Infections in Immunocompromised Patients

Question 1

What is an immunocompromised host?

Answer 1

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

Question 2

What are the risk factors for infection?

Answer 2

neutropenia, immune system defects, destruction of protective barriers, environmental contamination/alteration of microbial flora

Question 3

What is neutropenia?

Answer 3

reduction in # of circulating neutrophils
absolute neutrophil count (ANC) less then 1000 cells/mm^3
severity, rate of decline, and duration of neutropenia affect mortality

Question 4

What are immune system defects?

Answer 4

defects in cell-mediated immunity
defects in humoral immunity

Question 5

What are destructions to protective barriers?

Answer 5

skin, mucous membranes, surgery

Question 6

What are environmental contaminations/alterations of microbial flora?

Answer 6

transfer of organisms from patient to patient via health-care workers
contaminated equipment, water, and/or food
alteration of normal flora in hospital setting

Question 7

What are risk factors for neutropenia?

Answer 7

high risk: ANC < 500 cells/mm^3
highest risk: ANC < 100 cells/mm^3
increased rapidity of decline = increased risk
increased duration = increased risk
highest risk with severe neutropenia >7-10 days

Question 8

What are common pathogens associated with infections - bacteria?

Answer 8

s. aureus, s. epidermidis, streptococci, enterococcus spp., enterobacterales, P. aeruginosa

Question 9

What are common pathogens associated with infections - fungi?

Answer 9

candida spp., aspergillus, zygomycetes (mucor, rhizopus)

Question 10

What are common pathogens associated with infections - viruses?

Answer 10

herpes simplex virus
varicella zoster virus
cytomegalovirus

Question 11

What is cell mediated immunity?

Answer 11

T-lymphocytes (cytotoxic, helper, memory cytotoxic T cells)
primary defense against INTRACELLULAR pathogens

Question 12

What is humoral immunity?

Answer 12

B-lymphocytes (plasma cells, memory B cells)
primary defense against EXTRACELLULAR pathogens

Question 13

What causes defects in T-lymphocytes and macrophage function?

Answer 13

underlying disease (hodgkin’s lymphoma) and immunosuppressive drugs –> reduced ability of host to defend against intracellular pathogens
pathogens: listeria, nocardia, legionella, mycobacteria, CMV, VZV, HSV, PJP, C. neoformans, candida, histoplasma capsulatum

Question 14

What causes defects in B-lymphocyte function?

Answer 14

underlying disease (CLL, multiple myeloma, spleenectomy) and immunosuppressive drugs (steroids, chemo agents) –> reduced ability of host to defend against extracellular pathogens
pathogens: bacteria (encapsulated), S. pneumoniae, H. influenzae, N. meningitidis

Question 15

What causes destruction of the skin’s protective barrier?

Answer 15

venipuncture, lines/ports
common pathogens: bacteria - S. aureus, S. epidermidis, candida spp.

Question 16

What causes destruction of mucous membranes protective barrier?

Answer 16

chemo, radiation
common pathogens: bacteria - S. aureus, S. epidermidis, streptococci, enterobacterales, P. aeruginosa, bacteroides spp; fungi - candida spp.; viruses - HSV

Question 17

How does surgery cause destruction of protective barriers?

Answer 17

solid organ transplant patients
common pathogens: bacteria - S. aureus, S. epidermidis, enterobacterales, P. aeruginosa, bacteroides spp; fungi - candida spp.; viruses - HSV

Question 18

What is environmental contamination?

Answer 18

gram negative bacteria and fungi from fruits/veggies
legionella from water contamination
contaminated medical equipment
colonize skin, oropharynx, GI tract

Question 19

What is alteration of microbial flora?

Answer 19

oropharyngeal flora rapidly change to primarily gram-negative bacilli in hospitalized patients (within 1st 48 hours)
broad spectrum therapy has the greatest impact on normal flora
common pathogens: enterobacterales, P.aeruginosa, S. aureus, candida, aspergillus

Question 20

What is the epidemiology of infections in neutropenic cancer patients?

Answer 20

infection is leading cause of death in neutropenic cancer patients
profound neutropenia (ANC < 500 cells/mm^3) = greatest risk of infection
common site of infection: lungs, skin, sinus, oropharynx, GI tract
febrile episodes attributed to microbiologically documented infection in only 30-40% of cases
45-75% due to gram-positive cocci

Question 21

What is the etiology of bacterial infections?

Answer 21

staphylococci: MSSA, MRSA, CoNS
viridans streptococci: mucositis
enterobacterales: E. coli, klebsiella spp.
P. aeruginosa: high morbidity + mortality
other: enterococci spp., lactobacillus, stenotrophomonas maltophilia, burkholderia cepacia

Question 22

What is the etiology of invasive fungal infections?

Answer 22

prolonged neutropenia + broad-spectrum antibiotics and/or steroids = highest risk
candida albicans most common: disseminated infections - damaged mucous membranes –> colonized with candida –> enter bloodstream
aspergillus spp.: heme and HSCT patients - prolonged neutropenia; inhalation of airborne spores –> lung colonization –> invasion of lung parenchyma and pulmonary vessels –> hemorrhage/pulmonary infarcts –> mortality

Question 23

What is the etiology of viruses?

Answer 23

HSV most common; reactivation –> typically manifests as oral or genital infection

Question 24

What is the etiology of protozoa?

Answer 24

PJP - typically manifests as severe lung infection
toxoplasma gondii - lung, brain, and eye disease
trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis has reduced the incidence of these infections

Question 25

What is the clinical presentation and diagnosis of febrile neutropenia?

Answer 25

presence of fever is most important finding: single oral temp of >/=38.3 or oral temp >/= 38 persisting for 1 hour or longer labs: blood cultures, CBC with differential, BMP/CMP diagnostics: imaging, aspiration or biopsy

Question 26

What is the criteria for low risk febrile neutropenia?

Answer 26

neutropenia

Question 27

What is the criteria for high risk febrile neutropenia?

Answer 27

ANC 7 days clinically unstable medical comorbidities HSCT inpatient, IV therapy

Question 28

What is the empiric antimicrobial treatment regimen for low risk febrile neutropenia?

Answer 28

should include antipseudomonal coverage! adequate outpatient infrastructure, candidate for oral regimen: oral FQ + amoxicillin clavulanate inadequate outpatient infrastructure or not a candidate for oral regimen: inpatient IV antibiotics (monotherapy) - piperacillin/tazobactam, antipseudomonal carbapenam, cefepime, ceftazidime

Question 29

What is the empiric antimicrobial treatment regimen for high risk febrile neutropenia?

Answer 29

inpatient IV antibiotics (monotherapy) - piperacillin/tazobactam, antipseudomonal carbapenam, cefepime, ceftazidime ADD IV vancomycin for cellulitis, pneumonia, severe sepsis or shock, gram-positive bacteremia, suspected IV catheter infection, known colonization with MRSA, or resistant streptococci for septic shock, gram-negative bacteremia or pneumonia: ADD aminoglycoside or antipsuedomonal FQ

Question 30

What is the empiric antimicrobial regimen - beta-lactam monotherapy?

Answer 30

cefepime 2gm q8h piperacillin/tazobactam 4.5gm q6h ceftazidime 2gm q8h imipenem 500mg q6h meropenem 1gm q8h

Question 31

When do we start vancomycin for the management of febrile neutropenia?

Answer 31

NOT recommended as standard part of initial empiric regimen indications for addition: hemodynamic instability/sepsis, pneumonia, blood culture growing gram-positive bacteria, line/port infection, SSTI, severe mucositis, colonization with resistant gram-positive bacteria

Question 32

What to do if patient has penicillin allergy?

Answer 32

avoid beta-lactams, including carbapenems, if h/o immediate type I hypersensitivity rxn (hives, anaphylaxis) instead use: ciprofloxacin + aztreonam + vancomycin

Question 33

When would you initiate an oral antimicrobial regimen?

Answer 33

in low risk pts options: ciprofloxacin + amoxicillin/clavulante; levofloxacin; ciprofloxacin + clindamycin don't use in pts already on FQ prophylaxis

Question 34

What is the targeted therapy for management of febrile neutropenia?

Answer 34

pathogen-directed therapy: MRSA --> vancomycin VRE --> daptomycin or linezolid ESBL --> carbapenem KPC --> meropenem/vaborbactam, imipenem/cilastatin/relebactam, ceftazidime/avibactam NDM/IMP/VIM --> cefiderocol

Question 35

When to initiate antifungal therapy?

Answer 35

if high incidence of fungal infection at autopsy or pt with persistent fever/develop new fever with undocumented infection after 4-7 days of broad-spectrum antibiotics

Question 36

What are the treatment options for antifungal therapy?

Answer 36

amphotericin B deoxycholate or liposomal amphotericin B azoles: fluconazole, voriconazole, posaconazole, isavuconazole echinocandins: micafungin, caspofungin, anidulafungin continue for 2 weeks in absence of s/sx of invasive fungal infection; often continued for duration of neutropenia

Question 37

When to initiate antiviral therapy?

Answer 37

vesicular/ulcerative skin or mucosal lesions (evaluate for HSV/VZV) presumed or confirmed viral infection: initiate antivirals --> aid in healing lesions and preventing dissemination

Question 38

What are the treatment options for antiviral therapy?

Answer 38

HSV/VZV: acyclovir, valacyclovir CMV: ganciclovir, valganciclovir

Question 39

What are the indications for catheter removal?

Answer 39

most commonly from S. aureus and S. epidermidis when to remove: subcutaneous tunnel infection, failure to clear blood cultures after 72hrs of antimicrobial therapy, persistent fever, septic emboli, pathogens present - fungi, mycobacteria, P. aeruginosa, bacillus spp, C. jeikeium

Question 40

What is the most important determinant in patient outcomes?

Answer 40

resolution of neutropenia patients with prolonged neutropenia and documented infection who are NOT responding to antimicrobial therapy may benefit from colony-stimulating factors: filgrastim and sargramostim no overall benefit in mortality, but decreases duration/severity of neutropnia and antimicrobial therapy

Question 41

When to use prophylaxis?

Answer 41

moderate-high risk patients with expected ANC 7 days; heme malignancies (AML, MM, lymphoma, CLL); allogeneic and autologous HSCT; GVHD with high-dose steroids; use of alemtuzumab

Question 42

Fluoroquinolone prophylaxis

Answer 42

ciprofloxacin or levofloxacin decreases incidence of fever and gram-negative infections; may decrease risk of death do NOT use FQ in empiric treatment regimen if on FQ prophylaxis

Question 43

What is antifungal prophylaxis?

Answer 43

when to use: allogeneic HSCT; intensive induction chemo for acute leukemia azoles; echinocandins AML, MDS, GVHD on high-dose steroids: posaconazole or isavuconazole

Question 44

What is antiviral prophylaxis?

Answer 44

when to use: HSV seropositive pts undergoing allogeneic HSCT or leukemia induction therapy use acyclovir annual inactivated flu vaccine for all pts varicella vaccine

Question 45

When to use TMP/SMX prophylaxis?

Answer 45

allogeneic HSCT and GVHD on high-dose steroids PJP pneumonia