Exam 5 lecture 2 (pt 1) Flashcards
what are some risk factors for infection in immunocompromised host
Neutropenia
Immune system defects
Destruction of protective barriers
environmental contamination/alternation of microbial flora
What ANC is neutropenia?
less than 1000 cells
high risk<500
Higest risk<100
What are the two types of immune system defects
Defects in cell mediated immunity
Defects in humoral immunity
Link between duration and rapidity of decline and risk for patient
Increased rapidity and duration leads to increased risk
Highest risk patients have neutropenia lasting how long
7-10 days
What are common bacterial pathogens seen in infections seen in immunocompromise dhosts
S aureus
enterobacterales
pseudomonas aeruginosa (top 3 highest fatality)
S. epidermidis
Streptococci
Enterococcus
what are fungi seen in immune compromise dpatients
Candida
Aspergilis
Zygomycetes
What are viruses seen in immune compromised patients
HSV
VZV
CMV
What are cell mediated immuntity (cells involved and intra/extracellular)
T lymphocytes
Primary defense against intracellular pathogens
What is humoral immuntity (cells involved and intra/extracellular)
B lymphocytes
Primary defense against extracellular pathogens
defects in T lymphocyte and macrophage function relay on 2 things
Underlying disease (hodgkins lymphoma)
Immunosuppressive drugs (tacrolimus and sarolimus, steroids)
Defects in B lymphocyte function and macrophage function relay on 2 things
Underlying disease (MM, CLL, splenectomy)
Immunosuppressive drugs
Common pathogens seen in skin destruction of protective barriers
- Venipuncture/lines
- Common pathogens
-S. Aureus
- S. Epidermis
- Candida spp
What are common pathogens seen in mucous membranes
chemotherapy, radiation
Common pathogens
bacteria
- s. aureus
- s epidermis
- streptococci
- enterobacterales
- P. aeruginosa
- Bacteroides spp
Fungi
- candida spp
Virus
-HSV
compare pathogens seen in mucous membranes and surgery
same except no streptococci in surgery
what happens to oropharyngeal flora in hospitalized pts
They rapidly change to gram negative bacilli in hospitalized pts
What is the number 1 cause of death in neutropenic cancer pts
Infection
profound neutropenia (ANC<500)= greatest risk of infection
febrile episodes are attributed to microbiologically documented infection how often
30-40%
(we grow something only 20-40% of the time)
what % of infections in neutropenic cancer patients are gram positive
45-75%
What are gram positive and gram negative bacterial infections seen in neutropenic cancer patients
Gram Positive
staph
- MSSA, MRSA
Viridians strep
- mucositis
Gram negative
Enterobacterales
- E coli, klebsiella spp
P. Aeruginosa
- high morbidity and mortality
What type of fungal infections do we see with neutropenic cancer patients
- Candida spp (60%)
- aspergillus spp
WHo is at highest risk for invasive fungal infections
Prolonged neutropenia + broad spectrum antibiotics and/or steroids
who is at risk for aspergillus spp
Heme and HSCT patients- prolonged neutropenia
What are other infections that attack neutropenic cancer patients
viruses
- HSV
Protozoan
- Pneumocystitis jirovecci (PJP)
- toxoplasma gondii
- TMP/SMX
How is toxoplasma gondii and PJP avoided
TMP/SMX prophylaxis
What is the most important finding in diagnosing infections in neutropenic cancer pts
Fever
other s/s absent due to neutropenia
What are labs and diagnostics used in diagnosing infections in neutropenic cancer patients
Labs
- blood culture
- CBC with differential
- BMP or CMP
Diagnostics
- imaging
- aspiration or biopsy
For infection risk assessment of febrile neutropenia, what are low risk and high risk patients
low- neutropenia <7 days, clinically stable, inpatient or outpatient, IV and/or PO
High- ANC <100 and neutropenia >7 days, clinically unstable, inpatient, IV therapy
What coverage should management of febrile neutropenia include
Antipseudomonal coverage
How to treat low risk febrile neutropenia (define low risk too)
Low risk- ANticipated neutropenia < 7 days, clinically stable and no medical comorbidities and outpatient at fever onset
MASCC score > or = 21
If they meet criteria for outpatient
Oral FQ + amox/clav
If they do NOT meet criteria for outpatient use IV therapy
piperacillin/tazobactam, cefepime, ceftazidine
how to treat high risk febrile neutropenia
Inpatient IV antibiotics
- piperacillin tazobactam, cefepime, ceftazidime
Add IV vancomycin for cellulitis, pneumonia, severe sepsis or shock or MRSA
Empiric therapy of febrile neutropenia
B lactam monotherapy
- Cefepime or piperacillin/tazo are most common
imipenem, Meropenem and ceftazidime may be used aswell
mono vs combination for management of febrile neutropenia
Comparable efficacy to combination regimens. Mono is better.
disadvantage of ceftazidime use in febrile neutropenia
No gram positive coverage so it might lead to selection of resistant organisms.
Is vancomycin recommended in initial empiric regimen for febrile neutropenia
NOT recommended as initial therapy
criteria for vanc addition for febrile neutropenia
- hemodynamically unstable (septic shock)
- pneumonia
- blood cultures frowing gram positive bacteria
- Line/port infection
- SSTI
-Severe mucositis - Colonization with resistant gram positive bacteria
what do we do for penicillin allergy patients for febrile neutropenia
Avoid B lactams
Use combo of cipro +aztreonam + vanc
oral regimens to give to outpatients low risk febrile neutropenia
cipro + amox clav (most common)
levofloxacin
ciprofloxacin + clindamycin
Compare efficacy oral antibiotics to IV for low risk febrile neutropenia. WHat are requirements to be on oral antibiotic therapy
comparable efficacy to IV
Not to be used in pts already on FQ prophylaxis. Requires patient compliance and 24 hr access to medical care if instability develops
Targeted therapy for febrile neutropenia for MRSA, VRE, ESBL, KPC, NDM/IMP/VIM
MRSA- Vancomycin
VRE- daptomycin or linezolid
Extended spectrum beta lactamases- Carbapenem
KPC (carbapenem resistant) (a- meropenem/vabrobactam, imipenem/cilastatin/relebactam, ceftazidime/avibactam
NDM/IMP/VIM- cefiderocol
- What to do for febrile neutropenia if low risk patient in outpatient continues to have fever?
What to do if they are responding? Not responsing? - What to do for febrile neutropenia patient (high or low risk) that defervesced and are clinically stable?
- admit to hospital and place on IV. If they respond treat 7-14 days as indicated by type/site of infection and until ANC>500 and rising
If not reponding, modify/broaden by adding vancomycin and/or additional gram negative coverage. Consider antifungal. - Continue oral or IV antibiotics until ANC>500 and rising
WHen do we consider adding fungal therapy for management of febrile neutropenia
Patients with persistent fever or develop new fever with undocumented infection after 4-7 days.
We can only isolate fungal infection from a person with fungus <50% of the time
What are treatment options for fungal treatment of febrile neutropenia? Duration?
Amphotericin B deoxycholate or liposomal amphotericin B
Azoles (flucanozole, voriconazole, posaconazole, isavuconazole)
Echinocandins
(micafungin, caspofungin, anidulafungin
Continue therapy for 2 wks in absence of s/s of fungal infenction
When do we use antiviral therapy for management of febrile neutropenia? What drugs to use
Vesicular/ulcerative skin or mucosal lesions, evaluate for HSV. Initiate Acyclovir, valacyclovir in HSV and ganciclovir/valganciclovir in CMV
most common pathogens seen in catheter related blood stream infections? What are indications for catheter removal?
S. aureus and S. epidermis are most common
Indications
- SQ tunnel infection
- Failure to clear blood cultures after 72 hrs of sppropriate microbial therapy
- persistent fever
- Septic emboli
Wat are pathogens that we need to remove catheter for?
Fungi
Mycobacteria
P. aeruginosa
Bacillus spp
C. jeikeium
What is the most important determinant of patient outcomes for management of febrile neutropenia
Resulotion of neutropenia (faster we get them not to be neutropeniz the better outcome will be)
When do we use CSF? Name the drugs
May be useful in pts with ANC<500, uncontrolled primary disease, PNA, IFI (invasive fungal infection), hypotension, sepsis, multiorgan dysfunction with prolonged neutropenia who are NOT REPOSNDING to antimicrobial therapy
Advantage/disadvantage of CSF in pts
-decreased duration/severity of neutropenia
- decreased duration of antimicrobial therapy
- decreased hospitalization and reduced hospitalization stay
but
No benefit in mortality
WHat are two big aspects of prophylaxis for febrile neutropenia pts
Infection control (IC)- laminar flow rooms
Patient population (who gets prophylaxis)- Moderate-high risk pts with expected ANC<100 for >7 days, Heme malignancy patients (AML, MM, Lymphoma, CLL), stem cell transplant pts, GVHD with high dose steroids, use of alemtuzumab
What to use as prophylaxis for febrile neutropenia pts
fluoroqinalone prophylaxis
(Cipro or levo)
If we have breakthrough infection of fluoroquinalone prophylaxis, do we use FQ in empiric therapy?
no
When to use antifungal prophylaxis
Allogenic HSCT
Intensive induction chemo for acute leukemia
Azoles
Echinocandina
AML, MDS, GVHD on high dose steroids
When to use antiviral prophylaxis for febrile neutropenia pts
Annual inactivated influenza vaccine recommended for all pts
HSV seropositive pts undergoing allogenic HSCT or leukemia induction therapy
Varicella vaccine may be useful in seronegative adults
When to use TMP SMX as prophylaxis in febrile neutropenia pts
Allogenic HSCT and GVHD on high dose steroids
Substantially reduces risk of PJP pneumonia
