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57 Cards in this Set
- Front
- Back
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What is an immunocompromised host?
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Impaired immune defense (intrinsic or acquired)
Prolonged immunosuppression due to medicine --> opportunistic infections = morbidity and mortality |
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Risk factors for NF (general)
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Neutropenia
Immune system defects Destruction of protective barriers Environmental contamination and alteration of microbial flora |
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Neutropenia and ANC definition
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Abnormally low number of neutrophils <500 (critical point) but definitions vary
ANC = (WBC x 1000) x (PMN + bands (recorded in %)) |
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Risks of neutropenia
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- Degree and duration of neutropenia (<100 = profound, >7-10 days = greater risk)
- Rate of neutrophil decline after chemotherapy (faster = worse) - Normal number but abnormal function (leukemia, steroids, chemo, radiation) |
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What does duration of neutropenia depend on?
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-Chemotherapy type, treatment intensity
- HSCT have 0 neutrophils for 3-4 weeks |
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When is risk of death and infection greatest?
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ANC < 100 cells/mm3
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Neutropenia ranges and nadir
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Normal >1500, Neutropenia < 500, Profound < 100
Nadir: lowest measurement of cell line prior to recovery (7-10 days for WBC) *Oncologists determine level they are comfortable for treating* |
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Types of immune system defects leading to NF
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- Impaired immunity and ability to fight pathogens
- Poor T-lymphocytes, macrophages (cell-mediated) - B-cells (humoral) - Result of underlying disease or therapy (lymphoma, transplant, CLL, myeloma, splenectomy) |
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What causes hypogammaglobulinemia and what is it?
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Multiple myeloma, splenectomy, CLL = decreased humoral
Increased risk for encapsulated pathogens (S. pneuma, H. influ, N. meningitidis) |
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How are protective barriers (skin, mucous membranes) destroyed?
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- Surgery, venipuncture, IV and urinary catheters, radiation/chemo all disrupt barrier = more infection
- Skin disruption --> Staph and strep (skin flora) - Mucositis of GIT and oropharynx = port of entry bacteria, HSV and candida |
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What organisms in normal flora and environment can cause infection in immunocompromised?
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Contaminated equipment: pseudomonas, legionella
Contaminated food: G- bacteria, fungi Colonizing bacteria from GI translocation Frequent hospitalization: G- bacteria |
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How does alteration of normal flora cause infection? When does infections in hospitalized cancer patients occur from colonizing organisms?
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Colonizing bacteria (gut) via translocation cause 80% infections in cancer patients
Cancer colonization = G- bacilli (multiple hospital visits and on broad spectrum ABX often), 50% of hospitalized cancer infections occur AFTER admission |
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What is the etiology of infection in neutropenic cancer patients?
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- Occult infection in 50% FEBRILE neutropenic
- Microbiologically documented infection in 30-40% FEBRILE neutropenic (50% bacteremia) - Clinical documentation of s/s infection in 30-40% - ONLY fever s/s = 20-40% (hardest to treat) |
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Causative organisms of NF (general) Bacterial
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- G+ cocci (aureus, epidermis, strep, enter)
- G- bacilli (E. coli, klebsiella, pseudomonas) = used to be most common, less so now but on rise due to ABX resistance --> HIGH morbidity and mortality |
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Causative organisms of NF (general) Non-bacterial
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- Fungal (candida and aspergillus) due to extended therapy broad spectrum ABX (no normal flora to suppress fungus)
- Viral (CMV if transplant, HSV transplant or profound) - Parasitic (Pneumocystis, Toxoplasma) but less with Bactrim prophylaxis |
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What is the most common cause of acute bacterial infections in neutropenic infections?
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Gram + Cocci
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What is the KEY to successful treatment?
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Depends on neutrophil recover and resolution of neutropenia
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Gram + Pathogens in NF
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Majority of NF, S. epidermidis, Bacillus, Corynebacterium, Viridans strep, MRSA (if transplant or in/out hospital) and VRE (if transplant or in/out hospital)
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Gram - Pathogens in NF
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Important pathogens since high morbidity and mortality
E.Coli, klebsiella (ESBL Kleb is increasing) Increase in Enterobacter, Serrate, Citrobacter (hard to treat due to resistance) Pseudomonas (LESS in solid tumor, MORE in hematologic with high mortality), Stenotrophomonas and Burkholderia due to broad ABX Anaerobes (LESS likely unless MIXED infection) = Perirectal (colorectal cancer) cellulitis and oropharyngeal (head/neck cancer) infections |
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Fungi in NF
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- Candida (MOST common if albicans but other species rising with resistance)
- Aspergillus (80% mortality in HSCT) - Less so: Trichosporon, Fusarium, Curvularia, Think fungal if no response within 7 days of broad spectrum ABX |
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What are risks for fungal caused NF?
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Extended period of profound neutropenia, broad ABX use, steroid use
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Viral and Parasitic causes of NF
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- HSV (reactivation with mouth/genital lesions from mucosal damage of chemo or HSCT with antibodies)
-Pneumocystis jiroveci and Toxoplasma gondii (MOST common parasites but Bactrim prophylaxis helps) |
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Risks of parasitic NF and prophylactic drugs?
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Risk: hematologic malignancies and use of steroids
Prophylaxis: Bactrim, dapsone, pentamidine, atovquone |
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Clinical Presentation of NF fever
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Single oral temp of >/= 38.3 C (101 F) in absence of other causes (blood product or chemo reaction, cell lysis, underlying malignancy)
OR >/= 38 C (100.4 F) for 1 hour or more, FEVER can be ONLY s/s of infection |
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Clinical workup of NF patient
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- Physical exam (oropharynx/nose/sinus/GIT, lungs, urinary tract, skin, soft tissue, CNS, perineum, IV sites)
- Labs (ANC, CBC w/ diff, CMP) - Blood (2+ sets of 1 aerobic and 1 aerobic) includes vascular access devices for bacteria/fungal - Urine Cx - Imaging (CT, CXR, aspiration, biopsy), Viral dx - oropharyngeal lesions - Diarrhea - C.diff and stool cultures |
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What guideline do we follow for NF?
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There are multiple guidelines we follow (IDSA, ASCO, NCCN, ESMO) but many aspects remain unclear in treatment
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What are the goals of therapy?
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- Prevent early death from undo infection
- Prevent breakthrough infections (all types) - Treat established infections - Avoid unnecessary ABX to avoid resistance - Reduce morbidity and allow for antineoplastic therapy to continue - Minimize toxicity, cost, ADR while increasing QoL |
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Low risk on MASCC score
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>/= 21 points (lower death and serous complications): neutropeniais ≤ 7 days, clinically stable, few co-morbidities, no signs/sx ofinfection other than fever
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High risk on MASCC score
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< 21 points (high death and complication): Neutropenia > 7 days, Profound neutropenia, Clinically unstable, Multiple comorbidities, Focal infection, High risk tumor
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MASCC Risk Index Score
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- Burden of febrile neutropenia (illness)
0 pt: severe or moribund 3 pt: moderate s/s 5 pt: no s/s - No hypotension (> 90) = 5 pt - No COPD = 4 pt - Solid tumor or hematologic malignancy (no previous fungal infection) = 4 pt - No dehydration needing IV fluids = 3 pt - Outpatient = 3 pt - Age < 60 = 2 pt |
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Initial Risk Assessment per NCCN = low
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MASCC >/= 21, ECOG PS 0-1, no hepatic/renal issues, short duration (< 7 days), no acute comorbidities, outpatient with fever
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Initial Risk Assessment per NCCN = high
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MASCC < 2, inpatient with fever, clinically unstable or significant comorbidities, prolonged neutropenia 5X ULN ALT/AST, CrCl < 30, uncontrolled progressive cancer, pneumonia or other complex infection, Alemtuzumab, Mucositis grade 3-4
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What is general empiric therapy for NF
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Target: Pseudomonas, G- bacilli, staph since high morbidity/mortality,
Mono therapy of Anti-pseudo BL -Cephalo: cepepime or ceftazidime (avoid) -Carbapenem: imipenem/cilastin, meropenem, doripenem (can use but no data) -PCN: pip/tazo Dual: anti-pseudo BL + AG or anti-pseudo FQ, Mono or Dual + Vanco |
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Treatment FlowChart for NF for low risk
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Low Risk + good outpatient f/u + oral OK --> Cipro + Amox/Clav (observe after first dose 4-24 hours, if stable can discharge to outpatient care if f/u in place)
Low Risk + poor outpatient f/u OR oral not OK --> IV monotherapy (Pip/tazo, carbapenem, Cefepime, Ceftazidime) = consider step-down to PO when appropriate (afebrile, stable, no positive culture, functional GIT) and then observe like above |
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Treatment FlowChart for NF for high risk
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IV monotherapy (Pip/tazo, anti-pseudo carbapenem, cefepime, ceftazidime)
Add vanco if cellulitis, PNA, severe sepsis/shock, gram + in blood, suspected catheter infections, known MRSA colonization or resistant strep Add AG or anti-pseudo FQ if septic shock, gram - in blood or PNA If septic shock consider anti-fungal therapy |
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Treatment FlowChart for NF for follow-up for all levels
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Follow-up and reassess daily and adjust therapy based on clinical and microbiologic data
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What should drive monotherapy decisions? What drugs to avoid?
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Institutional susceptibility
No ertapenem or tigecycline since no pseudo coverage No ceftazidime since increase resistance in pseudomonas, serrate and enterobacter (ESBL and type -1 beta lactamases) and low G+ activity |
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Why us AG in dual therapy?
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Despite lack of G+ coverage, provides synergistic effects and lower resistance BUT caution if patient already on nephrotoxic drugs (QD dosing may be safe but controversial)
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Why use quinolones for dual therapy?
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- Cipro (best option for pseudomonas) = NOT as monotherapy since poor gram + coverage, NO moxi (no pseudo) and NO cipro if on FQ prophylaxis
Levo/cipro NO anaerobe coverage, Levo is good atypical and better gram + May need to use in combo regimen for PCN allergic pt |
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When to add Vanco?
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NOT recommended unless:
- Catheter infection (port or PICC) - Blood Cx positive for G+ prior to ID and sensitivity - Known colonization of MRSa or PCN/ceph resistant pneumococci - Hypotension or septic shock D/C if no G+ infection found after 2-3 days Reserve quinupristin, linezolid, dapto, televancin, ceftaroline for MDROs |
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Therapy escalation for NF
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- Persistent fever + no changes (stable, neutropenic) = no typical adjustments in first 2-4 days unless deterioration (continue if neutropenia not expected to last 7+ days keep regimen)
- Persistent fever + deterioration = add vanco OR additional G- coverage (dual therapy) OR consider antifungals |
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When to use antifungals in NF
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- Persistent fever after 4-7 days of appropriate ABX and neutropenia expected to last 7+ days) = Amphotericin, Caspofungin, Voriconazole
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Do we use Fluconazole?
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NO! High resistant candida strains and no activity to aspergillum, If used prophylactically, then this should not be used in empiric therapy
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When to do antiviral therapy for NF?
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If vesicular lesions or ulcerative skin or mucosal lesions (think HSV ,VZV, CMV)
Acyclovir, famciclovir, valacyclovir = HSV, VZV, Ganciclovir, Valganciclovir (cidofovir, foscarnet) = CMV Oseltamivir, Zanamivir = Influenza A & B Others: IVIG, Ribavirin, entecavir, lamivudine, tenofovir |
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Therapy de-escalation
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After 2-4 days of empiric therapy; reassess, If afebrile within 2-4 days = continue till neutropenia resolved or switch to PO
If afebrile after 2-4 days + prolonged neutropenia = switch to FQ prophylaxis Documented infections treated based on duration of what is appropriate for site and duration of neutropenia |
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What is the optimal duration of therapy for NF?
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Controversial!
- D/c if ANC >/= 500 for 2+ days, afebrile and clinically state for 48+ hours, no documented infection or pathogen isolated Low risk patients: ANC < 500 but afebrile and stable with - culture = can d/c after 5-7 afebrile days Profound neutropenia, lesions, unstable vitals or other risks = continue till ANC > 500 and clinically stable Persistent neutropenia + febrile but stable and no infection = 2 weeks |
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Duration of therapy for documented infections
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- Uncomplicated bloodstream
G+ = 7-14 days G - = 10-14 days - S. aureus = at least 2 weeks (typical is 4 biofilm) after 1st negative cx (longer if endovascular involvement) - Yeast >/= 2 weeks after 1st - cx - Consider catheter removal for certain bugs - STI, sinusitis, bacterial PNA = 7-14 days - Catheter removal: septic phlebitis, tunnel infection, port pocket infection - Fungal (mold/yeast): candida (min 2 weeks after 1 - cx), aspergillum (min 12 weeks) - Viral (HSV/VZV 7-10 days, influenza 10 days) |
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High risk febrile neutropenia prophylaxis |
ANC </= 10 and for >/= 10 days Hematologic malignancy - Acute leukemia - Allogenic HSCT GVHD with HD steroids - Alemtuzumab FQ for duration of neutropenia, fungal + viral prophylaxis |
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Medium risk febrile neutropenia prophylaxis |
Moderate duration of neutropenia 7-10 days Autologous HSCT Multiple Myeloma Lymphoma CLL Purine analog therapy Consider FQ for neutropenia Fungal + Viral prophylaxis - consider |
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Low risk NF prophylaxis |
Short duration of neutropenia </= 7 days
Solid tumor treated with conventional therapy NO prophylaxis (fungal or antibacterial) - Viral if HSV episode in past |
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Best PO bacterial prophylaxis and is it recommended? |
NOT recommended unless: high risk, profound for > 7 days, HSCT patient NO Bactrim = no pseudo, oral fungal, myelosuppression FQ preferred Cipro = no G+ coverage Levo = better G+ = PREFERRED |
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GCSF use |
NOT used in uncomplicated fever and neutropenia If high risk patient: - Can use for primary/secondary prophylaxis - Therapeutic use in NF - Reduce duration of neutropenia in HSCT |
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Prophylactic use of GSFC |
For curative intent, survival and QoL: - High risk (neutropenia > 20%): USE - Medium risk (10-20%): consider based on risks - Low (<10%): NO |
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What do you evaluate after second cycle? |
If the patient developed NF - consider giving G-CSF if no prior G-CSF - If on G-CSF, do dose reduction or change therapy |
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How to use G-CSF during NF |
If on Filgrastim --> continue If received Pegfilgrastim --> nothing additional No G-CSF --> risk factors for infection --> give G-CSF (unless no risks; then NO) |
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Types of G-CSF |
Filgrastim (Neupogen) 5 mcg/kg SQ 24-72 post chemo till post nadir recovery: short acting Pegfilgrastim (Neulasta/Onpro) 6 mg SQ once 24 hr after chemo that lasts 14 days - MUST make sure pt has 14 days till next chemo to use Biosimilars: Granix and Zarxio |
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Toxicities of G-CSF |
Common: Bone pain Other: splenic rupture, pulmonary toxicity with bleomycin, MDS/AML, ARDS |
