Infections in Immunocompromised Flashcards
Risk Factors for Infection
Neutropenia
- ANC < ___ cells/mm3
Immune system defects
Destruction of protective barriers
Environmental contamination/alteration of microbial flora
1000
Neutropenia
ANC < ___ cells/mm3
- ANC = WBC x (%polys + %bands)
Risk factors for infection
- High risk: ANC < ___ cells/mm3
- Highest risk: ANC < ___ cells/mm3
- ↑ rapidity of decline = ↑ risk
- ↑ duration = ↑ risk
- Highest risk with severe
neutropenia > __ - __ days
- 1000
- 500
- 100
- 7-10
Immune System Defects
Cell-mediated Immunity
- ___ lymphocytes
- primary defense against ___ pathogens
Humoral Immunty
- __ lymphocytes
- primary defense against ___ pathogens
- T
- intracellular
- B
- extracellular
Immune System Defects
Cell mediated immunity:
- defects in ___ and ___ function
- underlying disease
- ___ drugs
Reduced ability of host to defend against ___ pathogens
- T-lymphocyte, macrophage
- immunosuppressive
- intracellular
Immune System Defects
Humoral Immunity
- Defects in ___ function
- underlying disease
- immunosuppresive drugs
- Reduced ability of host to defend against ___ pathogens
- B-lymphocyte
- extracellular
Destruction of Protective Barriers
Skin
- ___ , lines, ports
Mucous Membranes
- ___ , radiation
Surgery
- transplants
- venipuncture
- Chemotherapy
Alteration of Microbial Flora
- Oropharyngeal flora rapidly change to primarily Gram ___ ___ in hospitalized patients
- Broad spectrum therapy has the greatest impact on normal flora
- 50% of infections in hospitalized cancer patients due to organisms acquired after admission
- ## negative, bacilli
Infections in Neutropenic Cancer Patients
- leading cause of death
- Profound neutropenia (ANC < ___ cells/mm3) = greatest risk of infection
- Febrile episodes attributed to ___ ___ infection in only 30-40% of cases
- 45-75% of bacteremic episodes in cancer patients are due to Gram ___ ___
- 500
- microbiologically documented
- positive cocci
Infections in Neutropenic Cancer Patients
Prolonged neutropenia + ___ antibiotics and/or ___ = highest risk
Candida spp.
- Candida albicans most common
- Up to 60% of cancer patients develop thrush
- Disseminated infections: Damaged mucous membranes → colonized with Candida → enter bloodstream
- Isolated in blood < 25% of patients infected with Candida
Aspergillus spp.
- Heme and HSCT patients – ___ neutropenia
- Inhalation of airborne spores → lung colonization → invasion of lung parenchyma and pulmonary vessels → hemorrhage/pulmonary infarcts → mortality (35-80%)
- Sinusitis, disseminated disease
- broad-spectrum, steroids
- prolonged
Viruses
HSV
- Clinical disease in patients with serologic evidence of prior infection
- ___ → typically manifests as oral or genital infection
- Can disseminate in rare cases
- Reactivation
Protozoan
Pneumocystis jirovecii (PJP)
- Typically manifests as severe lung infection
Toxoplasma gondii
- Lung, brain, and eye disease
___ prophylaxis has drastically reduced the incidence of both these infections
Trimethoprim-sulfamethoxazole (TMP/SMX)
Clinical Presentation and Diagnostics
Presence of ___ - most important finding, may be only clinical finding
- Other signs/symptoms of infection usually absent due to ___
fever
neutropenia
Management of Febrile Neutropenia
Low Risk
- neutropenia ≤ __ days
- clinically stable
- inpatient or outpatient (IV and/or PO)
High risk
- ANC ≤ ___ cells/mm3 AND neutropenia > __ days
- Clinically unstable
- Inpatient, IV therapy
- 7
- 100, 7
Management of Febrile Neutropenia
Empiric antimicrobial treatment regimens
- shoud cover likely pathogens
- should include ___ coverage
- antipseudomonal
Management of Febrile Neutropenia
β-lactam monotherapy
- ___ 2gm q8h
- ___ 4.5gm q6h
- ___ 2gm q8h
- ___ 500mg q6h
- ___ 1gm q8h
Pros
- comparable efficacy to ___ regimens
- ↓ toxicities/cost
- easier administration
Cons
- no gram ___ activity eith ceftazidime
- selection of resistant organisms
- ↑ colonization and superinfection rates
- cefepime
- piperacillin/tazobactam
- ceftazidime
- imipenem
- meropenem
- combination
- positive
Management of Febrile Neutropenia
Addition of ___ NOT recommended as standard part of ___ emperic regimen per IDSA
Indications for addition of Gram-positive agent
▪ Hemodynamic instability/sepsis
▪ ___
▪ Blood cultures growing Gram-positive bacteria
▪ Line/port infection
▪ ___
▪ Severe ___
▪ Colonization with resistant Gram-positive bacteria
- Vancomycin, initial
- Pneumonia, SSTI, mucositis
Management of Febrile Neutropenia
Penicillin allergy
- Avoid β-lactams, including carbapenems, if history of immediate type I hypersensitivity reaction (hives, anaphylaxis)
- ___ + ___ + ___
Oral antimicrobial regimens (low risk pts)
- ciprofloxacin + ___
- levofloxacin
- ciprofloxacin + ___
Pros
- comparable efficacy to ___ regimen
- ↓ cost
- ↓ exposure to nosocomial pathogens
Cons
- less data
- requires patient compliance and 24 hr access to medical care if instability develops
- not to be used in patents already on ___ prophylaxis
- Ciprofloxacin + aztreonam + vancomycin
- amoxicillin/clavulanate
- clindamycin
- IV
- FQ
Management of Febrile Neutropenia
Targeted therapy
- re-evaluate after __ - __ hrs of empiric therapy
- Modifications may be needed, especially in prolonged neutropenia
- Pathogen-directed therapy
- Median time to defervescence __ - __
days
Pathogen-directed therapy
- MRSA → ___
- VRE → ___ or ___
- ESBL → ___
- KPC → ___ /vaboractam,
___ /cilastatin/relebactam,
___ /avibactam
- NDM/IMP/VIM → ___
- 48-72
- 5-7
- vancomycin
- daptomycin, linezolid
- carbapenem
- meropenem, imipenem, ceftazidime
- cefiderocol
Initiation of antifungal therapy
- Patients with persistent fever or develop new fever with undocumented infection after 4-7 days of ___ antibiotics
Treatment options
- ___ deoxycholate or liposomal amphotericin B
- ___ , voriconazole, posaconazole, isavuconazole
▪ Echinocandins: ___, caspofungin, anidulafungin
Continue therapy for __ weeks in absence of s/sx of IFI
- Often continued for duration of ___
- broad-spectrum
- Amphotericin B
- fluconazole
- Micafungin
- 2
- neutropenia
Antiviral therapy
Treatment options
HSV/VZV
- ___ , ___
CMV
- ___ , ___
- Acyclovir, valacyclovir
- Ganciclovir, valganciclovir
Catherter-realted bloodstream infections
___ and ___ most common
- S. aureus, S. epidermidis
T or F: Optimal duration is controversial
TRUE
Most important determinant in patient
outcomes – ___ of neutropenia
Colony-stimulating factors (CSFs)
- ___ (G-CSF) and sargramostim (GM-CSF)
May be useful in patients with ANC ≤ ___
cell/mm3, uncontrolled primary disease, PNA, IFI, hypotension, sepsis, multiorgan dysfunction
Patients with prolonged neutropenia and documented infection who are NOT responding to antimicrobial therapy may benefit from CSFs
Pros
- ↓ duration/severity of neutropenia
- ↓ duration of antimicrobial therapy
- ↓ hospitalizations
- ↓ hospital length of stay
Cons
- No benefit in overall mortality
- No benefit in infection-related mortality
- resolution
- Filgrastim
- 500
Prophylaxis
Fluoroquinolone prophylaxis
- ___ or ___
- ↓ incidence of ___ and documented Gram ___ infections
- May ↓ risk of death
- Ciprofloxacin poor activity against Gram-
___ organisms
Breakthrough infection on FQ prophylaxis
- Do NOT use FQ in empiric treatment
regimen
- cipro, levo
- fever, negative
- positive
