Neutropenic Fever

Question 1

Neutropenic fever arises in cancer pts taking chemotherapeutrics that induce _____ and reduce the developmental integrity of the _______

Answer 1

Myelosuppression; GI mucosa

[myelosuppression can lead to a muted and blunted neutrophil-mediated inflammatory response, therefore a fever is the earliest (and maybe the only) sign of infection]

Question 2

Define neutropenic fever

Answer 2

Temp above 38.5 C (101.4 F) with an absolute neutrophil count (ANC) below 500 cells/microliter

Question 3

Neutropenic fever constitutes a medical emergency with a 100% mortality rate if not treated for 3 days. 99% of the infectious agents involved with neutropenic fever are normal, endogenous flora. What are some of the most common infectious agents associated with indwelling central venous catheters?

Answer 3

S.aureus
S.epidermidis
Klebsiella spp.

Question 4

What are some of the fungal infections associated with neutropenic fever?

Answer 4

Candida (most common)

Aspergillus and other fungi may be involved

Pneumocystis and toxoplasma can cause fever but are relatively unusual

Question 5

What type of physical exam should be avoided if the ANC is <500 cells/microliter

Answer 5

Rectal exam

Microscopic tears occur during rectal exams, allowing a potal for bacteria to enter the body — potentially leads to fulminant sepsis and death w/i 24 hours

[also consider avoiding gynecologic exam in females]

Question 6

Primary prophylaxis involves administration of antimicrobial drugs to prevent infection in pts at increased risk. What defines a pt as high risk?

Answer 6

Those who are expected to be neutropenic (<500 cells/microliter) for > 7 days

Question 7

Antibiotics used for primary prophylaxis in high risk pts target P.aeruginosa and other gram negative bacilli. What class is typically used?

Answer 7

Fluoroquinolones — levofloxacin, ciprofloxacin

Question 8

Cautions with fluoroquinolone use

Answer 8

Prolonged QT interval
Tendon rupture
Promotion of abx resistance
Increased risk for C.diff

Question 9

What antifungal is used for primary prophylaxis in high risk pts and why?

Answer 9

Fluconazole — primarily targets candida

Advantages to fluconazole — oral and IV formulations, good tolerability, inexpensive generic, less drug-drug interactions vs. other extended spectrum azoles

Question 10

Cautions to fluconazole use

Answer 10

Narrower spectrum for candida spp.

Fluconazole resistance

No activity against Aspergillus spp.

Question 11

While fluconazole is the antifungal of choice for primary prophylaxis, what alternative drug class may be used d/t its broader spectrum of coverage and good safety profile?

Answer 11

Echinocandins — caspofungin, micafungin, anidulafungin

[cautions = IV only, higher cost]

Question 12

Secondary prophylaxis is utilized to prevent recurrent infection, usually in pts with hx of prior fungal infection. What drug is given in this case?

Answer 12

Voriconazole

Question 13

Voriconazole is a first-line agent for _______

It cannot be given together with certain chemotherapeutics like _____ or ______. Severe neurotoxicity occurs if Voriconazole is given with chemotherapeutic ________.

Answer 13

Aspergillus spp.

Cytarabine; fludarabine; vincristine

Question 14

Since voriconazole cannot be given together with some chemotherapeutics, one strategy is to suspend it 1 week prior to chemotherapy and to start it again after the dosing regimen.

To continue an antifungal during chemotherapy, _______ or an _______ can be used

Answer 14

Amphotericin B; echinocandin

Question 15

Empiric therapy is utilized when a suspected neutropenic fever is occurring. What is the general management strategy in this case?

Answer 15

IV abx given until ANC is above 1000 cells/mL

After this is achieved, a switch to oral abx is possible (ONLY if pt is afebrile and tolerating meals w/o emesis)

Combination IV regimens are preferred to single agents

Question 16

Inpatient empiric IV abx options that may be given to high risk pts with suspected neutropenic fever

Answer 16

Piperacillin + tazobactam

A carbapenem (imipenem, meropenem, doripenem, ertapenem)

Ceftazidime

Cefepime

[Notes: piperacillin active against P.aeruginosa, tazobactam is a beta lactamase inhibitor, carbapenems active against gram negative and gram positive, ceftazidime is a 3rd gen cephalosporin w/ gram negative coverage; cefepime has gram negative, gram positive, and P.aeruginosa coverage]

Question 17

Empiric IV abx for suspected neutropenic fever may be adjusted based off specific clinical data.

Name drug(s) of choice for cellulitis or PNA

Answer 17

Vancomycin

Linezolid

Question 18

Empiric IV abx for suspected neutropenic fever may be adjusted based off specific clinical data.

Name drug(s) of choice for gram negative bacteremia

Answer 18

Add an aminoglycoside (i.e., gentamycin)

Question 19

Empiric IV abx for suspected neutropenic fever may be adjusted based off specific clinical data.

Name drug(s) of choice for abdominal symptoms or suspected C.diff

Answer 19

Metronidazole

Question 20

Outpatient oral regimens given in low risk pts

Answer 20

Ciprofloxacin + amoxicillin/clavulanic acid

[clavulanic acid is beta lactamase inhibitor]

Question 21

During empiric abx treatment for neutropenic fever, when should an empiric antifungal be added and what agent is typically used?

Answer 21

Empiric antifungal should be added if persistent or recurrent fever does not resolve after 5 days with abx alone

Caspofungin is agent of choice — active against candida spp.

Question 22

In addition to abx and antifungal therapy for neutropenic fever, what is an important initial step in management that lessens the risk of hypotension and the complication of organ ischemia and damage?

Answer 22

Adequate hydration

Question 23

In addition to adequate hydration, abx, and antifungal therapy, what additional drug may be given to decrease the duration of fever and neutropenia as well as decrease the length of hospitalization?

Answer 23

G-CSF (Filgrastim)