Infections in immunocompromised patients - 4 questions Flashcards
Risk factors for infection
1.Neutropenia
- reduction in number of circulating neutrophils
- absolute neutrophil count less than 1000cells/mm^2
2.Immune system defects
- defects in cell-mediated immunity (primary defense against intracellular pathogens)
- defects in humoral immunity (primary defense against extracellular pathogens)
3.Destruction of protective barriers
- Skin, mucous membranes, surgery
4.Environmental contamination/alteration of microbial flora
- transfer of organisms from patient to patient via health care workers
- contaminated equitment, water, and/or food
- alteration of normal flora in hospital settings
2.Immune system defects
What happens when there is defects in cell mediated immunity
Cell mediated immunity is primary defense against intracellular pathogens
defects in T lymphocytes and macrophage function leads to underlying disease and reduced ability of host to defen against intracellular pathogens
- Fungi: candida, Histoplasma
-Bacteria: legionella, listeria, mycobacteria - Viruses CMV, HSV, VZV
- Protozoal: PJP
2.Immune system defects
What happens when there is defects in humoral immunity
humoral immunity is primary defense against extracellular pathogens
defects in B lymphocytes function leads to underlying disease and reduced ability of host to defen against extracellular pathogens
Bacteria: S. Pneumoniae, H. Influenzae, N. meningitidis
Destruction of protective barriers
pathogens in skin, mucous membranes, and surgery
Skin
- S. aureus, S. epidermidis, Candida
Mucous membrane
- S. aureus, S. epidermidis, Streptococci, P. aeruginosa
Surgery
- S. aureus, S. epidermidis, Enterobacterales, P. aeruginosa
Neutropenia
ANC <1000
High risk for infection with ANC <500
highest risk with ANC <100
the longer the patient is neutropenic and the faster the decline in ANC puts patient at increased risk of infection
Common Pathogens
Bacteria
S. aureus
Enterobacterales
P. aeruginosa
Common Pathogens
Fungi
Candida spp
Aspergillus
Zygomycetes (mucor, Rhizopus)
Common Pathogens
Viruses
Herpes simplex virus
varicella zoster virus
Cytomegalovirus
Infections in neutropenic cancer patients
Patients at greatest risk of infection are those with ANC<500 - Profound neutropenia*** - EXAM Q
Single oral temp > or equal to 101 or oral temp greater than or equal to 100.4 persisting for 1 hour or longer - EXAM Q
Low risk: (neutropenia for 7 days or less)
- Oral FQ+ Augmentin (observe after first dose
-If patient cannot take oral: zosyn and consider step down to PO therapy when appropriate
High risk: (neutropenia for >7 days and ANC < or equal to 100
- Cefepime
- ADD IV vancomycin for cellulitis, pneumonia, severe sepsis or shock
Management of febrile neutropenia
Empiric antimicrobial regimens for low risk in and out patient and for high risk patient
when to add vancomycin?
low risk outpatient:
- Oral FQ and augmentin
Low and high risk inpatient
Cefepime 2g q8h
zosyn 4.5g q6h
Imipenem
Meropenem
ADD vancomycin only if:
- hemodynamic instability/sepsis
- pneumonia
- blood culture grows gram positive bacteria
- line/port infection
- SSTI
- Severe mucositis
- colonization with resistant gram positive bacteria (previous history with MRSA infection)
Management of febrile neutropenia
Empiric regimen for low risk in and out patient and for high risk patient
Allergies and oral regimens
Penicillin allergy:
In patient regimen:
- Ciprofloxacin + aztreonam + vancomycin
Oral antimicrobial regimens for low risk outpatient:
- ciprofloxacin + augmentin
- levofloxacin
- ciprofloxacin + clindamycin
Management of febrile neutropenia
Pathogen directed therapy
MRSA, VRE, ESBL, KPC, NDM/IMP/VIM
MRSA –> Vancomycin
VRE –> daptomycin or linezolid
ESBL –> carbapenems (imipenem or meropenem)
KPC –> meropenem/vaborbactam
NDM/IMP/VIM –> cefiderocol
Management of febrile neutropenia
Antifungal therapy
When to consider adding antifungal coverage?
What should we add
Initation:
-high incidence of fungal infection at autopsy,
-patient with persistent fever or develop new fever with undocumented infection after 4-7 days of empiric regimen ,
TX:
Amphotericin B - covers most yeast and molds
Azoles - Fluconazole
Echinocandins - Micafungin
Continue therapy for 2 weeks in absense of s/sx of IFI (often continued for duration of neutropenia)
Management of febrile neutropenia
Antiviral therapy
When to start
what to start
Start if:
If patient has vesicular/ulcerative or mucosal lesions
presumed or confirmed viral infection
Treatment
HSV/VZV: Acyclovir, valcyclovir
CMV: ganciclovir, valganciclovir
Management of febrile neutropenia
Catheter related bloodstream infection
S aureus and S epidermidis most common
Indication for catheter removal:
subQ tunnel infection,
failure to clear blood cultures after 72 hours of appropriate antimicrobial therapy
persistent fever
septic emboli
if pathogens present: (fungi (typically candida), mycobacteria, p. aeruginosa)
Optimal duration
for SSTI, CLABSI, Pneumonia, sinusitis, UTi, Aspergillus, HSV/VZV, Influenza
usually want to also consider how the patient is responding and making sure they are clinically stable
SSTI: 7-14 days
CLABSI: 2-6 weeks
Pneumonia: 10-21 days
sinusitis: 10 days
UTI: 7-14 days
Aspergillus: 12 weeks
HSV/VZV: 7-10 days
Influenza: 5 days
bacterial Prophylaxis
Who gets prophylaxis
Patient who will get prophylaxis
- moderate and high risk patients with expected ANC < or equal to 100 for >7 days
- Heme malignancies (AML, MM, Lymphoma, CLL)
- Allogeneic and autologous HSCT - cell transplant patients
- Graph vs host patient with high dose steroid
- anyone receiving alemtuzumab for their conditioning therapy
TX:
Ciprofloxacin or levofloxacin
If patients have breakthrough infection on FQ DO not use FQ in empiric therapy TX
Prophylaxis
Who gets antifungal prophylaxis?
What do they get
Who gets it
- Cell transplant patients
- intensive chemo patients for acute leukemia
- AML, MDS, GVHD on high dose steroids
Antifungal prophylaxis:
-Usually AZOLE but if patient has prolonged QTC or liver disease use echinocandins
-For those with AML,MDL,GVHD on high dose steroids will recieve:
- Posaconazole or isavuconazole (need activity against zygomycese
Antiviral Prophylaxis
Who gets it
What do they get
Who gets it:
- Anypatient seropositive for HIV whos undergoing allogenic stem cell transplant or leukemia induction therapy:
-acyclovir
-annual inactivated influenza vaccine FOR ALL PATIENTS
TMP/SMX Prophylaxis
Who gets it
What do they get
Who gets it:
- Allogeneic host stem cell transplant patients and graph verses host disease patients on high dose steroids
(TMP/SMX reduces risk of PJP pneumonia)
Considerations
CSF?
Most important determinant in patients outcome is resolution of neutropenia
We can help with resolving neutropenia by adding colony-stimulating factors: filgrastim and sargrasmostim
Useful in patient with ANC < or equal to 500, uncontrolled disease, sepsis
