infections in immunocompromised host a focus on febrile neutropenia
TRANSCRIPT
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Infections in Immunocompromised
HostA focus on Febrile Neutropenia
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Historical Background First description around 1900 Rare until development of chemotherapy In the 1960s: mainly in acute leukemia with profoundneutropenia G-ve sepsis most common with mortality = 90% Empirical therapy with synergistic combinations of antibioticsreduced mortality to + 10 % In the1980s: development of chemotherapy for solid tumorsleading to less severe and less protracted neutropenias For multiple reasons, replacement of G-ve infections by G+ve
→severity of infections decreases FN becomes a heterogeneous syndrome Risk-stratification models allow for identification of low risk
patients with additional treatment options Increase of fungal sepsis in specific groups of neutropenic patients
leads to widespread use of empirical antifungal agents
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Introduction Immunocompromised Host:
Patient with intrinsic or acquired defects in host
defenses
Increased risk of infection
Incidence is increasing – HIV/AIDS, organ transplant, and cancer pts
Infection remains the leading cause of autopsy-
determined death in neutropenic cancer patients
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Introduction Infectious complications are a major cause of
morbidity and mortality in cancer patients due
to advances in therapeutics of the malignancy.
Cytotoxic chemotherapeutic agents,
immunotherapy, and bone marrow transplant
almost invariably affect bone marrow function.
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Introduction The normal kinetics of blood cell turnover influence
the sequence and sensitivity of each of the formed
elements.
Polymorphonuclear leukocytes (PMNs; T1/2 = 6 to 8
h)
platelets (T1/2 = 5 to 7 days)
red blood cells (RBC; T1/2 ~ 120 days)
have most, less, and least susceptibility to usually
administered cytotoxic agents, respectively.
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The Causes and Consequences of Neutropenic Complications
Adapted from Lyman GH. Oncology. 2003:17(suppl):8-13.
Chemotherapy
Neutropenia
FEBRILE NEUTROPENIA
Complicated Infections
Prolonged Hospitalization
DEATH
Radiation Disease Process
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Introduction
Infections are the most common complication
of neutropenia
Febrile neutropenia is a MEDICAL
EMERGENCY!!!
Typically occurs 7-10d post chemo
Timely/Thorough assessment and antibiotics
are life saving
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Introduction
Risk of infection is proportional to severity
and duration of neutropenia
Recovery of ANC is the most important factor
determining the outcome of infectious
complications
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DefinitionsANC = (% segs or PMNS + % Bands) x WBC/100
• Neutropenia
– ANC <1000
– ANC <500 – what most treatment guidelines consider
critical
– ANC <100 – risk of infection and death is greatest
• Fever
– Single oral temp > 38.3° C (101° F)
– Temp > 38.0° for > 1 hour (100.4° F)
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NCCN Definitions of Neutropenia and Febrile Neutropenia
Neutropenia Fever
ANC <500/μLor
ANC <1000/μL and
a predicted decline to
≤500/μL
over the next 48 h
Oral temperature >38.3°C (single
reading) or
>38.0°C (>1 h)
fever + neutropenia = febrile neutropenia
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ANC example
Example 1
– WBC = 3.6
– 45% Segs
– 10% Bands
ANC = 55% (3600)/100
OR = 0.55 (3600)
= 1980
Example 2
– WBC 3.0
– 38% Neutrophils
ANC = 0.38 (3000)
= 1140
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Risk Factors for FN Patient-related
Age (>65 y) Female gender Poor performance status Poor nutritional status Decreased immune
function Conditions associated with
risk of serious infection Open wounds Active tissue infection
Comorbidities Chronic obstructive
pulmonary disease Cardiovascular disease Liver disease Kidney disease Diabetes mellitus Low baseline serum
hemoglobin level
NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.
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Risk Factors for FN Treatment-related
Type of chemotherapy (high-dose cyclophosphamides, anthracyclines)
History of severe neutropenia with similar chemotherapy
Preexisting neutropenia or lymphocytopenia
Extensive prior chemotherapy Concurrent or prior radiation
therapy to marrow-containing bone
Cancer-related Hematologic
malignancies Bone marrow
involvement with tumor Advanced or
uncontrolled cancer Elevated serum LDH
(lymphoma)
LDH = lactate dehydrogenase; RDI = relative dose-intensity.NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.
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Risk Factors for FN Altered skin defenses / foreign body
CVC Urinary / Foley catheter Radiation induced skin damage / cellulitis Surgery Mechanical ventilation Mucositis / Stomatitis
Colonization Recovery of an organism without clinical signs of infection Most infection are from bacteria that colonized the GIT,
URT, and Skin
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Incidence of Neutropenia and FN per Tumor Type and Regimen
Neutropenia RiskRegimen FN Other
Breast
Docetaxel, doxorubicin
33% Grade 3 or 4 neutropenia: 97%
Docetaxel, doxorubicin, cyclophosphamide
25% Grade 4 neutropenia: 88%
Doxorubicin, paclitaxel
32% Grade 4 neutropenia: 89%
Bladder
MVAC 26% Grade 3 or 4 leukopenia: 62%
Paclitaxel, carboplatin
21% Grade 3 or 4 neutropenia: 39%
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Neutropenia Risk
Regimen FN OtherSmall Cell Lung
Etoposide, cisplatin Fever: 18% Grade 3 or 4 neutropenia: 85%
Topotecan, paclitaxel 21% Grade 4 neutropenia: 96%
Non–Small Cell Lung
Carboplatin, paclitaxel 4% Grade 3 or 4 neutropenia: 63%
Cisplatin, paclitaxel 16% Grade 3 or 4 neutropenia: 75%
Colorectal
Irinotecan 14% Grade 3 or 4 neutropenia: 47%-48%
Non-Hodgkin’s Lymphoma
CHOP Hospitalization:
<age 65: 7.9%≥age 65: 13.8%5
Grade 3 or 4 leukopenia:34%-72%
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Other immune system defects
T-lymphocyte and macrophage function (cell-
mediated immunity) Transplant patients receiving immunosuppressive
drugs, HD, HIV
B-cell function (humoral immunity) Underlying disease such as multiple myeloma or
CLL
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Etiology of Infection
Primary site often includes alimentary tract and
where there has been damage to integument
– Site of infection can be documented in only 30% to
40% of febrile episodes Bacterial infections most common (fungal infections
increasing) Gram - replaced by Gram + organisms (often
methicillin resistant)
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Etiology of Infection
Check for other causes of feverReaction to blood products
chemotherapy
cell lyses and the underlying malignancy
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Etiology of Infection
Timeline helps narrow the differential
Early: Bacterial
Gram Positives (staph, strep …)
Gram Negatives (e.coli, klebsiella, Pseudomonas..)
Mixed in 25%
Infrequently anerobes
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Etiology of Infection
Late Candida
Aspergillosis
PCP (if on steroids)
Varied Viral
Herpes family( HSV, EBV, CMV,
RSV, Paraflu etc…
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Most Common Organisms Gram-Positive Cocci and Bacilli
Most likely if infected catheter
60-70% of documented infections, WHY? Staphylococcus species
Streptococcus species
Enterococcus faecalis / faecium
Corynebacterium species
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Most Common Organisms
Gram-negative Bacilli and CocciE. coli
Klebsiella sp.
Pseudomonas aeruginosa
Fungal infections: usually super infections Candida sp or other fungi can cause primary
infections
In BMT patients and prolonged N > 7 days
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Most Common Organisms
ViralMostly a reactivation of latent infections
Herpes Simplex, Varicella Zoster
CMV in Stem Cell Transplant
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Clinical Presentation Fever is the most important presenting symptom
in a neutropenic patient 60% of neutropenic patients who become febrile
have an established / occult infection 40% of patients based on a documented microbiological
origin
20% of patients based on clinical findings alone
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Clinical Presentation Many normal signs and symptoms of infection may
be absent, WHY? Inflammation may be minimal
⇓ or absent indurations, erythema, and postulation
normally seen in bacterial skin infections
Pneumonia without infiltrate, infiltrates may not develop
until ANC > 500
Meningitis without WBCs in CSF
UTI without pyuria
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Clinical Presentation
Most common sites of infection
lung→only fever and dry cough
Skin cellulitis → no pain, heat , erythema,
swelling
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Clinical Presentation Search should be undertaken for subtle signs and
symptoms PAIN at most commonly infected sites
Periodontium
Pharynx
Lower esophagus
Lung
Perineum
Skin
Bone marrow aspiration site
Catheter access sites
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Evaluation
Thorough Physical Exam
Cultures> 2 sets of blood cultures; 1 set from a central
venous access site and a peripheral vein
Any lesions suspected of being infected
Urine if any S&S of UTI, presence of catheter, or
abnormal U/A
Stool cultures if diarrhea present
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Evaluation
CXR if s/s of respiratory tract infection or if
outpatient therapy is planned
CBCWhat would you expect?
SrCr, BUN, and transaminases
Determine high and low risk patients (see
algorithm)
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Evaluation: Low/High risk neutropenia algorithm
Scores >= 21
considered low
risk
Other algorithms
available
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Factors that favor low risk ANC > 100
Duration of neutropenia < 7 days
Resolution of neutropenia expected in < 10 days
Normal CXR
No IV catheter site infection
Normal hepatic and renal function
No appearance of illness
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Treatment Algorithm
Outpatient Inpatient
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Treatment Empiric antibiotic therapy should be administered
promptly if afebrile, but signs and symptoms of infection present
If febrile with ANC< 500 or > 500 and predicted to < 500
Gm –ve infections have a 91% mortality in the 1st 24-48 hrs
Remove any sources of infection if possible
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Treatment
Initial antibioticsMust consider site of infection/ likely pathogen
Frequency of isolation
Antibiogram of hospital
Allergies
Concomitant treatments
Organ dysfunction
Must have bactericidal activity
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Treatment
Optimal antibacterial spectrumCover gm-ve bacilli : E.coli, K.pneumonia,
P.aeruginosa + staphylococci, streptococci
Optimal regimen remains controversial
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Proposed Classification/Management for FN Patients High Risk: Prolonged Neutropenia ( > 14 d),
Heme CA or allo BMT, substantial
comorbidity, unstable Admit, IV therapy (usually combination Rx) for duration of
neutropenia; Ampho B empiric Rx for continued fever
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Proposed Classification/Management for FN Patients
Moderate Risk: Neutropenia 7-14 d, auto BMT,
stable, minimal comorbidity Initial IV Rx (monotherapy OK), early discharge with po if
response; Ampho B for cont’d fever (especially if azole prophy)
Low Risk: < 7d neutropenia, solid tumor, stable Outpatient IV or po therapy; azole Rx ok for cont’d fever
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Candidates for Outpatient Therapy Appears stable
< 60 years
ANC > 100
No source identified
Responsive tumor
No comorbidity bleeding, BP, CA++, respiratory failure, altered MS
Suspected duration of neutropenia is not a determining
factor (can’t predict at time of febrile presentation)
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Oral antibiotics As initial therapy or as follow up therapy
Oral ciprofloxacin + amoxicillin-clavulanate
May use clindamycin in allergic patients
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Monotherapy
Monotherapy does not cover Coagulase-negative staphylococci
MRSA
Enterococcus (except imipenem covers faecalis)
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Monotherapy
Ceftazidime3rd generation cephalosporin/ antipseudomonal
covers only some gram + organisms
May improve staphylococcal cover with
vancomycin
Increasing resistance ( K.pneumonia produce β-
lactamases
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Monotherapy
Cefepime4th generation cephalosporin
FDA approved as monotherpay for FN
Low affinity for β-lactamases
more potent than Ceftazidime against gram +
organisms ( ↓ need for vancomycin)
Above advantage is lost when high rate of MRSA
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Monotherapy
CarbapenemsImipenem+ Cilastatin or meropenem
Broad spectrum against gm+ve and gm-ve +
anerobes
Evidence support efficacy
Higher incidence of N/V
More expensive
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Monotherapy- Summary Monotherapy is appropriate as initial empiric TX
No evidence to support superiority of one agent
Carbapenems are usually not used due to cost and
potential of resistance of Acinetobacter
Carbapenems reserved who failed initial empiric TX
or have Hx of infection with resistant organisms
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Monotherapy- Summary
Ineffective monotherapyMonobactams→lacks gm+ve activity
Fluoroquinolones →variable gm+ve activity, used
for prophylaxis
B-lactam/b-lactamase inhibitor combinations
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Two Drug Therapy
Advantages
Broad spectrum
activity
Potential synergy
Minimal emergence
of drug-resistant
strains
Disadvantages
Lack of G + activity
when AG + ceftaz is
used
Additive toxicities
when AGs are added
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Empiric Combinations
Anti-Pseudomonal PCN or 3rd G Cephalosporin +
aminoglycosideMost established combination
response rates all around 70%,
no advantage of one b-lactam over another
Disadvantage; nephrotoxicity, TDM
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Empiric Combinations
Double β-lactam; Anti-Pseudomonal PCN + 3rd G
Cephalosporin or Moxalactam Similar response rates
Limited experience
Poorer response in documented P. aeruginosa
less nephrotoxic, high cost
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Empiric Combinations
Ciprofloxacin + AG or B-lactamAssociated with ↑ gm +ve infections
Cipro activity against P. aeruginosa has ↓ (<70%)
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Empiric VancomycinRationale
Previous combinations lack activity against MRSA
Increasing gm+ve pathogens
Should be D/C after 3-5 days if G+ve infection not identified
Disadvantages
Excessive use → Vanco resistant organisms VRE/VRSA
↑ AG nephrotoxicity
Mortality from staphylococcal infections is < 4% in 1st 48 hrs →
can delay adding until pathogen is confirmed.
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Indications for Vancomycin Clinically suspected catheter/Skin related infection
Known colonization with resistant G+ve organism/MRSA
Positive blood culture for G+ve bacteria
Hypotension / CV impairment
Severe mucositis in hospitals with high MRSA (HD-Ara-C)
Quinolone prophylaxis
Severe Sepsis
In institution frequently isolating viridans streptococci
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Vancomycin Up Front? PRO
change in most common
isolates in F/N
? Less febrile days overall,
and perhaps less ampho B use
viridans streptococci may be
fatal; particular problem with
quinolone prophylaxis and
regimens that induce severe
mucositis
CON overall mortality from
documented gm(+)
bacteremia only 5%
vast majority of
patients with gm(+)
survive and respond to
addition of Vanco
VRE
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Alternatives to Vancomycin
LinezolidOxazolidione
IV or oral
Thrombocytopenia
Quinupristin-dalfopristinIV
High side effect profile
High potential for DI
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Drug Allergy
Need to assess type of allergy and determine
risk versus benefit
Know the organisms you need to cover
If unable to use β-lactam Vanc + Cipro
Vanc + Aztreonam
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Modifying Initial Empiric Regimen
Reassess after 3 days to determine efficacy of
regimenFever status
Clinical condition improved or deteriorated Changes made sooner if condition deteriorates
Etiologic pathogen identified
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Afebrile within 3-5 daysNo Etiology Identified
Continue empiric TX for 7 d
If ANC> 500 for 2 days→ may D/C Abs
D/C Abs after 14 days in prolonged neutropenia
without evidence of infection
ANC< 500 at 7 d with initial ANC< 100 or
mucositis or unstable → continue ABs
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Afebrile within 3-5 days
Etiology Identified
Additional antimicrobial or AB dosage adjustment
based on susceptibility tests and serum conc.
If persistently neutropenic→Maintain broad-
spectrum antibacterial coverage.
If neutropenia resolved →narrow therapy against
organism for appropriate duration
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Persistent Fever during 3-5 daysNo Etiology Identified Check for other causes of fever
Tumor lyses
Nonbacterial infection
Resistant bacterial infection
Inadequate serum and tissue levels of antibiotics
Slow response to therapy
Drug related fever
Emergence of a second infection/super infection
Infection at avascular site
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Persistent Fever during 3-5 daysNo Etiology Identified
RE-ASSESS patient! If re-assessment reveals
no new cause: 3 options
1) Continue current therapy
2) Change or add antibiotics
3) Add anti-fungal drug with or without
antibiotic change
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Persistent Fever during 3-5 daysNo Etiology Identified
1.Continue current therapy
Pt remains stable, not deteriorate
Neutropenia expected to resolve within 5 d
Continue Abs 4-5d after recovery of neutropenia
Continue Abs for 14 days with continued neutropenia
and reassess.
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Persistent Fever during 3-5 daysNo Etiology Identified
2.Modify initial Abs
If there is evidence of disease progressionCatheter site drainage, abdominal pain, pulm. Infilt
Add or change ABs
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Persistent Fever during 3-5 days
No Etiology Identified
3. Add antifungal
In pts with hematological CA, persistent fever,
neutropenia > 5d of Abs
Up to 1/3 of febrile neutropenic patients who
do not respond to a 1-week course of abx have
systemic fungal infections
Generally must cover Candida and Aspergillus
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Adding Amphotericin B Reliable activity against Candida and Aspergillus
addition of AmphoB appears to improve outcome
Considered DOC for empiric antifungal Tx
Continue until resolution of neutropenia
Persistent neutropenia→ 2 wk course
Documented infection → variable depending on
diagnosis
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Amphotericin B
0.7 mg/kg IV qd is the dose used in severe
infections
Rapid titration up to 0.7 mg/kg over 3 days is
used if infection is less severe
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Amphotericin B - Toxicities Infusion Related
F/C, N/V, HA, thrombophlebitis, myalgias and
arthralgias
Premeditation may reduce these symptoms
(Tylenol, Benadryl)
Meperidine can be given for rigors
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Amphotericin B - Toxicities
Nephrotoxicity80% of patients develop some type of impairment
Dose related
Potentiated by other nephrotoxins
Electrolyte Imbalances ⇓ K, Mg, Ca⇓ ⇓
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Lipid formulations of Ampho B
Similar efficacy
Decreased side effects (infusion related and
nephrotoxicity)
Consider in patients at risk for nephrotoxicity
or with underlying renal dysfunction.
Expensive
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Specific criteria for liposomal Ampho B Initial Creat > 2.0 and not on dialysis (long-term)
A doubling of serum creatinine and > 2.0 mg/dL
refractory disease after 10 days (or 500 mg) of
AmphoB
High risk patients (i.e. on CsA, tacrolimus, AG,
foscarnet, cis-platinum, ifosfamide;)
severe or persistent infusional AE to AmphoB
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Other Agents Fluconazole
May be used if mold infections (aspergillus sp)
and drug resistant candida sp are uncommon
Not for suspected aspergillus or who used FLZ
prophylaxis
ItraconazoleWhen FLZ is not indicated
Lower toxicity than AmphoB
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Other Agents Voriconazole
Increased activity against aspergillus and non-
albicans candida
Alternative to AmphoB
Less toxic, easier to administer
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Bottom Line, Empiric Therapy
IV lipo-amphotericin and itraconazole FDA approved,
Ampho-B is a standard of care and has most clinical
experience Caspofungin likely to be approved in near future
Data suggest adding ONLY after 96 hours of antibacterials
AND either persistent or recurrent fever at that time
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Bottom Line, Empiric Therapy Ampho B > Caspofungin > L-Ampho B > Itraconazole as
empiric Rx in patients previously receiving fluconazole
prophylaxis Voriconazole may have a role in high risk, long-term prophylaxis
(e.g. Allo BMT with GvHD), or as empiric therapy in high
aspergillus risk patient after initial blood Cxs (-), but not drug of
choice for empiric Rx of Fever/Neutropenia
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Antivirals Empiric use not indicated without evidence of
viral disease
Indicated if clinical or laboratory evidence of
viral disease Skin lesions due to herpes simplex or varicella-
zoster
Heal the lesions to decrease potential portals of
entry for bacteria and fungi
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Case 1
A 66-y.o. woman presents to her physician with fever, malaise, sore throat, and easy bruisability. She is diagnosed to have AML. Following induction chemotherapy, the patient becomes profoundly neutropenic (ANC≤ 100/mm3).
She is asymptomatic but develops a fever on the 3rd day of neutropenia. Her PE, which includes oral mucosa, indwelling vascular catheter site, heart, lungs, abdomen, and perianal region, is normal except for an oral temperature of 39°C. A CXR is normal, and blood cultures are obtained.
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Case 11. Which one of the following measures is
most appropriate?A) Obtain additional tests including sputum, throat,
and urine cultures; then initiate treatment with appropriate empiric antimicrobial therapy
B) Await results of blood cultures and initiate empiric antimicrobial therapy if clinical deterioration occurs
C) Initiate empiric therapy with imipenem and vancomycin
D) Initiate empiric therapy with cefepimeE) Initiate empiric therapy with ceftazidime and
tobramycin
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Case 12.Two sets of blood cultures grow gram-positive cocci
in clusters. The patient appears clinically stable except for continued fever. What is the most appropriate next step?
A) Await identification and antibiotic susceptibility of the organism before modifying antimicrobial therapy
B) Remove the indwelling intravascular catheter
C) Initiate therapy with vancomycin
D) Obtain additional blood cultures via catheter and peripheral vein
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Case 13.The gm-+ve cocci in the blood are identified
as MRSA. Despite appropriate management for the next 6 days, fever persists. Again, the patient appears stable with no other symptoms or signs of infection. Repeat blood cultures and CXR are negative. Which of the following is the best next step?
A) Change the patient’s antibacterial regimenB) Continue the same antimicrobial therapyC) Test for Clostridium difficile toxin in stool and
perform urinalysis and urine cultureD) Administer empiric antifungal therapy
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Duration of Therapy Neutrophil count is determinant of discontinuation
Afebrile by days 3 to 5 AND no infection identified ANC > 500 x 2 d, stop abx 48 h after afebrile AND ANC >
500
If ANC < 500 by day 7
If low risk and doing well, stop antibiotics when afebrile
x 5 to 7 days
If initially high risk, continue antibiotics
If an infection documented then titrate abx according
and continue a full course
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Duration of Therapy
Persistent Fever ANC > 500: Stop 4 to 5 days after ANC > 500
and reassess (if no infection ID’d)
ANC < 500: Continue for 2 weeks, reassess. If no
disease present and patient stable, discontinue
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Transfusion of granulocytes
has no role in the management of febrile neutropenia their exceedingly short half-life
mechanical fragility
clinical syndromes of pulmonary compromise with
leukostasis after their use.
Instead, colony stimulating factors (CSFs) are used to
augment bone marrow production of PMNs.
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Use of CSF Can significantly shorten the duration of neutropenia
Has not consistently reduced other measures of
febrile morbidity
Not routinely recommended
May be indicated when a worsening course is
predicted and there is an expected long delay in
recovery of marrow
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Mechanism Of Action
Granulocyte colony-stimulating factor (G-CSF), is
one of 5 "classic" hematopoietic growth factors that
are involved in the development and functional
activation of hematopoietic elements
These glycoproteins are produced naturally in
lymphocytes and monocytes, and have been
demonstrated to stimulate progenitor cells of different
hematopoietic cell lineages
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The 4 other classes of CSFs
granulocyte-macrophage colony-stimulating
factor (GM-CSF; sargramostim)
macrophage colony-stimulating factor (M-
CSF),
interleukin-3
erythropoietin
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Available Myeloid Growth Factors
Filgrastim
Recombinant methionyl
human G-CSF
175 amino acids
Half-life SC = 3.5 hours
Primarily renal clearance
Pegfilgrastim
Covalent conjugate
of recombinant methionyl
human G-CSF and
monomethoxypolyethylene
glycol
175 amino acids
Half-life SC = 15-80 hours
Limited renal clearance;
primarily neutrophil- mediated
clearance
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Available Myeloid Growth Factors
Sargramostim
Recombinant yeast-expressed human GM-CSF
127 amino acids
Half-life = 60 minutes
Indicated only for use following induction chemotherapy in
older adult patients with AML, for myeloid reconstitution
after BMT, and for mobilization of peripheral blood stem
cells for harvest
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Administration do not administer within 24 hrs of chemotherapy
G-CSF or GM-CSF is conventionally started 24 to 72
hrs after completion of chemotherapy and continued
until a PMN count of 1000 is achieved
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CSF Prophylaxis for First and All Subsequent Cycles: NCCN Guidelines
If the patient’s risk for FN* is:
If the patient is receiving:
Treatment with curative intent oradjuvant therapy
Treatment to prolong survival or improve QOL
Palliative therapy to manage symptoms or improve QOL
>20%(high)
Use CSF Use CSF Consider CSF (discuss high-risk chemotherapy with patient)
10%-20%(intermediate)
Consider CSF Consider CSF (discuss high-risk chemotherapy with patient)
Consider CSF (discuss high-risk chemotherapy with patient)
<10%(low)
CSF is not recommended for most patients†
CSF is not recommended
CSF is not recommended
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CSF Prophylaxis for FN Maintenance of Scheduled Dose Delivery Filgrastim
Daily dose of 5 µg/kg until post-nadir ANC recovery
to normal or near-normal levels Start 1-3 days after completion of chemotherapy and treat through
post-nadir recovery Pegfilgrastim
One dose of 6 mg per cycle of treatment Start 1-3 days after completion of chemotherapy There is evidence to support use for chemotherapy regimens given
every 3 weeks Phase 2 studies demonstrate efficacy in chemotherapy regimens given
every 2 weeksANC = absolute neutrophil count. NCCN. Myeloid Growth Factors in Cancer Treatment. V2.2005.
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Prophylaxis against Infection Non-Pharmacologic therapy
Reverse isolation
Infection control guidelines
Avoid fresh fruits and vegetables
Personal hygiene
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Prophylaxis against Infection
Antimicrobial ProphylaxisData supports efficacy of TMP-SMX, FQs,
fluconazole, and intraconazole to reduce # of
infectious episodes
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Prophylaxis against Infection Antimicrobial Prophylaxis
No absorbable antibacterial Theorized to reduce GI colonization
have not showmen consistent efficacy Lack of compliance
Induce resistance
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Prophylaxis against Infection Antimicrobial Prophylaxis
TMP-SMX showen consistent benefit in reducing bacterial infections
in FN patients
Effect on mortality less clear
Benefit must be weighed against risk of bone marrow
suppression, hypersensitivity, and emergence of resistance/
super infection
Should be strongly considered for patients at risk of PCP;
ALL receiving intensive chemo, AIDS, Allogenic BMT.
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Prophylaxis against Infection Antimicrobial Prophylaxis
FluoroquinolonesEqual or superior to TMP-SMX in preventing gm-
ve infections in FN
Disadvantages ↑ gm +ve in patients receiving prophylaxis
Emergences of resistant gm-ve bacilli
Does not reduce mortality
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Prophylaxis against Infection Antimicrobial Prophylaxis
Antifungal In pts receiving chemo for solid tumors antifungal
prophylaxis may not be beneficial and may ↑ risk of super
infection with resistant fungi
Pts with hematological malignancy and BMT may
benefit more due to longer duration of neutropenia
A. No absorbable antifungal Some have role in oropharayngeal candidiasis but not
invasive fungal infections
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Prophylaxis against Infection Antifungals
B. Systemic antifungals Itraconazole →efficacy in reducing systemic candida
Fluconazole → ↓ superficial and systemic fungal infections in BMT only
Limited spectrum
Inferior to Itraconazole
Amphotericin Effective but more toxic
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Prophylaxis against Infection Antivirals
Pts seropostive for HS and receiving BMT, Acute
leukemia, or past history of infection→acyclovir
prophylaxis during neutropenia
Pts seropostive for varicella and receiving
BMT→acyclovir prophylaxis during neutropenia
BMT→ganciclovir prophylaxis against CMV
during neutropenia.
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Prophylaxis against Infection Antimicrobial Prophylaxis
Recommendation: Routine prophylaxis controversial
May not reduce the need for empiric antimicrobials
Concern about emerging drug-resistant bacteria and
fungi
No consistent reduction in mortality
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