3.06 - Febrile Neutropenia [updated]

Haematopoietic Stem Cell Transplantation (HSCT), Haematology and Oncology

Febrile Neutropenia: Neutrophils < 0.5 x 109/L, or < 1 x 109/L with a predicted decline to < 0.5 x 109/L,+ fever ≥ 38⁰C.

Low risk patients: Anticipate < 7 days profound neutropenia, no co morbidities, can take orally, accessible to hospital care.

High-risk patients: Anticipate ≥ 7 days and profound neutropenia (ANC < 1 x 109/L) ± significant medical co-morbid conditions.

A) Adults

B) Paediatrics

Disease / Etiology

Preferred

Alternative

Comments

Febrile Neutropenia

Gram positive:

Staph aureus / MRSA

Streptococcus spp

Enterococcus spp

Gram negative:

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa

Enterobacter spp

Acinetobacter baumanii

Strenotrophomonas maltophilia

Citrobacter spp

Fungal:

Candida spp

Aspergillus spp

Suspected in-dwelling venous catheter as source:

Staph aureus (MRSA)

Staph epidermidis (MRSE)

Non-neutropenic fever, stable patient, no previous infection, no infective foci:

Staph epidermidis (MSSE)

Staph aureus (MSSA)

Streptococcus viridians

Enterobacteriaceae

Pseudomonas

Enterococcus

Cloxacillin 50 mg/kg/dose (max 2gm) IV q6H

+

Gentamicin 5 mg/kg/dose (max 240 mg) IV q24H

Vancomycin 15 mg/kg (max 1gm) IV q8H

Stable Patient:

Piperacillin / Tazobactam 100 mg/kg/dose (Piperacillin component) (max 4 gm) IV q8H

For HSCT patients:

Cefepime 50 mg/kg/dose (max 2 gm) IV q8H

Unstable Patient / Previous MRSA Isolated:

Meropenem 20-40 mg/kg/dose

Ceftriaxone 50mg/kg/dose IV q12H

Monitor Vancomycin blood levels and renal function.

Documented fungaemia OR

No clinical improvement / febrile still after 96 hours of antibiotics

(max 2 gm) IV q8H

±

ADD Fluconazole 6-12mg/kg/dose IV q24H OR Amphotericin B 1 mg/kg IV q24H 4 - 6 hours infusion

Monitor renal function..

Vancomycin 15 mg/kg/dose (max 1 gm) IV q8H

Targeted Specific Pathogens

Candida spp

(Other than C. glabrata and C. krusei)

Aspergillus spp

Stenotrophomonas maltophilia

Pneumocystis jirovecii (PCP)

Co-trimoxazole 5 mg/kg/dose (Trimethoprim component) (max 160 mg) IV q6H

Pentamidine isethionate 4 mg/kg/dose IV q24H (given slowly over 1 hour in D5W)

Risk of severe hypotension

Duration of treatment: 21 days (can change to oral).

(Moderate to severe) Consider Prednisolone 1 - 2 mg/kg/day (max 80 mg) q12H in first week; then taper over next 2 weeks

Stable haemodynamics

Fluconazole 6-12 mg/kg/dose IV / PO q24H

Unstable haemodynamics, recent azoles exposure, unknown Candida spp

Micafungin 2mg/kg/dose (max 100 mg) IV q24H

Consider removal of CVC.

Repeat blood culture every 72 hours till a negative culture.

OR

Amphotericin B 1 mg/kg/dose IV q24H

Amphotericin B

1 - 1.5 mg/kg IV q24H

Co-trimoxazole 5 mg/kg/dose (Trimethoprim component) IV q6H

OR

Duration of treatment: ≥ 21 days on average or for 2 weeks following first negative blood culture.

Liposomal Amphotericin B is no more effective than Amphotericin B as an antifungal.

Lipid complex Amphotericin B 5mg/kg/dose IV q24H

Voriconazole 9 mg/kg/dose (max 350 mg) IV q12H x 2 doses followed by 8mg/kg/dose IV q12H

Fluconazole has no activity against Aspergillus spp.

Older children:

Renal function monitoring

Avoid Fluroquinolone group if possible < 18 years old. Risk of ruptured tendo-archilles and arthropathies.

Acinetobacter baumanii

Varicella zoster

Cytomegalovirus (CMV) Infection

Post-Exposure Prophylaxis

Effective up to 10 days following exposure.

Varicella Immunoglobulin (undetectable VZ antibodies) :

Ampicillin / Sulbactam

25 - 50 mg/kg/dose (Ampicillin component) IV q6H

Levofloxacin 8mg/kg/dose IV q12H

IV Immunoglobulin G (IVIG) 400 mg/kg.

Acyclovir 20mg/kg/dose PO q6H for 7 days

Treatment

Acyclovir 10 mg/kg/dose (max 800 mg) IV q8H for 7 - 10 days

Acyclovir 20mg/kg/dose PO q6h for 7 – 10 days or until no new lesions for 48 hours

Ganciclovir 5 mg/kg/dose IV q12h for 14 - 21 days