Immunocompromised Hosts (Kays) Flashcards
Define “neutropenia”.
abnormal reduction in the number of neutrophils circulating in peripheral blood
What ANC count qualifies as neutropenic?
< 1000/mm3
How do you calculate ANC?
ANC = WBC x (% polys + % bands)
There is a high risk of infection in patients with ANC < ______ cells/mm3
500
Risk of infection and death are greatest in patients with ANC < ____ cells/mm3.
100
Patients with severe neutropenia for more than _________ days are at high risk for serious infections.
7-10
What bacteria are most common in neutropenia?
- S. aureus
- S. epidermidis
- streptococci
- enterococci
- E. coli
- K. pneumoniae
- P. aeruginosa
What fungi are most common in neutropenia?
- Candida
- Aspergillus
- Zygomycetes (Mucor, Rhizopus)
What virus is most common in neutropenia?
herpes simplex virus (HSV)
Defects in T-lymphocyte and macrophage function are related to what type of immunity?
cell-mediated immunity
What type of immunity is negatively impacted by underlying disease (Hodgkin’s lymphoma) or immunosuppressive drug therapy in transplant patients?
cell-mediated immunity
Defects in T-lymphocyte and macrophage function result in reduced ability of the host to defend against ____________ pathogens.
intracellular
What bacterial pathogens are implicated in defects in T-lymphocyte and macrophage function (cell-mediated immunity)?
- Listeria
- Nocardia
- Legionella
- Mycobacteria
What fungal pathogens are implicated in defects in T-lymphocyte and macrophage function (cell-mediated immunity)?
- C. neoformans
- Candida
- Histoplasma capsulatum
What viral pathogens are implicated in defects in T-lymphocyte and macrophage function (cell-mediated immunity)?
- CMV
- VZV
- HSV
What protozoal pathogen is implicated in defects in T-lymphocyte and macrophage function (cell-mediated immunity)?
Pneumocystis jiroveci
Defects in B-cell function are related to what type of immunity?
humoral immunity
Underlying disease (multiple myeloma, chronic lymphocytic leukemia), splenectomy, and immunosuppressive therapies (steroids, chemotherapy) can all lead to which defects?
defects in B-cell function (humoral immunity)
What bacterial pathogens (encapsulated) are implicated in defects in B-cell function (humoral immunity)?
- S. pneumoniae
- H. influenzae
- N. meningitidis
What pathogens are implicated in destruction of the skin as a protective barrier?
- S. aureus
- S. epidermidis
- Candida species
What bacterial pathogens are implicated in the destruction of mucus membranes of the oropharynx and GI tract as protective barriers?
- S. aureus
- S. epidermidis
- Enterobacteriaceae
- streptococci
- P. aeruginosa
- Bacteroides species
What fungal pathogens are implicated in the destruction of mucus membranes of the oropharynx and GI tract as protective barriers?
Candida species
What viral pathogen is implicated in the destruction of mucus membranes of the oropharynx and GI tract as protective barriers?
HSV
What bacterial pathogens are implicated in solid organ transplant?
- S. aureus
- S. epidermidis
- Enterobacteriaceae
- P. aeruginosa
- Bacteroides species
What fungal pathogens are implicated in solid organ transplant?
Candida species
What viral pathogen is implicated in solid organ transplant?
HSV
What is the most common colonization site for infection in cancer patients?
GI tract
Bacteremias are caused predominantly by normal gut flora, and develop as a result of ____________________________.
microbial translocation across injured GI mucosa
Oropharyngeal flora rapidly change to primarily ______________ in hospitalized patients.
Gram-negative bacilli
Febrile episodes in neutropenic cancer patients are attributed to _____________ documented infection in only 30-40% of cases.
microbiologically
45-70% of bacteremic episodes in cancer patients are due to ______________.
Gram-positive cocci
Why are 45-70% of bacteremic episodes in cancer patients are due to gram-positive cocci?
- use of indwelling central/peripheral IV catheters
- use of broad spectrum antibiotics with poor gram-positive activity
- higher rates of mucositis caused by aggressive cancer treatments
- prophylaxis with Bactrim or fluoroquinolones
What is the primary risk factor for invasive aspergillosis?
prolonged neutropenia
Invasive Aspergillus infection is seen primarily in patients with ______________ and undergoing ________________.
hematologic malignancies; HSCT
Aspergillus is acquired by inhalation of airborne _______.
spores
What is the most important clinical finding of infection in neutropenic cancer patients?
fever
In order for a neutropenic cancer patient to be considered low-risk for infection, what criteria must be met?
- neutropenia for 7 days or less
- no/few comorbidities
- clinically stable at onset of fever
- no identified focus of infection or simple infection (e.g., UTI)
In order for a neutropenic cancer patient to be considered high-risk for infection, what criteria must be met?
profound (ANC ≤ 100 cells/mm3 ) AND prolonged neutropenia (> 7 days) and/or significant commodities (hypotension, pneumonia, new-onset abdominal pain, neurologic changes)
What regimen should be given for initial management of febrile neutropenia in low-risk patients with adequate outpatient infrastructure who are candidates for an oral regimen?
oral FQ + Augmentin
What regimen should be given for initial management of febrile neutropenia in low-risk patients with inadequate outpatient infrastructure who are not candidates for an oral regimen?
Inpatient IV antibiotics (monotherapy)
- Zosyn
- antispeudomonal carbapenem
- cefepime
- ceftazidime
What regimen should be given for initial management of febrile neutropenia in high-risk patients?
Inpatient IV antibiotics (monotherapy)
- Zosyn
- pseudomonal carbaoenem
- cefepime
- ceftazidime
What should be added to initial febrile neutropenia treatment in high-risk patients with cellulitis, pneumonia, severe sepsis/shock, gram-positive bacteremia, suspected IV catheter infection, known MRSA colonization, or resistant streptococci?
IV vancomycin
What should be added to initial febrile neutropenia treatment in high-risk patients with septic shock, gram-negative bacteremia, or pneumonia?
aminoglycoside or antipseudonomal fluoroquinolone
What are the options for beta-lactam monotherapy as an empiric antibiotic regimen for febrile neutropenia?
- ceftazidime 2 g q8h
- cefepime 2 g q8h
- Zosyn 4.5 g q6h
- imipenem 500 mg q6h
- meropenem 1 g q8h
Does the IDSA recommend vancomycin or other gram-positive agents as a standard part of the initial antibiotic regimen for febrile neutropenia?
no
What are some situations that would warrant the addition of gram-positive agents to an empiric regimen for febrile neutropenia?
- hemodynamic instability/other evidence of severe sepsis
- radiographically documented pneumonia
- positive blood cultures for gram-positive pathogen before final identification and susceptibility test results are known
- clinically suspected serious catheter-related infection (e.g. cellulitis around the catheter entry/exit site)
- skin/soft tissue infection at any site
- colonization with MRSA, VRE, or PRSP
- severe mucositis (if FQ prophylaxis has been given or if ceftazidime used as empiric therapy)
What is the preferred empiric regimen for febrile neutropenia in penicillin-allergic patients?
ciprofloxacin + aztreonam + vancomycin
In febrile neutropenia, we should re-evaluate the clinical status of the patient after _________ of empiric antimicrobial therapy.
48-72 hrs
What therapy additions can be considered if a febrile neutropenia patient is found to have MRSA after empiric therapy?
- vancomycin
- linezolid
- daptomycin
What therapy additions can be considered if a febrile neutropenia patient is found to have VRE after initiation of empiric therapy?
- linezolid
- daptomycin
What therapy additions can be considered if a febrile neutropenia patient is found to have an ESBL producer after initiation of empiric therapy?
carbapenem
What therapy additions can be considered if a febrile neutropenia patient is found to have a KPC producer after initiation of empiric therapy?
- ceftazidime/avibactam
- meropenem/vaborbactam
- imipenem/cilastatin/relebactam
In febrile neutropenia, persistence of fever or development of new fever during broad-spectrum antibacterial therapy may indicate the presence of a __________ infection.
fungal
What two viruses should be evaluated in neutropenic patients with vesicular or ulcerative skin or mucosal lesions?
HSV or VZV
What drug should be initiated if a neutropenic patient is found to have HSV/VZV?
acyclovir
What drug should be initiated in a neutropenic patient found to have CMV?
ganciclovir
What is the most important determinant of patient outcomes in febrile neutropenia?
resolution of neutropenia
Annual influenza vaccination with _________ vaccine is recommended for all neutropenic patients.
inactivated
