Febrile Neutropenia 2

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Information about Febrile Neutropenia 2
Science-Technology

Published on January 12, 2009

Author: aSGuest10195

Source: authorstream.com

Febrile Neutropenia : Febrile Neutropenia SIRIPORN PHONGJITSIRI Febrile Neutropenia : 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? Febrile Neutropenia : 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? Febrile Neutropenia : Febrile Neutropenia Bacterial infection Neutropenia :single most important risk factor for infection in cancer pts. Risk of infection increases 10-fold with declining neutrophil counts < 500/mm3 48-60% : occult infection 16-20% with neutropenia<100/mm3 have bacteremia Initial Empiric AntibioticsRationale : Initial Empiric AntibioticsRationale Severe risk of bacterial sepsis Insensitivity of diagnostic tests Delays in identification of pathogens Febrile Neutropenia : 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? Febrile NeutropeniaLevel of Fever & Neutropenia : Febrile NeutropeniaLevel of Fever & Neutropenia Fever : single oral temp. > 38.3 0C or a temp. >38.0 0C for > 1 hr Neutropenia : neutrophil count < 500 /mm3 , or a count of < 1,000 with a predicted decrease to < 500 Febrile NeutropeniaEvaluation : Febrile NeutropeniaEvaluation History Physical examination : minimal signs Risk assessment Investigations Possible sites of infection : Possible sites of infection URTI Dental sepsis Mouth ulcers Skin sores Exit site of central venous catheters Anal fissures GI Preantibiotic Investigations : Preantibiotic Investigations Blood C/S : central line & peripheral Chest X-Ray Urine C/S Stool C/S Biopsy cultures Viral studies Febrile Neutropenia : 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? Initial Empiric AntibioticsConsiderations : 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 Febrile NeutropeniaBacterial causes (EORTC) : Febrile NeutropeniaBacterial causes (EORTC) Gram-positive bacteria (60-70%) Gram-negative bacilli (30-40%) Gram-positive Bacteria : Gram-positive Bacteria Staphylococcus spp : MSSA,MRSA, Streptococcus spp : viridans Enterococcus faecalis/faecium Corynebacterium spp Bacillus spp Stomatococcus mucilaginosus Gram-negative Bacteria : Gram-negative Bacteria Escherichia coli Klebsiella spp : ESBL Pseudomonas aeruginosa Enterobacter spp Acinetobacter spp Citrobacter spp Stenotrophomonas maltophilia Anerobic Bacteria : Anerobic Bacteria Bacteroides spp Clostridium spp Fusobacterium spp Propionibacterium spp Peptococcus spp Veillonella spp Peptostreptococcus spp Slide 17: 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 microbiological documented gr. Siriluck Anunnatsiri,M.D. Slide 18: Retrospective reviewed trend of bacterial infection of children with admitted in Ramathibodi 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 Initial Empiric AntibioticsRecommended choices : Initial Empiric AntibioticsRecommended choices Monotherapy Duotherapy without vancomycin Vancomycin plus one or two drugs :  Low risk hospitalized febrile neutropenia pts.were assigned to receive either an oral regimen(amoxicillin-clavulanate plus ciprofloxacin) or IV ceftazidime. The success rate was 71% in the oral regimen and 67% in IV gr. Freifeld A et al. N Engl J Med.1999;341:305-311 Kern WV et al. N Engl J Med.1999;341:312-318 : Kern WV et al. N Engl J Med.1999;341:312-318 Low risk adults and a very small number of children with febrile neutropenia were enrolled. Treatment was successful in 86% of pts.treated with oral therapy (ciprofloxacin + amoxicillin-clavulanate) and 84% of those in IV gr.(ceftriaxone + amikacin) Oral Antibiotics and Outpatient Management : Oral Antibiotics and Outpatient Management Current studies : potentially be safe and effective in low-risk patients Febrile NeutropeniaLow Risk : Febrile NeutropeniaLow Risk ANC > 100 /mm3 Normal CXR Duration of neutropenia < 7 d Resolution of neutropenia <10 d No appearance of illness No comorbidity complications Malignancy in remission Monotherapy Choices : Monotherapy Choices Ceph 3 : ceftazidime Ceph 4 : cefepime Carbapenem : imipenem , meropenem IDSA guidelines-2002 Combination TherapyAdvantages : Combination TherapyAdvantages Increased bactericidal activity Potential synergistic effects Broader antibacterial spectrum Limits emergence of resistance Combination TherapyDisadvantages : Combination TherapyDisadvantages Drug toxicities Drug interactions Potential cost increase Administration time Combination TherapyChoices : Combination TherapyChoices Aminoglycoside + Anti-pseudomonal carboxypenicillin Aminoglycoside + Anti-pseudomonal cephalosporin Aminoglycoside + Carbapenem Vancomycin as Empiric RxWhen to use ? : 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 Febrile Neutropenia : 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? Initial Antibiotic ModificationsConsiderations : Initial Antibiotic ModificationsConsiderations Persistence of fever Clinical deterioration Culture results Drug intolerance/side effects Persistent FeverCauses : Persistent FeverCauses Nonbacterial infection Resistant bacteria Slow response to antibiotics Fungal sepsis Inadequate serum & tissue levels Drug fever Persistent Fever > 5 DaysChoices of Mx : Persistent Fever > 5 DaysChoices of Mx Continue initial Rx Change or add antibiotics Add an antifungal drug(Ampho B) Febrile Neutropenia : 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? Duration of Antibiotic TherapyWhen to stop? : 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 Febrile NeutropeniaConclusions : Febrile NeutropeniaConclusions Significant morbidity & mortality Choice of initial empiric therapy dependent on epidemiologic & clinical factors Monotherapy as efficacious as combination Rx Modifications upon reassessment Duration dependent on ANC

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