Infections of immunocompromised host Flashcards by Meghan Collins

Definition of immunocompromised host

Patient with intrinsic or acquired defects in host immune defenses that predispose to development of infectious complications

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4 major risk factors for infection

Neutropenia
Immune system defects
Destruction of protective skin barrier
Environmental contamination/alteration of microbial flora

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Neutropenia

-Reduction in number of circulating neutrophils
-ANC < 1000 cells/mm3 (HIGH RISK)
-Severity, rate of decline, and duration of neutropenia
**Longer duration = more likely to develop infections

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2 types of immune system defects

Defects in cell-mediated immunity
Defects in humoral immunity

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Destruction of protective barriers

Skin
Mucous membranes
Surgery

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Environmental contamination/alteration of microbial flora

-Transfer of organisms from patient to patient via healthcare workers
-Contaminated equipment, water, and/or food
-Alteration of normal flora in hospital setting

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RF for infection with respect to ANC

-High risk: ANC < 500 cells/mm3
-Highest risk: ANC < 100 cells/mm3
-Increased rapidity of ANC decline
-Increased duration of neutropenia
-Highest risk with severe neutropenia > 7-10 days
**Can happen with cycles of chemo/stem cells

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Common bacterial pathogens

S. aureus
S. epidermidis
Streptococci
Enterococcus spp
Enterobacterales
P. aeruginosa

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Common fungal pathogens

-Candida spp
-Aspergillus (mold)
-Zygomycetes (mucor, rhizopus)

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Common viral pathogens

-Herpes simplex virus (HSV)
-Varicella zoster virus (VZV)
-Cytomegalovirus (CMV)

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Cell-mediated immunity
- ______ lymphocytes
-Primary defense against _____ pathogens

T
Intracellular

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What are the 2 major things that result in defects in T-lymphocyte and macrophage function

Underlying disease: Hodgkins lymphoma
Immunosuppressive drugs: tacrolimus; steroids

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Which pathogens are patients pre-disposed to if they have a defect in cell-mediated immunity?

Bacteria
1. Listeria
2. Nocardia
3. Legionella
4. Mycobacteria

Fungi
1. C. neoformans
2. Candida
3. Histoplasma capsulatum

Virus
1. CMV
2. VZV
3. HSV

Protozoa
1. PJP

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Humoral immunity
-______ lymphocytes
-Primary defense against _____ pathogens

B
Extracellular

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2 major things that result in B-lymphocyte defects

Underlying disease (Multiple myeloma, CLL, splenectomy)
Immunosuppressive drugs (steroids, immunotx, chemotx)

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Which pathogens are pts with humoral immunity defects predisposed to?

Bacteria (encapsulated)
1. S. pneumoniae
2. H. influenzae
3. N. meningitidis

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What causes skin destruction?

Common pathogens these pts will be exposed to

Venipuncture, lines/ports

Bacteria
-S. aureus
-S. epidermidis
-Candida spp.

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What causes mucous membrane destruction?

Common pathogens these pts will be exposed to

Chemotherapy; radiation

Bacteria
-S. aureus
-S. epidermidis
-Streptococci
-Enterobacterales
-P. aeruginosa
-Bacteroides spp.

Fungi
-Candida spp (common GI pathogen; may lead to dissemination)

Virus
-HSV

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Reason for surgery that destroys protective barriers?

Common pathogens these pts will be exposed to

Solid organ transplant patients

Bacteria
-S. aureus
-S. epidermidis
-Enterobacterales
-P. aeruginosa
-Bacteroides spp.

Fungi
-Candida spp

Virus
-HSV

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Common sites of infection for cancer pts

Skin
Oral pharynx
GI tract
Lungs
Sinuses

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Environmental contamination

Pesticides on fruits/veggies
Landfills
Water supply in hospital (may have leak –> mold; outbreak of bacteria in water supply)
No HCP handwashing b/w rooms
Non-sterile scopes

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Alteration of microbial flora
-Oropharyngeal flora rapidly change to primarily ___ in hospitalized pts
-50% of hospitalized cancer pts develop infections ____ admission
-_____ spectrum tx have greatest impact on normal flora
-Common pathogens

Gram (-) flora; within first 48H at hospital, gram (-) bacteria develop which are more resistant and difficult to eradicate

After

Broad

Enterobacterales, P. aeruginosa, S. aureus, Candida, Aspergillus

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____ is leading cause of death in neutropenic cancer pts

Infection

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Profound neutropenia (ANC < ____ cells/mm3) = greatest risk for infection

500

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Febrile episodes attributed to microbiologically documented infection in ____ of cases

Less than half (pts rarely have anything grow, so it is tricky to diagnose)

Bacterial infections common in neutropenic cancer pts

Staph (MSSA, MRSA, CoNS) Viridans strep (mucositis) Enterobacterales (e. coli, klebsiella spp) = gram (-) P. aeruginosa (high morbidity and mortality) = gram (-) Enterococci spp **mainly from gram (+) organisms, but not ones causing life-threatening conditions

Invasive fungal infections in neutropenic cancer pts -Prolonged neutropenia + _______ and/or steroids = highest risk -Candida ______ is most common; up to 60% of cancer pts develop thrush; disseminated infections (damaged mucous membranes --> colonized with candida --> enter ______) **Not easy to grow out in cultures

Broad spectrum Bloodstream

Invasive fungal infections in neutropenic cancer pts Aspergillus spp -Heme and HSCT patients = _____ neutropenia -Inhalation of airborne spores --> lung colonization --> invade lung parenchyma & pulmonary vessels --> hemorrhage and pulmonary infarcts --> ____ -Sinusitis; disseminated disease (____ eating way up to brain)

Prolonged Mortality Mold

HSV in neutropenic cancer pts -Clinical disease in pts with serologic evidence of ____ -Reactivation typically manifests as ___ or ___ infection -May disseminate in rare cases

Prior infection Oral/genital

Protozoan infections in neutropenic cancer pts -Pneumocystis jirovecii (PJP): typically manifests as _____ -Toxoplasma gondii typically manifests _____ -______ has drastically reduced incidence of both of these infections

Severe lung infection Lung, brain, and eye disease Bactrim

Clinical presentation of infection in neutropenic cancer pt

FEVER!!!!! (a lot dont have WBC so cannot mount immune response) -Non-infectious causes: blood products, chemo, drug fever, underlying malignancy

Labs to check for infection

Blood cultures CBC with differential BMP or CMP

Diagnostic for infection

Imaging Aspiration or biopsy

Presentation for low risk febrile neutropenia

Neutropenia NMT 7d Clinically stable Inpt or outpt; IV and/or PO *Low/few comorbidites *UTI/uncomplicated cellulitis

Presentation for high risk febrile neutropenia

ANC < 100 cells/mm3 AND neutropenia > 7d Clinically unstable Inpatient, IV tx *Hypotensive/neurological changes *Patient admitted

Management of febrile neutropenia should include _________ coverage empirically

Antipseudomonal

Tx for low risk febrile neutropenia & candidate for oral regimen

Oral FQ + amox/clav

Tx for low risk febrile neutropenia & not a candidate for oral regimen

Inpatient IV abx (monotherapy) Pip/taz Antipseudomonal Carbapenem Cefepime Ceftazidime

Tx for high risk febrile neutropenic pts

Inpatient IV abx (monotherapy) Pip/taz Antipsuedomonal Carbapenem Cefepim Ceftazidime

When is IV vanc added for febrile neutropenic pts?

NOT recommended as standard part of initial empiric regimen -Hemodynamic instability/sepsis -Pneumonia -Blood cultures growing gram (+) bacteria -Line/port infection -SSTI -Severe mucositis -Colonization with resistant gram-positive bacteria or prior MRSA infection

Empiric antimicrobial regimen for febrile neutropenia

Beta lactam 1. Cefepime 2 g Q8H 2. Pip/taz 4.5 g Q6H Reserved for prior ESBL infection: Imipenem 500 mg Q6H Meropenem 1 g Q8H Ceftazidime (fell out of favor)

Tx of febrile neutropenia in pts with PCN allergy

-Avoid beta lactams, including carbapenems, if hx of immediate type 1 hypersensitivity rxn (hives; anaphylaxis) -Ciprofloxacin + aztreonam + vanc

Considerations for febrile neutropenia tx in pts with PCN allergy **HINT: think about the 3 drugs

-Not to be used in pts already on FQ prophylaxis (bc high risk of resistance) -Requires pt compliance

Managing febrile neutropenic patients

-Re-evaluate after 48-72 H of empiric tx -Modifications may be needed, esp in prolonged neutropenia -Pathogen directed tx -Median time to defervescence: 5-7d

Pathogen-directed tx for MRSA

Vanc

Pathogen-directed tx for VRE

Daptomycin or linezolid

Pathogen-directed tx for ESBL

Carbapenem

Pathogen-directed tx for KPC

Meropenem/vaborbactam Imipenem/cilastatin/relebactam Ceftazidime/avibactam

Pathogen-directed tx for NDM/IMP/VIM

Cefiderocol

Oral antimicrobial regimens for low-risk pts with febrile neutropenia

Ciprofloxacin + amox/clav Levofloxacin Ciprofloxacin + clindamycin

When to add antifungal tx in febrile neutropenia

-Pts with persistent fever/develop new fever with undocumented infection after 4-7 days of broad-spectrum antibiotics *<50% of positive fungal blood cultures (difficult to identify)

Tx options for antifungal tx

1. Amphotericin B deoxycholate or liposomal amphotericin B 2. Azoles (fluconazole, voriconazole, posaconazole, isavuconazole) 3. Echinocandins (micafungin, caspofungin, anidulafungin)

Tx duration of antifungal agents in febrile neutropenia

Continue tx for 2 weeks in absence of s/sx of invasive fungal infections -Often continued for duration of neutropenia

When to initiate antiviral tx

Vesicular/ulcerative skin or mucosal lesions (evaluate for HSV/ZVZ) Presumed/confirmed viral infection (initiate antivirals to aid in healing lesions and preventing dissemination)

Antiviral tx options for HSV/VZV

Acyclovir Valacyclovir

Antiviral tx options for CMV

Ganciclovir Valganciclovir

Most common catheter-related bloodstream infections

S. aureus S. epidermidis

Indications for catheter removal in febrile neutropenia ("pulling the line")

-Subcutaneous tunnel infection -Failure to clear blood cultures after 72H of appropriate antimicrobial tx -Persistent fever -Septic emboli -Pathogens (usually from biofilm formation)

Common pathogens in febrile neutropenia catheter-related blood stream infection requiring catheter removal

-Fungi -Mycobacteria -P. aeruginosa -Bacillus spp -C. jeikeium

Management of febrile neutropenia 1. MOST IMPORTANT determinant in pt outcomes is __________. 2. Which patients are recommended to use CSF?

1. Resolution of neutropenia 2. CSF (filgrastim & sargramostim) --> recommended in pts with ANC<500, uncontrolled primary disease, PNA, IFI, hypotension, sepsis, multiorgan dysfunction **Patients with prolonged neutropenia and documented infection who are NOT responding to antimicrobial tx may benefit

Most important thing to remember about resolution of neutropenia

Meds only do so much -- it must be the patient's body to fully eradicate the infection

Which patients get prophylaxis for febrile neutropenia?

-Moderate and high risk pts with expected ANC < 100 for > 7d -Heme malignancies (AML, MM, lymphoma, CLL) -Allogenic & autologous HSCT -Graft vs host disease with high dose steroids -Use of alemtuzumab

What med is used as prophylaxis for febrile neutropenia

FQ (ciprofloxacin or levofloxacin)

What should be done if there is a breakthrough infection with FQ prophylaxis?

Do NOT use FQ in empiric tx regimen

Antifungal prophylaxis -Used for pts with ____ & ____ -Tx options include _______ IF AML, MDS, GVHD on high dose steroids: ____ & ____

-Allogenic HSCT; intensive induction for acute leukemia -Azoles (DOC) -Echinocandins (if can't use azoles) IF AML, MDS, GVHD on high dose steroids: posaconazole or isavuconazole

Antiviral prophylaxis -HSV seropositive pts undergoing allogenic HSCT or leukemia induction tx: _______ -Annual _____ influenza vaccine recommended for ____ patients -Varicella vaccine

Acyclovir INACTIVATED; ALL

What med is given to pts getting allogenic HSCT and GVHD on high dose steroids? Why?

TMP-SMX Substantially reduces the risk of PJP