FEVER and NEUTROPENIA

Updated Summer 2018 - By Menachem Spira with Peter Cole and Vijaya Soma

Adapted from: https://sites.google.com/site/montepeds2/feverandneutropenia

Please also refer to the Antimicrobial Management Guidelines for Fever and Neutropenia in Pediatric Oncology from the Pediatric Infectious Diseases Department for specific guidance on antibiotic choice and management.

 

Fever and neutropenia is a common cause of admission to CHAM 9. You will most often encounter these patients while on the Heme-Onc rotation, but it's not a bad idea to get into the habit of calculating the ANC on every patient to ensure that they are not neutropenic.

 

Definitions (IDSA Guidelines)

Fever: 1 oral temp ≥ 38.3°C (101°F) OR an oral temp of  ≥38.0°C (100.4°F) for longer than 1 hour OR 2 elevations >38.0°C (100.4°F) within a 12 hour period.

Neutropenia in pediatric cancer patients: ANC <500 cells/microL or an ANC <1000 cells/micoL that is expected to decrease to <500 cells/microL during the next 48 hours.

ANC = WBC × (% neutrophils + % bands)

 

          

Diagnosis

What to ask in the history:

  • Important to determine what is the cause of neutropenia.

    • What kind of cancer is the patient being treated for?

      • Cancer history – when diagnosed, previous course etc.

      • What kind of chemotherapy and when it was last received:

        • Important to assess how long the patient will be neutropenic and whether you should expect the ANC to increase or decrease.

        • Generally, neutrophil nadir expected 7-10 days from the start of chemotherapy, and lasts 5-7 days

        • Some chemotherapies are not expected to cause significant neutropenia (e.g. vincristine, asparaginase, antibody-based therapy)

    • Ever have fever and neutropenia before:

      • What infections has the patient had in the past?

      • Critical for modifying empiric antibiotic to cover previously isolated or resistant strains

    • Details of the patient’s history can usually be obtained through Epic – look for the last Heme-Onc clinic visit or the Heme-Onc admission note from the patient’s last admission note.

  • Attempt to determine if the patient has a reason for being febrile:

    • Localizing symptoms

      • URI symptoms, cough, otitis

      • Diarrhea (think C. Diff)

      • Abdominal pain (think typhlitis/neutropenic enterocolitis)

      • UTI symptoms

      • Rectal pain on defecation (think of perirectal abscess)

      • Headache/neck stiffness (meningitis)

      • Pain over central line site

    • Exposures

      • Sick contacts

      • Pets

      • Travel

 

What to look for on physical exam:

  • Check the vital signs to look for signs of shock, SIRS criteria (may be blunted in neutropenic patients) and continue to monitor closely!

    • In addition to blood pressure/pulse, check capillary refill

  • Note patient’s general appearance.

    • Presence of chills?

  • Make sure to look for any sources of infection:

    • Thorough physical exam including: oropharynx, teeth, TMs, sinuses, skin, perianal area (visual exam only)

      • Abdominal tenderness (RLQ) can be a sign of typhlitis (neutropenic enterocolitis)

    • Special attention to sites of any indwelling lines the patient may have:

      • Know the type of line/port and how many ports are present

Initial Tests:

  • Initial blood work to be drawn include:

    • CBC, with differential (make sure to calculate ANC)

    • Basic metabolic panel (BUN, creatinine)

    • Type and Screen (must be renewed every 3 days)

      • Obtain consent early for blood products if you anticipate the need for transfusion in the future

    • Other tests as appropriate: electrolytes, LFTs, amylase, lipase

  • Microbiology

    • Blood cultures from each lumen of any indwelling catheters (ports, PICC, etc)

      • Make sure each culture is labeled accurately before sending to lab

    • Urine culture (non-catheterized) and urinalysis, if patient is symptomatic

    • Consider C. diff., rotavirus, or viral cultures as indicated by symptomatology

  • Imaging

    • Chest X-ray (PA & Lateral, not portable) for all patients

    • Consider KUB, abdominal CT, sinus CT, as indicated by symptomatology

 

Management:

  • Stabilize the patient

    • If patient is hypotensive, bolus them (20mL/kg of NS)

      • A patient requiring a bolus for hypotension should be evaluated by the PICU → call PMET

      • If patient does not respond to boluses/transfusions will likely need to be in ICU (for drips)

      • If patient requires ≥3 boluses within a short period of time, be careful of fluid overloading the patient

    • If patient is anemic, transfuse with pRBCs if readily available

  • Antibiotic Therapy

    • Antibiotic therapy should selected be as per guidelines by the Pediatric Infectious Disease Department found here: Link

    • Typically, the initial agent for febrile neutropenia without clear source is cefepime 50 mg/kg/dose IV q8h (max 2000 mg/dose)

      • Ideally this should be administered within one hour of presentation

  • Once an etiology is obtained (i.e. positive culture) tailor the antibiotic therapy based on pathogen sensitivity

    • All neutropenic patients with a positive blood culture should have an ID consult

    • If a positive culture is found from a multi-lumen catheter, make sure that antibiotics are being rotated through ALL lumens of the catheter– including the infected lumen

  • If fever, chills or hypotension persistently occur with accessing an indwelling line – stop using the line and strongly consider having the line removed!

    • If patient has a line infection, consider removing line if:

      • Repeated infections with same bacteria

      • Fungal infection

      • Inability to clear infection

  • Labs during admission

    • Most patients with fever and neutropenia will have an indwelling catheter – if so, all blood draws (unless contraindicated) should be done through their line by the nurse. Make sure to select “Unit Collect” in the order on Epic

    • Daily CBC, with differential to check ANC

    • If no source is initially identified and patient remains febrile, continue to obtain daily blood cultures

      • Multiple blood cultures increase the yield

      • After a positive blood culture, continue to obtain daily blood cultures until two negative cultures in a row are obtained (and patient is afebrile)

    • If patient spikes a fever again during antibiotics course – re-culture!

    • Other labs as appropriate

  • If the patient remains febrile for ≥ 5 days, or with new fever after 5 days of antibiotic therapy, carefully re-evaluate for a source of infection, imaging (i.e. CXR vs. CT of chest/abdomen/ pelvis), ask lab to hold cultures for fungus

    • A consult should be placed to Pediatric Infectious Diseases at this point (if this has not been done already)

    • Discuss anti-fungal treatment strategy with Pediatric Infectious Diseases

    • If evidence of fungal infection is found patient needs complete evaluation including: optho exam, echocardiogram, and renal/liver/spleen ultrasound

  • Colony-Stimulating Factors

    • Attending-dependent on whether to use G-CSF:

      • There is sparse evidence that it reduces mortality in febrile neutropenia

      • There is evidence that starting G-CSF prior to onset of neutropenia significantly shortens the duration of neutropenia, sometimes the depth of the nadir, and the duration of admission for febrile neutropenia

      • Do not use in patients with myelogenous leukemia

  • Prophylaxis

    • Continue patient’s home Pneumocystis jirovecii pneumonia prophylaxis

  • General care

    • Fluids:

      • Make sure that patient is hydrated – if patient has mucositis they may not be drinking

    • Transfusions: Patients who have undergone chemotherapy will often require blood products:

      • pRBC for anemia PRN. (Make sure to order as “leukocyte-free, irradiated” and “CMV safe” if patient is CMV negative or if their CMV status is unknown)

      • Platelets for thrombocytopenia PRN (Typically not until <10k unless patient is symptomatic)

 

Discharge

  • Conditions for discharge (all must be met)

    • Afebrile for >24 hrs

    • Cultures have been negative for > 48 hrs

    • ANC has increased for two days in a row, is presently approaching or >500, and is continuing to increase

  • If all the above conditions are met → can stop IV antibiotics and send patient home with close follow up.

  • If patient has been afebrile for >24 hours, cultures are negative for >48 hours but neutropenia is not resolving (ANC < 500 and not increasing) → continue IV antibiotics until ANC is > 500.

    • If becomes febrile again treat as original febrile with neutropenia with higher suspicion of index for fungal infection.

  • If a patient was on multi-drug therapy and no source was identified, and neutropenia is resolving (ANC > 500, rising) → consider removing antibiotics once patient is afebrile for 24-48 hours and appears clinically well (unless the patient is in the midst of a specified duration of antibiotic therapy; in which case the recommended treatment course should be completed).

  • If a culture is positive and the patient is clinically stable and neutropenia is resolving (ANC > 500, rising) → may be safe to discharge patient home to continue antibiotic therapy (through indwelling catheter) with close follow up.

 

Remember – these are general guidelines (adapted from 2002 IDSA Fever and Neutropenia guidelines). Each patient must be evaluated individually and the decision tree depends both on lab values and the clinical situation.

 

References

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. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 52, 56-93.

DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 903015, Febrile neutropenia; [updated 2016 Nov 02, cited Montefiore Medical Center July 24, 2017]; [about 35 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=903015. Registration and login required.

Engorn, Branden, Flerlage, Jamie, eds. The Harriet Lane Handbook 20th edition. Philadelphia, Elsevier Saunders, 2014: 531-533

Ahmed NM & Flynn PM. Fever in children with chemotherapy-induced neutropenia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on July 24, 2017.)