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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





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





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





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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



What is appropriate initial Rx?

How should initial Rx be modified?


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



What is appropriate initial Rx?

How should initial Rx be modified?


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

febrile neutropenia 2

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