EMPIRIC TREATMENT OF FEBRILE NEUTROPENIA

ADULT FEBRILE NEUTROPENIC PATIENT 9 ANC < 1.0 x 10 /L (& expected to further decline) AND O O ORAL TEMPERATURE ≥ 38.3 C OR ≥ 38.0 C for ≥ 1 hour

LOW RISK HIGH RISK

May treat as outpatient Admit

Features: Features: 9 . Absolute neutrophil count > 0.1 x 10 /L . Age > 70 years 9 . Absolute monocyte count > 0.1 x 10 /L . Inpatient status at time of fever

. Normal findings on a chest radiograph . Significant medical comorbidity or clinically

. Nearly normal liver and renal function tests unstable, e.g., hypotension, COPD,

. Duration of neutropenia ≤ 7 days hypoxia, new onset abdominal pain,

. Resolution of neutropenia expected in < 10 neurological changes, dehydration, etc.

days . Anticipated prolonged severe neutropenia: 9 . No intravenous catheter site infection ANC ≤ 0.1 x 10 /L for > 7 days

. Early evidence of bone marrow recovery . Serum creatinine > 176 µmol/L

. Malignancy in remission . Liver function tests > 3 x upper normal limit o . Peak temperature of < 39.0 C . Uncontrolled, progressive cancer

. No neurological or mental changes . Pneumonia or other complex infections . No abdominal pain, or appearance of illness . Mucositis grade > 2 . No comorbid complications, e.g., shock, . Poor performance status (ECOG > 1) hypoxia, pneumonia, serious infection, etc. . Intravenous catheter site infection

INTERMEDIATE RISK

(Neither low nor high risk)

Consider admitting patient

OUTPATIENT INPATIENT THERAPY

ADDITIONAL CRITERIA: RECOMMENDED ANTIBIOTICS: . Reliable PATIENT, who can return to the facility easily (Please check local hospital FORMULARY) . Can take oral medications and fluids (Hotlink to recommended doses) . Can be easily contacted for daily assessment . Intravenous PIPERACILLIN-TAZOBACTAM, OR . Can be admitted urgently, if clinically unwell/unstable . Intravenous IMIPENEM OR MEROPENEM, OR . Intravenous CEFEPIME OR CEFTAZIDIME (NOT recommended as monotherapy in areas at risk for RECOMMENDED ANTIBIOTICS: extended-spectrum beta-lactamases [ESBL] (Hotlink to recommended doses) producing bacteria) . ORAL CIPROFLOXACIN + ORAL . Intravenous AMINOGLYCOSIDE (e.g., Tobramycin / AMOXICILLIN/CLAVULANATE Gentamicin) OR CIPROFLOXACIN may be added to . If anaphylaxis allergy to beta-lactams, consider ORAL the initial empiric antibiotic regimen, if resistance is CIPROFLOXACIN + ORAL CLINDAMYCIN suspected or if there are complications (e.g., . CIPROFLOXACIN not recommended, if significant hypotension, persistent fever, pneumonia, etc.) patient exposure in the past 3 months . Intravenous VANCOMYCIN may be added, in the . Not recommended for children – see guidelines following situations: hemodynamic instability or . OTHERS – ADMIT (See Recommended Antibiotics sepsis, pneumonia, positive blood culture for gram- under HIGH RISK section) positive organism, catheter-related infection, skin or soft tissue infection, known or suspected MRSA, . FORMALLY RE-EVALUATE PATIENT IN 2 to 3 DAYS. severe mucositis while receiving fluoroquinolone . IF AFEBRILE for > 48 HOURS, AND NEUTROPHILS > prophylaxis. Stop Vancomycin in 48 hrs, if not 0.5 X 10 9/ L for 2 consecutive days and increasing, no indicated. positive source of infection identified and patient . If anaphylaxis allergy to beta-lactams, treat with clinically stable, may discontinue antibiotics and monitor VANCOMYCIN + AMINOGLYCOSIDE + patient. CIPROFLOXACIN.

. IF FEBRILE, admit patient for further investigations and IF POSSIBLE, AVOID AMINOGLYCOSIDES OR OTHER initiation of appropriate antimicrobial therapy. NEPHROTOXIC AGENTS IN PATIENTS, RECEIVING CISPLATIN OR OTHER NEPHROTOXIC CHEMOTHERAPY. Additional notes: . Empirical ANTIFUNGAL therapy should be considered in patients, . These guidelines are compiled from the published literature and who are experiencing persistent fevers, despite receiving 3-5 days current practice (Hotlink to references). of broad-spectrum antibiotic therapy. . For more information, please contact Dr. Shirin Abadi at . METRONIDAZOLE may be added to empirical IV antibiotics, if [email protected] anaerobic infection (e.g., intra-abdominal) is suspected. . To contact individual BCCA Centres, please call: . Antimicrobial therapy should be continued until the infection has Abbotsford (AC): 604-851-4710, Kelowna (CSI): 250-712-3900, resolved and the patient is no longer neutropenic. Prince George (CN): 250-645-7300, Surrey (FVC): 604-930-2098, . In the absence of serious infections, G-CSF is not indicated to Vancouver (VC): 604-877-6000, Victoria (VIC): 250-519-5500. improve clinical outcomes, but may reduce hospitalization by 1 day.

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