Term
| Fever in a Neutropenic pt |
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Definition
considered a medical emergency; a delay in therapy is associated with up to 70% mortality;
S/Sx of infection are either absent or muted in the absence of neutrophils, with this being the only reliable indicator;
Majority of incidences due to Gram-Pos organisms; |
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Term
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Definition
granulocytes, PMNs, segs;
All are phagocytic cells that destroy microorganisms;
Account of >95% of all granulocytes;
Most sensitive to myelosuppressive chemotherapy: short life span (9-10 days in bone marrow, live <1 day once released), rapid turnover; |
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Term
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Definition
Fever: single temp >=38.3 C (101 F);
Absolute Neutrophil Count (ANC) <500 or <1000 & a prediceted decline to <=500 over next 48 hrs; |
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Term
| Absolute Neutrophil Count (ANC) |
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Definition
| WBC x [(% Neutrophils + % Bands)/100] |
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Term
| Bone Marrow Suppression (Myelosuppression) |
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Definition
| most common dose-limiting toxicity of conventional chemotherapy |
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Term
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Definition
lowest concentration of WBCs in the peripheral blood following chemotherapy;
Occurs by 7-14 days after chemo, full recovery by 21-28 days |
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Term
| Chemotherapy is given on a q3-4 wk schedule |
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Definition
Most chemo is given on this schedule to allow ANC to recover;
Most chemotherapy for tx of solid tumors will be delayed until the ANC recovers; |
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Term
| Risk Factors for Infection |
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Definition
Threat of infection: ANC <1000;
Maximum risk: ANC <100;
Rapid fall in ANC;
Duration of neutropenia of >7 days;
Destruction of protective barriers: mucositis, invasive procedures;
Neoplastic obstruction;
Malnutrition; |
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Term
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Definition
| most important clinical finding |
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Term
| S/Sx of Infection may be ABSENT |
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Definition
| cough, sputum production, purulence, dysuria, frequency, urgency, dyspnea, erythema; |
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Term
| Lab Assessment for Neutropenic Fever |
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Definition
| CBC w/ differential, Chem-7, LFTs, vital signs, pulse oximetry |
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Term
| Diagnostic Tests for Neutropenic Fever |
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Definition
Blood cultures (peripheral & cather - obtain BEFORE antibiotic administration);
Culture of any clinically infected or suspicious sites;
Chest XRay;
Urinalysis, & Urine Culture |
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Term
| Goal of Initial Empiric Antibiotic Therapy |
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Definition
| Protect the neutropenic pt from early death because of undiagnosed infection |
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Term
| MASCC/IDSA Scoring Index for ID of Low-Risk Febrile Neutropenic Pts |
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Definition
Extent of Illness:
- No Symptoms (5 pts)
- Mild Symptoms (5 pts)
- Moderate Symptoms (3 pts);
NO HypOtension - systolic BP >=90 (5 pts);
NO COPD (4 pts);
Solid Tumor (4 pts);
NO Dehydration (3 pts);
Outpatient at onset of fever (3 pts);
Age <60 yrs (2 pts); |
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Term
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Definition
MASCC/IDSA Index: >=21 pts;
Pt has NO high risk factors, AND has most of these:
Outpt at time of fever onset;
No associated acute comorbidities;
Anticipated short duration of neutropenia (<7 days);
ECOG performance status of 0 to 1;
No hepatic or renal insufficiency;
Neutropenic fever can be treated as an outpatient;
Tx: oral antibiotics (ciprofloxacin + amoxicillin/clavulanic acid) as outpatient OR IV antibiotics as inpatient; |
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Term
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Definition
MASCC/IDSA Score: <21 OR have 1 of following risk factors on FIRST day of fever:
Inpatient at time of fever onset;
Clinically unstable or significant comorbidities;
Prolonged, severe neutropenia anticipated;
Abnormal renal or hepatic function;
Progressive or uncontrolled cancer;
Pneumonia or other complex infection;
Has received alemtuzumab;
Grade 3-4 mucositis;
Tx: MUST receive IV antibiotics as inpatient |
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Term
| Tx with Vancomycin in combination for High Risk Pts |
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Definition
Clinically obvious, serious catheter-related infections;
Intensive chemotherapy-produced mucosal damage;
Known colonization w/ pneumococci that are resistant to PCN & cephalosporins or MRSA;
Hypotension, cardiovascular impairment;
Prophylaxed w/ FQNs or TMP/SMX prior to developing fever;
Blood culture (+) for Gram-Pos bacteria before final ID & susceptibility testing;
D/C if drug is initiated and cultures remain negative after 24-48 hrs |
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Term
| Tx of Low Risk Pts w/ Neutropenic Fever |
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Definition
Oral: ciprofloxacin + amoxicillin-clavulanate;
IV Monotherapy:
- cefepime
- ceftazidime
OR
- carbapenem;
IV Dual Therapy:
- Aminoglycoside
PLUS
- antipseudomonal PCN, cefepime, ceftazidime, OR carbapenem
**Reasses after 3-5 days** |
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Term
| Tx of High Risk Pts with Neutropenic Fever |
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Definition
Vanco NOT Needed:
IV Monotherapy:
- cefepime, ceftazidime, OR carbapenem;
IV Dual Therapy:
- Aminoglycoside
PLUS
- antipseudomonal PCN, cefepime, ceftazidime, OR carbapenem;
VANCO NEEDED:
IV: Vancomycin
PLUS
Cefepime, ceftazidime, OR carbapenem
+/-
aminoglycoside;
**Reassess after 3-5 days** |
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Term
| Afebrile within 3 days of Treatment |
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Definition
If pathogen is identified, tailor Abx therapy to that pathogen;
Continue Abx until:
- cultures are NEGATIVE;
- sites of infection have resolved;
AND
- pt is free of S/Sx for >=7 days;
Desired ANC >500 prior to D/C of Abx;
If no pathogen is ID'd, continue for at least 7 days; |
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Term
| Persistent Fever Throughout 1st 3 days of ABX Tx |
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Definition
1) Reassess pt: culture results, drug levels, PhEX, CXR & Sinus XR, reculture, diagnostic imaging;
2) If no cause of infection ID'd, consider:
- nonbacterial infection, resistant bacterial infection, emergence of 2ndary infection, inadequate serum/tissue conc. of ABX, drug fever, infections at an avascular site;
Therapeutic Options:
- Continue inibital ABX;
- Change ABX (i.e. add vanco, change from ceph to carbapenem, D/C vanco);
- Add antifungal therapy +/- ABX therapy |
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Term
| Candida & Aspergillus spp. |
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Definition
| most common causative species of fungal infections in neutropenic pts |
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Term
| Candidates for Empiric Antifungal Therapy |
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Definition
| Neutropenic pts who remain febrile >=5 days of broad-spectrum ABX therapy |
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Term
| amphotericin B (Abelcet, Ambisome, Amphotec) |
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Definition
historically drug of choice for empiric antifungal tx in neutropenic pts;
MoA: binds to ergosterol on fungal cell membrane, altering permeability --> cell death;
WATCH DOSING: nephrotoxic;
ADRs:
- infusion-related rxns (fever, rigors, hypotension, N/V) --> premedicate w/ APAP, diphenhydramine;
- NEPHROTOXICITY;
- hypOkalemia, hypOmagnesemia; |
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Term
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Definition
azole antifungal NOT generally considered for neutropenic fever;
Indication: use in institutions at which mold infections & drug-resistant Candida species are uncommon;
PO/IV;
DO NOT use as tx in pts who received prophylactic doses; |
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Term
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Definition
Azole antifungal;
For invasive aspergillosis & other serious fungal infections;
Available PO & IV;
Dose: 6 mg/kg q12 hr x 2 doses, then 4 mg/kg q12 hr |
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Term
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Definition
azole antifungal;
Uses: tx of several invasive fungal diseases, activity against zygomycinetes (Mucor);
Only available PO, absorption highly dependent on coadministration with food; |
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Term
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Definition
echinocandin;
MoA: inhibits beta-glucan synthesis;
Uses: for invasive aspergillosis & candidemia;
**Lacks drug interactions with TACROLIMUS & CYCLOSPORINE that caspofungin has** |
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Term
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Definition
azole antifungal;
Uses: invasive aspergillosis & candidemia;
**NO HEPATIC Metabolism**
**NO Drug interactions**
Solubilized with EtOH - Flushing-type reaction when infused;
Loading dose required; |
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Term
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Definition
| most important determinant of duration of antibiotic therapy; |
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Term
| Continue Antimicrobial Therapy if... |
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Definition
| pt still has profound neutropenia (ANC <100), mucous membrane lesions in mouth/GI tract, and if vital signs are unstable |
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Term
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Definition
| pt appears clinically well with no evidence of infection & has been afebrile for 5-7 days |
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Term
| Antifungal therapy can be D/C'd when... |
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Definition
| neutropenia is resolved, pt is clinically well, & CT is negative |
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Term
| Herpes Simplex Virus/Varicella Zoster Infections |
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Definition
use antivirals only in neutropenic pts if skin or mucous membrane lesions are present;
TX: acyclovir, famcyclovir, or foscarnet |
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Term
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Definition
viral infection that may occur in BMT or HSCT recipients;
Must be isolateed from blood or bronchoalveolar disease;
Tx: valgancyclovir, gancyclovir, or foscarnet |
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Term
| Prevention of Neutropenia |
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Definition
Reverse isolation (pt must be masked & gowned when meeting with outside people);
Hand washing;
Exclude fresh fruits & veggies in diet;
Laminar airflow rooms - directs air away from pt; |
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Term
| G-CSF - granulocyte colony stimulating factor (filgrastim [Neupogen]) |
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Definition
stimulates production of NEUTROPHILS;
Dose: 5 mcg/kg SQ daily;
SEs: BONE PAIN, HTN, swelling, redness, hypersensitivity rxns, rare splenic rupture;
T1/2: 4 hrs;
Requires daily administration |
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Term
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Definition
pegylated form of G-CSF;
MoA: stimulates production of neutrophils;
Dose: 6 mg SQ with each chemo cycle;
- must be given w/in 48-72 hrs of end of each chemo cycle;
- can be given once q14 days
**Longer duration of action (T1/2: 80 hrs)** |
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Term
| GM-CSF - granulocyte-macrophage colony stimulating factor (sargramostim [Leukine]) |
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Definition
promotes proliferation of GRANULOCYTES (neutrophils & eosinophils) as well as MONOCYTES/MACROPHAGES;
Dose: 250 mcg/m^2/day SQ daily;
SEs: fever, chills, asthenia, BONE PAIN, HA, myalgia |
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Term
| Indications for use of CSFs |
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Definition
| prevention of neutropenic fever (NF) |
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Term
| Primary Prophylaxis with WBC CSFs |
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Definition
Recommended use in:
- chemo regimens expected to cause >20% incidence of febrile neutropenia;
- High Risk Pts including: age >65 yrs, poor performance status, previous episodes of febrile neutropenia, extensive prior treatment; |
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Term
| Secondary Prophylaxis with WBC CSFs |
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Definition
| use in pts who have experienced a neutropenic complication on a previous cycle of chemo WITHOUT CSF administration |
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Term
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Definition
| avoid the concomittant use of these in pts receiving chemotherapy AND radiation therapy --> potential for worsening myelosuppression; |
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