Infections in Immunocompromised Flashcards
Risk factors for infection
Neutropenia: reduction in the amount of circulating neutrophils, ANC < 1000 cells/mm^3, severity, rate of decline, and duration of neutropenia
Immune System Defects: defects in cell-mediated and humoral immunity
Destruction of Protective Barriers: skin, mucous membranes, surgery
Environmental contamination/alteration of microbial flora: transfer of organisms from patient to patient, contaminated equipment, water, food, alteration of normal flora in hospital setting
Neutropenia
ANC < 1000 cells/mm^3
ANC= WBC x (%polys + % bands)
High risk: ANC < 500 cells/mm3
Highest risk: ANC < 100 cells/mm3
increase rapidity of decline=increase risk
increase duration=increase risk
Highest risk with severe neutropenia > 7-10 days
Common bacteria pathogens
S. aureus
Enterobacterales
P. aeruginosa
S. epidermis
Strep
Enterococcus
Common fungi pathogens
Candida spp
Aspergillus
Zygomytes: mucor, rhizopus
Common virus pathogen
HSV
VZV
CMV
Skin
Venipuncture, lines/ports
Common pathogens: S. aureus, S. epidermis, Candida spp.
Mucous Membranes
Chemotherapy, radiation
Bacteria: S. aureus, Enterobacterales, P. aeruginosa , S. epidermis, Strep, Enterococcus
Fungi: Candida
Virus: HSV
Surgery
Solid organ transplant patients
Bacteria: S. aureus, Enterobacterales, P. aeruginosa , S. epidermis, Enterococcus
Fungi: Candida
Virus: HSV
Alteration of Microbial Flora
Oropharyngeal flora rapidly change to primarily gram-negative bacilli in hospitalized patients
50% of infections in hospitalized cancer patients due to organism acquired after admission
Broad spectrum therapy has greatest impact on normal flora
Pathogens: Enterobacterales, P. aeruginosa, S. aureus, Candida, Aspergillus
Infections in Neutropenic Cancer patients
Profound neutropenia (ANC < 500)= greatest risk of infection
Common sites of infection: lungs, skin, sinuses, oropharynx, GI tract
Febrile episodes attributed to microbiologically documented infection in only 30-40% of cases
45-75% if bacteremic episodes in cancer patients are due to gram + cocci
Invasive fungal infections
Prolonged neutropenia + broad spectrum antibiotics and/or steroids= highest risk
Candida albicans is most common: up to 60% of cancer patients develop thrush
Aspergillus spp.
- Heme and HSCT patients–>prolonged neutropenia
- Sinusitis, disseminated disease
Protozoan infections
PJP: severe lung infection
Toxoplasma gondii: lung, brain, and eye disease
Bactrim prophylaxis has drastically reduced the incidence of both these infections
Clinical Presentation
Presence of fever–>most important finding
- ≥ 38.3 C (≥ 101 F) or oral temperature ≥ 38 C (≥ 100.4 F) persisting for 1 hour or longer
Non-infectious causes: blood products, chemo, drug fever, underlying malignancy
Other signs/symptoms of infection usually absent due to neutropenia
Diagnostics
Blood cultures, CBC, BMP or CMP
Imaging, aspiration or biopsy
Infection risk assessment
Evaluation at time of fever dictates IV vs PO, inpatient vs outpatient, duration
Low risk: neutropenia < or equal to 7 days, clinically stable, inpatient or outpatient, IV and/or PO
High risk: ANC < 100 AND neutropenia > 7 days, clinically unstable, inpatient, IV
Low risk–> adequate outpatient infrastructure, candidate for oral regimen
Oral FQ + Augmentin
Observe after first doe for 4-24 hours, patient remains stable, tolerates antibiotics, follow-up plan in place, close proximity, discharge to outpatient care
Treat 7-14 days as indicated by type/site of infection and until ANC > 500 and rising
Low risk–> Inadequate outpatient infrastructure or not a candidate for oral regimen
IV monotherapy: Zosyn, carbapenem, cefepime, ceftazidime
Consider step-down to PO when afebrile < or equal to 72 hours of starting IV therapy, hemodynamic stability, absence of positive cultures, ability to take PO
Empiric Regimens
B-lactam monotherapy:
- Cefepime 2 g q8h
- Zosyn 4.5 g q6h
- Ceftazidime 2 g q8h
- Imipenem 500 mg q6h
- Meropenem 1 g q8h
Addition of Vancomycin
NOT recommended as standard part of initial empiric regimen
Indications for addition of vancomycin:
- Hemodynamic instability/sepsis
- Pneumonia
- Blood cultures growing gram (+) bacteria
- Line/port infection
- SSTI
- Severe mucositis
- Colonization with resistant gram (+) bacteria
Allergies and oral regimens
PCN Allergy:
- Avoid B-lactams, including carbapenems, if history of immediate type I hypersensitivity reaction (hives, anaphylaxis)
- Ciprofloxacin + aztreonam + vancomycin
Oral: Low risk patients
- Ciprofloxacin + augmentin
- Levofloxacin
- Ciprofloxacin + clindamycin
Pathogen-directed therapy
Evaluate 48-72 hours after empiric
MRSA: Vancomycin
VRE: Daptomycin or Linezolid
ESBL: Carbapenem
KPC: Meropenem/vaborbactam, imipenem/cilastatin/relebactam, ceftazidime/avibactam
NDM/IMP/VIM: cefiderocol
High risk
Inpatient IV antibiotics: Zosyn, carbapenem, cefepime, ceftazidime
Add IV vancomycin when indicated
For septic shock, gram (-) bacteremia or pneumonia: add aminoglycoside or FQ, consider anti-fungal therapy for septic shock
Treatment of Neutropenia
Colony-Stimulating Factors (CSF)
- ANC ≤ 500 cells/mm3, uncontrolled disease, PNA, IFI, hypotension, sepsis, multiorgan dysfunction
Antifungal treatment
Who?
- high incidence of fungal infection on autopsy
- persistent fever or new fever with undocumented infection after 4-7 days of broad-spectrum antibiotics
- < 50% positive blood culture in neutropenic patient with IFI
Amphotericin B or liposomal amphotericin B
Azoles
Echinocandins
Duration: 2 weeks
