. aureus decolonisation patient information sheet.
• Ciprofloxacin is not used routinely for prophylaxis in intensively treated patients. Exceptions are patients undergoing allogeneic transplant and patients with a significant history of perianal infection who are receiving intensive treatment.

  These groups will have prophylaxis with ciprofloxacin 500 mg BD PO when neutrophils are <0.5 x 10⁹/L.

  Ciprofloxacin will normally stop when IV antibiotics are started, or when the neutrophil count rises above 0.5 x 10⁹/L.

• For allogeneic recipients, give phenoxymethylpenicillin 250–500 mg BD PO until initial immunisation programmes are completed (i.e. approximately 13 months post-SCT).

  See the post-transplant vaccination schedule. Reduce to 250 mg BD if nausea occurs.

  If allergic to penicillin, use roxithromycin 150 mg ONCE daily PO.

Hepatitis B Prevention

See Hepatitis B under Viral infection in SCT.

Herpetic Infections

Patients receiving intensive chemotherapy

• If there have been significant problems with herpes zoster (VZV) and/or the patient is herpes zoster sero-positive, give valaciclovir 500 mg TWICE daily.
• Patients receiving treatment for Acute Lymphoblastic Leukaemia, and patients taking proteasome inhibitors such as bortezomib and T-cell depleting agents such as alemtuzumab, should receive valaciclovir 500 mg TWICE daily.
• Otherwise, if there have been significant problems with herpes simplex in the past and/or the patient is herpes simplex (HSV) sero-positive, give valaciclovir 500 mg ONCE daily. If they do not fulfil these characteristics, they need not receive HZV/HSV prophylaxis.

  Note: Prophylactic dose if unable to tolerate oral tablets is aciclovir IV 5 mg 8 hourly.

All SCT Patients

These are at highest risk of developing both herpes simplex and herpes zoster (VZV) infections.

• Determine the HSV and VZV antibody status. If:
  • HSV and VZV antibody negative – no prophylaxis.
  • HSV +ve – only give valaciclovir 500 mg ONCE daily until Day +30.
  • VZV +ve – give valaciclovir 500 mg BD until Day +365.

  Note: If a patient on prophylactic valaciclovir is also treated with ganciclovir, the valaciclovir is discontinued.

Immunosuppressed patients who come into contact with chicken pox or shingles:

• Patients at highest risk for VZV infection in this situation:
  • Any allograft patient up to two years post-transplant
  • Any allograft patient with ongoing GvHD
  • Autologous patients up to six months post-transplant
  • Other intensively treated patients given purine analogues, e.g. fludarabine for six months following completion of chemotherapy.

  If these patients are sero-negative for VZV they should be given Zoster immunoglobulin as soon as possible. Varicella Zoster Immunoglobulin (ZIG) is available from NZBS. 200 IU/2 mL vial. Recommended dosage – Adults 6 mL IM.

  Note: If any of the above groups of patients develops a VZV-like rash after exposure to chicken pox or Herpes Zoster, they need urgent antivirals. The consultant will decide whether this should be IV aciclovir (if concerns re: malabsorption e.g. GvHD of gut) 10 mg/kg three times daily or PO valaciclovir 1000 mg TDS (with dose reduction if renal impairment).

Pneumocystis Prophylaxis

Pneumocystis jiroveci (previously known as carinii) is an opportunistic pathogen whose natural habitat is the lung.

Pneumocystis can proliferate to cause pneumonia in those who are very immunosuppressed, particularly those with low CD4+ T-cells, either due to underlying disease or due to potent T-lymphocytotoxic treatments, such as purine analogues, intensive chemotherapy and anti T-cell antibodies. Therefore patients at particular risk include those with acute lymphoblastic lymphoma, severe aplastic anaemia, transplants – both allogeneic and autologous – and intensively-treated lymphoproliferative disorders.

Indications for pneumocystic prohpylaxis

Without tests for quantifying CD4+ numbers and function, we cannot be absolutely sure which patients are sufficiently immunosuppressed that they should receive prophylactic treatment, but the general approach to pneumocystis prophylaxis outlined below should be followed:

• Patients receiving:
  • T-cell depleting purine analogues such as bendamustine, fludarabine, cladribine, gemcitabine, or pentostatin should receive pneumocystis prophylaxis throughout treatment and for six months from the end of treatment. In all indications, if patients remain very immunosuppressed, it may be appropriate to continue prophylaxis for longer and to have a high index of suspicion for symptoms such as dry cough, shortness of breath, or fever.
  • anti-T cell antibodies (e.g. alemtuzumab, antithymocyte immunoglobulin) should receive pneumocystis prophylaxis for 12 months after treatment.
  • treatment for acute lymphoblastic lymphoma should receive pneumocystis prophylaxis throughout treatment including maintenance treatment, and for six months from the end of treatment.
  • salvage therapies for relapsed or refractory lymphoid malignancies should receive pneumocystis prophylaxis throughout treatment, and for six months from the end of treatment.
  • treatment with a high intensity chemotherapy regimen for Non-Hodgkin lymphoma should receive pneumocystis prophylaxis throughout treatment, and for six months from the end of treatment. A high intensity regimen may be considered as a treatment that requires an inpatient admission for chemotherapy administration.
  • treatment with the combination of continuous oral cyclophosphamide and prednisone, or prolonged (> 1 month) treatment with significant (> 0.5 mg/kg prednisone equivalent) doses of steroids, should receive pneumocystis prophylaxis during these treatments.
• Pre-transplant allo and auto SCT patients are given pneumocystis prophylaxis. First line prophylaxis is trimethoprim + sulfamethoxazole 160 + 800 mg BD PO for 7 days before SCT (days -7 to -1). Pentamidine (dose as below) is a second line option as trimethoprim + sulfamethoxazole is contraindicated.
• Autologous SCT for lymphoma and myeloma should start pneumocystis prophylaxis when engraftment is established. Give for six months.
• Allogeneic SCT should start pneumocystis prophylaxis when engraftment is established. Give for 12 months or until they have stopped immunosuppressive therapy for GvHD (whichever is longer).
• Due to the methotrexate and trimethoprim + sulfamethoxazole interaction, patients receiving methotrexate concurrently should have pentamidine as first line treatment.

Medications for pneumocystis prophylaxis:

First line: trimethoprim + sulfamethoxazole 80 + 400 mg PO once daily.

If a patient does not tolerate this dose of trimethoprim + sulfamethoxazole, or if there is concern regarding the quality of engraftment, use a second or third line option as below until it is appropriate to resume trimethoprim + sulfamethoxazole.

Second line: Pentamidine 4 mg/kg IV 4 weekly. Dose is usually capped at 300 mg. Pentamidine is manufactured at a concentration of 2 mg/mL, in dextrose 5% or sodium chloride 0.9%, and is given over 2 hours. The HIV data indicates that if the period is extended beyond 4 weeks, protection is inadequate.

Third line: Dapsone 100 mg PO daily.

Due to the interaction between methotrexate and trimethoprim + sulfamethoxazole, patients receiving high dose methotrexate concurrently should have pentamidine as first line pnemocystis prophylaxis.

Pentamidine must be charted on the pentamidine prescription chart. If an inpatient, this should also be charted on MedChart as "infusion chart exists" (i.e. as a dummy drug) with the qualifier ‘pentamidine’ so there is an electronic record. Administration of pentamidine should also be included on the discharge summary. The pentamidine chart is then filed in the outpatient notes on discharge for future administrations.

See information about Treatment of Pneumocystis.

Topic Code: 9471