Term
|
Definition
2 components:
leukocytes: total number of WBCs
differential: percentage of each type of leukocyte
an increase in the percentage of one type of leukocyte means a decrease in the percentage of another
neutrophils and lymphocytes make up 75-90% of the total leukocytes |
|
|
Term
|
Definition
leukocytosis (WBC count > 10,000)
infection
inflammation
tissue necrosis
leukemic neoplasia
leukopenia (WBC count < 4000)
bone marrow failure
antineoplastic chemotherapy or radiation therapy
marrow infiltrative diseases
overwhelming infections
dietary deficiencies
autoimmune diseases |
|
|
Term
how do you calculate ANC?
KNOW HOW TO DO THIS FOR THE EXAM |
|
Definition
ANC = absolute neutrophil count
ANC = total WBC count x percentage of neutrophils
neutrophils = segs + bands
example:
WBC = 4 (x 10^3)
segs = 20% and bands = 5%
ANC = 4000 x (0.2 + 0.05) = 4000 x 0.25 = 1000 |
|
|
Term
what is neutropenia?
KNOW THIS FOR THE EXAM |
|
Definition
ANC < 500 cells/mm^3
ANC expected to decrease to < 500 cells/mm^3 during the next 48 hours
profound neutropenia:
ANC < 100 cells/mm^3 |
|
|
Term
what is fever?
KNOW THIS FOR THE EXAM |
|
Definition
a single oral temp 38.3C (101F) or above
OR
a temp 38C (100.4F) or above for 1 hour or longer |
|
|
Term
|
Definition
major reason for hospitalization during or after chemotherapy
difficult to evaluate due to diminished immune response
FEVER is the hallmark response to infection |
|
|
Term
| clinical features of neutropenic host |
|
Definition
clinically documented infections occur in 20-30% of febrile episodes
bacteremia occurs in 10-25% of all patients, with most episodes occurring with prolonged or profound neutropenia (ANC < 100 cells/mm^3)
fungi may cause:
secondary infection in patients who have received courses of broad spectrum antibiotics
primary infection
primary sites of infection:
alimentary tract - chemo-induced mucosal damage allows invasion of opportunistic organisms
integument - damage by invasive procedure often provides portals of entry for infectious organisms |
|
|
Term
| diagnosis of neutropenic fever |
|
Definition
physical exam: peridontium, pharynx, lower esophagus, lung, perineum, including the anus, eye (fundus), skin, including bone marrow aspirate sites, vascular catheter access sites, tissue around nails
blood culture: bacteria and fungi, central and peripheral
CBC, SCr, BUN, transaminases
urine culture*
CSF*
chest X-ray*
skin lesion aspiration and biopsy*
*consider is s/s of infection at this site is suspected |
|
|
Term
| common sites of infection |
|
Definition
oropharyngeal: periodontal, mucosa, pharynx
lung
skin and soft tissue
sinuses
GI tract
perirectal
catheter sites
bacteremia |
|
|
Term
current common bacterial pathogens in neutropenic patients
KNOW THESE FOR THE EXAM |
|
Definition
GRAM POSITIVE
coagulase (-) staphylococci
Staphylococcus aureus, including MRSA
Enterococcus species, including VRE
Viridan group streptococci
Streptococcus pneumoniae
Streptococcus pyogenes
GRAM NEGATIVE
SPACE KE
Stenotrophomonas malophilia
Pseudomonas aeruginosa
Acinetobacter species
Citrobacter species
Enterobacter species
Klebsiella pneumoniae
Escherichia coli |
|
|
Term
| drug resistant gram negatives causing an increased number of infections |
|
Definition
ESBL genes - broad range of beta-lactam antibiotic resistance:
Kelbsiella species
E. coli strains
carbapenemase-producing strains:
Klebsiella species
P. aeruginosa |
|
|
Term
|
Definition
typically encountered after at least 1 week of prolonged neutropenia and empiric antibiotics
yeasts (Candida species):
superficial infections of mucosa (thrush)
bacteremia secondary to mucositis
deep tissue candidiasis is rare
molds (Aspergillus species):
MOST LIKELY TO CAUSE LIFE-THREATENING INFECTION OF THE SINUSES AND LUNGS
TYPICALLY DEVELOP AFTER 2 WEEKS OR MORE OF NEUTROPENIA |
|
|
Term
| infections in oncology patients |
|
Definition
leading cause of death in neutropenic patients
chemotherapy causes bone marrow suppression:
neutrophils begin to decline at day 3-5
nadir reached around day 7-14
recovery around day 21-28
tumor invasion of bone marrow -> neutropenia
leukemias and lymphomas can cause humoral and cellular defects |
|
|
Term
risk assessment
KNOW WHO HAS TO GET ADMITTED AND STARTED ON IV EMPIRIC THERAPY AND WHO DOESN'T |
|
Definition
HIGH RISK
anticipated prolonged (>7 days duration) and profoun neutropenia (ANC < 100 cells/mm^3)
and/or
significant co-morbid conditions such as: hypotension, pneumonia, new-onset abdominal pain, neurologic changes
MASCC score < 21
ADMIT TO HOSPITAL FOR EMPIRICAL THERAPY
LOW RISK
anticipated brief (< or equal to 7 days duration) neutropenic period
no/few co-morbidities
MASCC score > or equal to 21
OUTPATIENT AND/OR ORAL EMPIRICAL THERAPY |
|
|
Term
the multinational association for supportive care in cancer risk index score (MASCC)
DO NOT MEMORIZE
be aware of things that would be low risk |
|
Definition
burden of febrile neutropenia with no or mild symptoms = 5
no hypotension (systolic BP > 90 mmHg) = 5
no chronic obstructive pulmonary disease = 4
solid tumor or hematologic malignancy with no previous fungal infection = 4
no dehydration requiring parenteral fluids = 3
burden of febrile neutropoenia with moderate symptoms = 3
outpatient status = 3
age < 60 years = 2 |
|
|
Term
| initial antibiotic therapy |
|
Definition
empiric antibiotic therapy should be administered promptly to all neutropenic patients with fever OR s/s of infection
things to consider when choosing antibiotics:
bacteria type, frequency of occurrence, antibiotic susceptibility
drug allergies
organ dysfunction |
|
|
Term
| high risk empiric antibiotics |
|
Definition
General patient = anti-psudomonal beta lactam (cefepime, meropenem, imipenem-cilastatin, or pipercillin-tazobactam)
Suspected catheter related infection, skin/soft tissue infection, pneumonia, or hemodynamic instability: ADD vancomycin
previous infection or colonization with MRSA: ADD vancomycin, linezolid, or daptomycin
Previous infection or colonized with VRE: ADD linezolid or daptomycin
Previous infection or colonization with ESBLs (extended spectrum beta lactamases): carbapenem
Previous infection or colonization with KPC (klebsiella pneumoniae carbapenemase): polymyxin-colistin or tigecycline |
|
|
Term
| low risk empiric antibiotics |
|
Definition
initial PO/IV doses should be administered in clinic or hospital setting
transition to outpatient PO or IV if:
vigilant observation and prompt access to appropriate medical care can be ensured 24 hours a day
preferably located within 1 hour of medical facility; patients that develop recurrent fever or new signs of infection must be admitted and empiric IV antibiotics initiated
patients receiving fluoroquinolone prophylaxis should receive a beta lactam agent for febrile neutropenia episodes |
|
|
Term
| low risk febrile neutropenia |
|
Definition
oral regimen if able to tolerate and absorb
availability of caregiver, telephone, transportation
patient and physician decision
adult regimen: amoxicillin/clavulanate + ciprofloxacin |
|
|
Term
| day 2-3 after empirical antibiotic therapy... |
|
Definition
LOW RISK with unexplained fever -> persistent fever, clinically unstable -> hospitalize (if outpatient) for broad spectrum IV antibiotics -> modify antibiotics according to culture results and/or infection site -> continue antibiotics for 7-14 day course as appropriate for documented infection or longer, i.e. until ANC > 500 and rising
LOW RISK and unexplained fever -> fever is going away, cultures negative -> continue oral or IV antibiotics until ANC > 500 and rising
LOW RISK and documented infection -> modify antibiotics according to culture results and/or infection site -> if responding continue antibiotic for 7-14 day course as appropriate for documented infection, or longer, i.e. until ANC > 500 and rising; if not responding examine and re-image (CT, MRI) for new or worsening sites of infection, culture/biopsy/drain sites of worsening infection; assess for bacterial, viral, and fungal pathogens, review antibiotic coverage for adequacy of dosing and spectrum, consider adding empirical antifungal therapy, broaden antimicrobial coverage for hemodynamic instability
HIGH RISK and documented infection -> as above for LOW RISK and documented infection
HIGH RISK and unexplained fever -> persistent fever, stable clinically -> no changes in empirical antibiotics, assess for infection sites
HIGH RISK and unexplained fever -> fever is going away, cultures negative -> continue antibiotics until ANC > 500 and rising -> recurrent fever during persistent neutropenia |
|
|
Term
|
Definition
fluoroquinolone prophylaxis should be considered for high-risk patients with expected durations of prolonged and profound neutropenia
levofloxacin - preferred when there is an increased risk of mucositis related invasive viridans group streptococcal infection
ciprofloxacin |
|
|
Term
| empirical antifungal therapy |
|
Definition
empirical antifungal therapy and investigation for invasive fungal infections should be considered for patients with persistent or recurrent fever after 4-7 days of antibiotics and whose overall duration of neutropenia is expected to be > 7 days
low risk patients - risk of fungal infection is low and empiric antifungals are not recommended |
|
|
Term
| high risk patient with prolonged (>4 days) fever |
|
Definition
daily examination and history, blood cultures - repeat on limited basis, cultures for any suspected sites of infection
unexplained fever -> clinically stable, rising ANC: myeloid recovery imminent -> no antimicrobial changes unless clinical, microbiologic, or radiographic data suggest new infection
unexplained fever -> clinically stable, myeloid recovery not imminent, consider CT scan sinuses and lungs -> receiving fluconazole (anti-yeast) prophylaxis -> pre-emptive approach - start antifungal based upon results of CT scans chest/sinuses, serial serum galactomannan tests OR empirical antifungal therapy with anti-mold coverage: echinocandin, voriconazole, amphotericin B preparation
unexplained fever -> clinically stable, myeloid recovery not imminent, consider CT scan sinuses and lungs -> receiving anti-mold prophylaxis -> empirical antifungal therapy - consider switch to a different class of mold active antifungal
documented infection -> clinically unstable, worsening signs and symptoms of infection -> examine and re-image (CT, MRI) for new or worsening sites of infection, culture/biopsy/drain sites of worsening infection, assess for bacterial, viral, and fungal pathogens, review antibiotic coverage for adequacy of dosing and spectrum, consider adding empirical antifungal therapy, broaden antimicrobial coverage for hemodynamic instability
galactomannan test is testing for aspergillus
echinocandin = caspofugin, micofugin |
|
|
Term
|
Definition
high risk
Candida:
recommended in patient groups in whom the risk of invasive candidal infections is substantial: HSCT (stem cell transplant) recipients, intensive remission-induction or salvage chemotherapy
fluconazole, itraconazole, voriconazole, posaconazole, micafugin, caspofungin
micafungin and caspofungin are IV only
Aspergillus:
patients 13 years and older undergoing intensive chemo for AML/MDS
allogeneic or autologous transplant recipients if: patients with prior invasive aspergillosis, anticipated prolonged neutropenia periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT
itraconazole, voriconazole, posaconazole
itraconazole and posaconazole are PO only |
|
|
Term
|
Definition
acyclovir prophylaxis:
HSV+ patients undergoing allogeneic HSCT or leukemia induction therapy
acyclovir treatment:
HSV or VZV active infection
yearly inactivated influenza vaccine for all |
|
|
