Infections in Immunocompromised Patients Flashcards
What is an immunocompromised host?
patient with intrinsic or acquired defects in host immune defenses that predispose to development of infectious complications
What are the risk factors for infection?
neutropenia, immune system defects, destruction of protective barriers, environmental contamination/alteration of microbial flora
What is neutropenia?
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
What are immune system defects?
defects in cell-mediated immunity
defects in humoral immunity
What are destructions to protective barriers?
skin, mucous membranes, surgery
What are environmental contaminations/alterations of microbial flora?
transfer of organisms from patient to patient via health-care workers
contaminated equipment, water, and/or food
alteration of normal flora in hospital setting
What are risk factors for neutropenia?
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
What are common pathogens associated with infections - bacteria?
s. aureus, s. epidermidis, streptococci, enterococcus spp., enterobacterales, P. aeruginosa
What are common pathogens associated with infections - fungi?
candida spp., aspergillus, zygomycetes (mucor, rhizopus)
What are common pathogens associated with infections - viruses?
herpes simplex virus
varicella zoster virus
cytomegalovirus
What is cell mediated immunity?
T-lymphocytes (cytotoxic, helper, memory cytotoxic T cells)
primary defense against INTRACELLULAR pathogens
What is humoral immunity?
B-lymphocytes (plasma cells, memory B cells)
primary defense against EXTRACELLULAR pathogens
What causes defects in T-lymphocytes and macrophage function?
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
What causes defects in B-lymphocyte function?
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
What causes destruction of the skin’s protective barrier?
venipuncture, lines/ports
common pathogens: bacteria - S. aureus, S. epidermidis, candida spp.
What causes destruction of mucous membranes protective barrier?
chemo, radiation
common pathogens: bacteria - S. aureus, S. epidermidis, streptococci, enterobacterales, P. aeruginosa, bacteroides spp; fungi - candida spp.; viruses - HSV
How does surgery cause destruction of protective barriers?
solid organ transplant patients
common pathogens: bacteria - S. aureus, S. epidermidis, enterobacterales, P. aeruginosa, bacteroides spp; fungi - candida spp.; viruses - HSV
What is environmental contamination?
gram negative bacteria and fungi from fruits/veggies
legionella from water contamination
contaminated medical equipment
colonize skin, oropharynx, GI tract
What is alteration of microbial flora?
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
What is the epidemiology of infections in neutropenic cancer patients?
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
What is the etiology of bacterial infections?
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
What is the etiology of invasive fungal infections?
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
What is the etiology of viruses?
HSV most common; reactivation –> typically manifests as oral or genital infection
What is the etiology of protozoa?
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
What is the clinical presentation and diagnosis?
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
What is the criteria for low risk febrile neutropenia?
neutropenia </= 7 days
clinically stable
no medical comorbidities
inpatient or outpatient, IV and/or PO
What is the criteria for high risk febrile neutropenia?
ANC </=100 cells/mm^3 AND neutropenia >7 days
clinically unstable
medical comorbidities
HSCT
inpatient, IV therapy
What is the empiric antimicrobial treatment regimen for low risk febrile neutropenia?
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
What is the empiric antimicrobial treatment regimen for high risk febrile neutropenia?
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
What is the empiric antimicrobial regimen - beta-lactam monotherapy?
cefepime 2gm q8h
piperacillin/tazobactam 4.5gm q6h
ceftazidime 2gm q8h
imipenem 500mg q6h
meropenem 1gm q8h
When do we start vancomycin for the management of febrile neutropenia?
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
What to do if patient has penicillin allergy?
avoid beta-lactams, including carbapenems, if h/o immediate type I hypersensitivity rxn (hives, anaphylaxis)
instead use: ciprofloxacin + aztreonam + vancomycin
When would you initiate an oral antimicrobial regimen?
in low risk pts
options: ciprofloxacin + amoxicillin/clavulante; levofloxacin; ciprofloxacin + clindamycin
don’t use in pts already on FQ prophylaxis
What is the targeted therapy for management of febrile neutropenia?
pathogen-directed therapy:
MRSA –> vancomycin
VRE –> daptomycin or linezolid
ESBL –> carbapenem
KPC –> meropenem/vaborbactam, imipenem/cilastatin/relebactam, ceftazidime/avibactam
NDM/IMP/VIM –> cefiderocol
When to initiate antifungal therapy?
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
What are the treatment options for antifungal therapy?
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
When to initiate antiviral therapy?
vesicular/ulcerative skin or mucosal lesions (evaluate for HSV/VZV)
presumed or confirmed viral infection: initiate antivirals –> aid in healing lesions and preventing dissemination
What are the treatment options for antiviral therapy?
HSV/ZVZ: acyclovir, valacyclovir
CMV: ganciclovir, valganciclovir
What are the indications for catheter removal?
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
What is the most important determinant in patient outcomes?
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
When to use prophylaxis?
moderate-high risk patients with expected ANC </= 100cells/mm^3 for >7 days; heme malignancies (AML, MM, lymphoma, CLL); allogeneic and autologous HSCT; GVHD with high-dose steroids; use of alemtuzumab
Fluoroquinolone prophylaxis
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
What is antifungal prophylaxis?
when to use: allogeneic HSCT; intensive induction chemo for acute leukemia
azoles; echinocandins
AML, MDS, GVHD on high-dose steroids: posaconazole or isavuconazole
What is antiviral prophylaxis?
when to use: HSV seropositive pts undergoing allogeneic HSCT or leukemia induction therapy
use acyclovir
annual inactivated flu vaccine for all pts
varicella vaccine
When to use TMP/SMX prophylaxis?
allogeneic HSCT and GVHD on high-dose steroids
PJP pneumonia
