EMPIRIC TREATMENT OF FEBRILE NEUTROPENIA

ADULT FEBRILE NEUTROPENIC PATIENT

ANC < 1.0 x 109/L (& expected to further decline) AND
ORAL TEMPERATURE 38.3 OC OR 38.0 OC for 1 hour

LOW RISK
May treat as outpatient

HIGH RISK
Admit

Features:
Absolute neutrophil count > 0.1 x 109 /L
Absolute monocyte count > 0.1 x 109 /L
Normal findings on a chest radiograph
Nearly normal liver and renal function tests
Duration of neutropenia 7 days
Resolution of neutropenia expected in < 10
days
No intravenous catheter site infection
Early evidence of bone marrow recovery
Malignancy in remission
Peak temperature of < 39.0 oC
No neurological or mental changes
No abdominal pain, or appearance of illness
No comorbid complications, e.g., shock,
hypoxia, pneumonia, serious infection, etc.

Features:
Age > 70 years
Inpatient status at time of fever
Significant medical comorbidity or clinically
unstable, e.g., hypotension, COPD,
hypoxia, new onset abdominal pain,
neurological changes, dehydration, etc.
Anticipated prolonged severe neutropenia:
ANC 0.1 x 109 /L for > 7 days
Serum creatinine > 176 mol/L
Liver function tests > 3 x upper normal limit
Uncontrolled, progressive cancer
Pneumonia or other complex infections
Mucositis grade > 2
Poor performance status (ECOG > 1)
Intravenous catheter site infection

INTERMEDIATE RISK
(Neither low nor high risk)
Consider admitting patient

OUTPATIENT
THERAPY
ADDITIONAL CRITERIA:
Reliable PATIENT, who can return to the facility easily
Can take oral medications and fluids
Can be easily contacted for daily assessment
Can be admitted urgently, if clinically unwell/unstable

RECOMMENDED ANTIBIOTICS:
(Hotlink to recommended doses)
ORAL CIPROFLOXACIN + ORAL
AMOXICILLIN/CLAVULANATE
If anaphylaxis allergy to beta-lactams, consider ORAL
CIPROFLOXACIN + ORAL CLINDAMYCIN
CIPROFLOXACIN not recommended, if significant
patient exposure in the past 3 months
Not recommended for children see guidelines
OTHERS ADMIT (See Recommended Antibiotics
under HIGH RISK section)
FORMALLY RE-EVALUATE PATIENT IN 2 to 3 DAYS.
IF AFEBRILE for > 48 HOURS, AND NEUTROPHILS >
0.5 X 10 9/ L for 2 consecutive days and increasing, no
positive source of infection identified and patient
clinically stable, may discontinue antibiotics and monitor
patient.
IF FEBRILE, admit patient for further investigations and
initiation of appropriate antimicrobial therapy.

INPATIENT

RECOMMENDED ANTIBIOTICS:
(Please check local hospital FORMULARY)
(Hotlink to recommended doses)
Intravenous PIPERACILLIN-TAZOBACTAM, OR
Intravenous IMIPENEM OR MEROPENEM, OR
Intravenous CEFEPIME OR CEFTAZIDIME (NOT
recommended as monotherapy in areas at risk for
extended-spectrum beta-lactamases [ESBL]
producing bacteria)
Intravenous AMINOGLYCOSIDE (e.g., Tobramycin /
Gentamicin) OR CIPROFLOXACIN may be added to
the initial empiric antibiotic regimen, if resistance is
suspected or if there are complications (e.g.,
hypotension, persistent fever, pneumonia, etc.)
Intravenous VANCOMYCIN may be added, in the
following situations: hemodynamic instability or
sepsis, pneumonia, positive blood culture for grampositive organism, catheter-related infection, skin or
soft tissue infection, known or suspected MRSA,
severe mucositis while receiving fluoroquinolone
prophylaxis. Stop Vancomycin in 48 hrs, if not
indicated.
If anaphylaxis allergy to beta-lactams, treat with
VANCOMYCIN + AMINOGLYCOSIDE +
CIPROFLOXACIN.
IF POSSIBLE, AVOID AMINOGLYCOSIDES OR OTHER
NEPHROTOXIC AGENTS IN PATIENTS, RECEIVING
CISPLATIN OR OTHER NEPHROTOXIC CHEMOTHERAPY.

Additional notes:
Empirical ANTIFUNGAL therapy should be considered in patients,
who are experiencing persistent fevers, despite receiving 3-5 days
of broad-spectrum antibiotic therapy.
METRONIDAZOLE may be added to empirical IV antibiotics, if
anaerobic infection (e.g., intra-abdominal) is suspected.
Antimicrobial therapy should be continued until the infection has
resolved and the patient is no longer neutropenic.
In the absence of serious infections, G-CSF is not indicated to
improve clinical outcomes, but may reduce hospitalization by 1 day.

These guidelines are compiled from the published literature and

current practice (Hotlink to references).
For more information, please contact Dr. Shirin Abadi at
SAbadi@bccancer.bc.ca
To contact individual BCCA Centres, please call:
Abbotsford (AC): 604-851-4710, Kelowna (CSI): 250-712-3900,
Prince George (CN): 250-645-7300, Surrey (FVC): 604-930-2098,
Vancouver (VC): 604-877-6000, Victoria (VIC): 250-519-5500.

Disclaimer Both the format and content of the guidelines will change as they are reviewed and revised on a periodic basis. Any physician using these guidelines to provide treatment
for patients will be solely responsible for verifying the doses, providing the prescriptions, and administering the medications described in the guidelines, according to acceptable
standards of care.

EMPIRIC TREATMENT OF FEBRILE NEUTROPENIA

.

SUGGESTED DOSING FOR ANTIBIOTICS (IN ADULT PATIENTS WITH NORMAL

RENAL FUNCTION):
Amoxicillin/Clavulanate

PO 500/125 mg Q8H, OR 875/125 mg Q12H

Cefepime

IV

2 g Q8H

Ceftazidime

IV

2 g Q8H

Ciprofloxacin

IV

400 mg Q8-12H

PO 750 mg Q12H
Clindamycin

PO 600 mg Q8H

Gentamicin OR
Tobramycin

IV

6-7 mg/kg Q24H (if CrCl > 60 mL/minute, otherwise

use caution & prolong dosing interval)

Imipenem

IV

500 mg Q6H

Meropenem

IV

1 g Q8H

Piperacillin/Tazobactam IV

4.5 g Q6H

Ticarcillin/Clavulanate

IV

3.1 g Q4-6H

Vancomycin

IV

25 mg/kg IV loading dose, followed by 15 mg/kg

Q12H (round to nearest 250 mg dose)

Metronidazole

IV

500 mg Q12H

References:
1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with
cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011;52(4):e56-e93.
2. Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults
treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2013;31(6):794-810.
3. in:DN Gilbert, RC Moellering Jr, GM Eliopoulos, HF Chambers, MS Saag (Eds.). The Sanford Guide to Antimicrobial Therapy 2013.
43rd ed. Antimicrobial Therapy, Inc. Sperryville, VA; 2013.
4. National Comprehensive Cancer Network (NCCN). (2013). Prevention and Treatment of Cancer-Related Infections v.1. Retrieved
May 26th, 2014, from http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf.
5. Bow E, Wingard JR. Overview of neutropenic fever syndromes. In: UpToDate, Marr KA , Thorner AR (Eds), UpToDate, Waltham, MA.
(Accessed on May 26th, 2014).
6. Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: A
multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000;18(16):3038-51.

Approved on: March 26th, 2015

Disclaimer Both the format and content of the guidelines will change as they are reviewed and revised on a periodic basis. Any physician using these guidelines to provide treatment
for patients will be solely responsible for verifying the doses, providing the prescriptions, and administering the medications described in the guidelines, according to acceptable
standards of care.