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8/3/2019 Febrile Neutropenia 2
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Febrile Neutropenia
SIRIPORN PHONGJITSIRI
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx? How should initial Rx be modified?
How long should empirical Rx be
continued?
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx? How should initial Rx be modified?
How long should empirical Rx be
continued?
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Febrile Neutropenia
Bacterial infection
Neutropenia :single most important riskfactor for infection in cancer pts.
Risk of infection increases 10-fold withdeclining neutrophil counts < 500/mm3
48-60% : occult infection
16-20% with neutropenia
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Initial Empiric AntibioticsRationale
Severe risk of bacterial sepsis
Insensitivity of diagnostic tests
Delays in identification of pathogens
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx? How should initial Rx be modified?
How long should empirical Rx be
continued?
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Febrile NeutropeniaLevel of Fever & Neutropenia
Fever : single oral temp. > 38.30C or a
temp.>38.00
C for> 1
hr
Neutropenia : neutrophil count < 500 /mm3
, or a count of < 1,000 with a predicted
decrease to < 500
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Febrile NeutropeniaEvaluation
History
Physical examination : minimal signs
Risk assessment Investigations
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Possible sites of infection
URTI
Dental sepsis
Mouth ulcers Skin sores
Exit site of central venous catheters
Anal fissures GI
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Preantibiotic Investigations
Blood C/S : central line & peripheral Chest X-Ray
Urine C/S
Stool C/S
Biopsy cultures Viral studies
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx? How should initial Rx be modified?
How long should empirical Rx be
continued?
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Initial Empiric AntibioticsConsiderations
Broad spectrum of bactericidal activity
Local prevalence, susceptibility pattern
Antibiotic toxicity : well-tolerated, allergy
Host factors : severity of presentation
Prior antibiotic usage
Antibiotic costs
Ease of administration
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Febrile NeutropeniaBacterial causes (EORTC)
Gram-positive bacteria (60-70%)
Gram-negative bacilli (30-
40%)
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Gram-positive Bacteria
Staphylococcus spp :MSSA,MRSA,
Streptococcus spp : viridans
Enterococcus faecalis/faecium
Corynebacterium spp
Bacillus spp Stomatococcus mucilaginosus
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Gram-negative Bacteria
Escherichia coli
Klebsiella spp : ESBL
Pseudomonas aeruginosa Enterobacter spp
Acinetobacter spp
Citrobacter spp
Stenotrophomonas maltophilia
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Retrospective study in Srinagarin Hospital Reviewed febrile neutropenia adult pts. with
hematologic malignancy illness 18% FUO which may associated with
underlying disease 36% UTI
25% skin & soft tissue infection 21% bacteremia Pathogens : K. pneumoniae , E. coli ,
Pseudomonas aeruginosa , Acinetobacter spp. ,Staphylococcus
Mortality rate 24% higher in microbiologicaldocumented gr.
Siriluck Anunnatsiri,M.D.
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Retrospective reviewed trend of bacterial
infection of children with admitted inRamathibodi hospital 89 pts.
The incidence of positive culture was
13.6% Most of the organism isolated were
Salmonella sp. 21% , K. pneumoniae 16%
and P. aeruginosa 10.5%Punpanich W, et al. Thai J Pediatr 1999;38:9-16
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Initial Empiric AntibioticsRecommended choices
Monotherapy
Duotherapy without vancomycin Vancomycin plus one or two drugs
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Low risk hospitalized febrile neutropenia
pts.were assigned to receive either an oralregimen(amoxicillin-clavulanate plusciprofloxacin) or IV ceftazidime. The
success rate was 71% in the oral regimenand 67% in IV gr.
Freifeld A et al. N Engl J Med.1999;341:305-311
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Kern WV et al. N Engl J Med.1999;341:312-318
Low risk adults and a very small number of
children with febrile neutropeniawereenrolled. Treatment was successful in86% of pts.treated with oral therapy(ciprofloxacin + amoxicillin-clavulanate)and 84% of those in IV gr.(ceftriaxone +amikacin)
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Oral Antibiotics and OutpatientManagement
Current studies : potentially be safe
and effective in low-risk patients
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Febrile NeutropeniaLow Risk
ANC > 100 /mm3
Normal CXR
Duration of neutropenia < 7 d Resolution of neutropenia
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MonotherapyChoices
Ceph 3 : ceftazidime
Ceph 4 : cefepime
Carbapenem : imipenem , meropenem
IDSA guidelines-2002
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Combination TherapyAdvantages
Increased bactericidal activity
Potential synergistic effects
Broader antibacterial spectrum
Limits emergence of resistance
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Combination TherapyDisadvantages
Drug toxicities
Drug interactions
Potential cost increase
Administration time
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Combination TherapyChoices
Aminoglycoside + Anti-pseudomonalcarboxypenicillin
Aminoglycoside + Anti-pseudomonalcephalosporin
Aminoglycoside + Carbapenem
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Vancomycin as Empiric RxWhen to use ?
Known colonization with MRSA or PRSP
Clinically suspected serious catheter-
related infections (eg bacteremia) Hypotension or cardiovascular impairment
Initial positive results of blood culture for
G+ bacteria
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx?
How should initial Rx be modified?
How long should empirical Rx be
continued?
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Initial Antibiotic ModificationsConsiderations
Persistence of fever
Clinical deterioration
Culture results
Drug intolerance/side effects
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Persistent FeverCauses
Nonbacterial infection
Resistant bacteria
Slow response to antibiotics Fungal sepsis
Inadequate serum & tissue levels
Drug fever
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Persistent Fever > 5 Days
Choices of Mx
Continue initial Rx
Change or add antibiotics
Add an antifungal drug(Ampho B)
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Febrile Neutropenia
Who should receive empirical Rx?
When should empirical Rx be started?
What is appropriate initial Rx?
How should initial Rx be modified?
How long should empirical Rx be
continued?
D i f A ibi i Th
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Duration of Antibiotic TherapyWhen to stop?
No infection identified after 3 days of Rx
ANC > 500 for 2 consecutive days
Afebrile > 48 hr
Clinically well
F b il N i
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Febrile NeutropeniaConclusions
Significant morbidity & mortality
Choice of initial empiric therapy dependenton epidemiologic & clinical factors
Monotherapy as efficacious ascombination Rx
Modifications upon reassessment
Duration dependent on ANC