Complications related to Treatment of Leukemia Fever and Neutropenia Aziza Shad, MD Lombardi Cancer...
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Transcript of Complications related to Treatment of Leukemia Fever and Neutropenia Aziza Shad, MD Lombardi Cancer...
Complications related to Treatment of
Leukemia ‘Fever and Neutropenia’
Aziza Shad, MDLombardi Cancer CenterGeorgetown University HospitalWashington DC
Mortality Associated with Infection during
Neutropenia
0
20
40
60
80
100
1950 1960 1970 1980 1990 2000
Empirical therapy
Mort
al it
y r
ate
Factors involved in decreasing mortality
•Empirical antibiotic therapy
•Supportive care strategies
• Infection control strategies
Principles of Empiric Antibiotic Therapy
1. Recognition of commonly occurring pathogens, link between specific pathogens and specific sites, drug and/or tumor, tumor-related barrier breakdown
2. Broad coverage directed against the most common pathogenic organisms
Principles of Empiric Antibiotic Therapy
3. Prevention of development of multi-resistant organisms
4. Hold the fort until the underlying lesion is corrected by the return of neutrophils
Definitions
• Fever: single oral temperature of > 38.3 °C (101 °F) or > 38 °C (100.4 °F) for more than 1 hour.
• Neutropenia: ANC <500cells/mm3 or ANC <1000 cells/mm3 with a predicted decrease to <500 cells/mm3
CID 2002, 34:730-751
Recognition of potential pathogens
Evaluation of the host
• Diminished inflammatory response alters usual signs and symptoms of infection
• Fever may be the earliest warning sign
• Absence of fever in patient with localizing signs, even if subtle, may point to infection
Cancer
Treatment
Nutritional status
Microbialflora
Humoral + cellular immunity
Phagocytic defenses
REsystem
Skin + mucosalbarriers
Recognition of potential pathogens
Mouth: gingiva, dentition, buccal mucosa--gram+ anaerobes/HSV/ Candida
Skin: BMA/B, LP, venipuncture sites, tissue around nails - gram+/ fungal / Pseudomonas/VZV
Abdomen/perianal area:enterococci/gram-/anaerobes
Central Catheter:gram+/-
Pulmonary: bacteria, PCP, virus, fungi
Diarrhea: C. difficile
Even with a comprehensive evaluation, an infectious etiology is demonstrated in 50 to 70% of cases
Recognition of potential pathogens
• All efforts should be made in order to identify a pathogen
• Focal findings should be investigated + cultures should be sent when possible
• If no focus send BC/UC
• Determine whether vancomycin is needed
Evaluation of the host
Blood Cultures
If CVC is present culture all ports - 33% oftimes only one port is positive
Peripheral blood cultures when CVC is present is controversial and may not contribute to the management of the pediatric patient
Blood cultures should be sent at least daily if patient remains febrile
Broad coverage against the most common
organisms85-90% of isolated pathogens during new
fever in a neutropenic patient are bacteria
Gram + and Gram - bacteria. Endogenous flora / nosocomial flora
The relative distribution of these organisms vary among institutions
Antibiotic sensitivity patterns vary among institutions
Bacterial Causes during F/N
I ndustrialized Countries
Gram- positive cocci and bacilli *60- 70% of isolates Staphylococcus spp
Coagulase –negative Coagulase-positive Streptococcus spp Enterococcus spp Corynebacterium spp
Developing Countries
Gram- positive cocci and bacilli Staphylococcus spp
Coagulase-positive Coagulase-negative
Gram- negative cocci and bacilli Escherichia coli Klebsiella spp Pseudomonas aeruginosa
Gram- negative cocci and bacilli *60- 70% of isolates
Pseudomonas aeruginosa Escherichia coli Klebsiella spp
Anaerobes Bacteroides spp Clostridium spp Fusobacterium spp Peptococcus/ peptostreptococcus spp Veilonella spp
Bacterial Causes during F/N
Use of central vascular devices Nutritional status Intestinal Parasitosis Infection control strategies 60 % of hospital-acquired infections are caused by
drug resistant microbes in industrialized countries this is many times unknown in developing countries
Disparities between Nations: potential explanations
Emergence of Antimicrobial Resistant Bacteria
Hospital-acquired
Community-acquired
1950 1960 1970 1980 1990
S. aureus
Gram - rods
Enterococcus spp
S pneumoniae
H. influenzae
N. gonorrhoeae
M. catarrhalis
Shigella spp
Emergence of Antimicrobial Resistant Bacteria
Gram-positive cocci
• The most recent of which are VRE• MRSA are no longer confined to hospital wards• 90 % of strains of S.aureus are resistant to
penicillin• Prevalence of DRSP shows geographic variation
30- 40%
Emergence of Antimicrobial Resistant Bacteria
Gram-negative bacilli
• ESBL are enzymes that mediate resistance to third generation cephalosporins and monobactams but do not affect cephamycins or carbapenems
• Common ESBL producers are E. coli, Klebsiella spp, P.aeruginosa and enterobacteria
Cause more indolent infectionsThe most common isolates (CNS, VRE, Corynebacterium jk)
Cause acute infections that progress rapidly S.aureus, S.viridans, pneumococcus also
Cause usually superinfections
M onotherapyCef t az id ime
Cef epime or
Car bapenems
T wo Drugs+ A minoglycos ide
or
2 lac t ams
Vancomycinnot needed
Vancomycin plusCephs / car bap
+/ -
aminoglycos ide
Vancomycinneeded
ff ff ff ff ff ff ff ff ff ff ff ff ff
Child with Fever + N eutropeniaff ff ff ff ff ff ff ff ff ff ff ff ff ff ff
Reassess after 3-5 days
• BC gram + cocci in clusters• Known MRSA colonization• CVL tunnel infection• Suspected sepsis• Substantial mucosal damage• Prophylaxis with quinolones• Sudden increase in temp >40°C
Selection of initial antibiotic therapy
Antibiotic Enteric Gram –P. Aeruginosa
CPS/CNS
Entero cocci
Strepto- cocci
Anaerobes
CeftazidimeCefoperazone
+++ ++/- - - -
Cefepime +++ ++/- - + +
ImipenemMeropenem
+++ +++/+
+++ +++ +++
Quinolones +++ +++/+
+++ + +++
AztreonamAminoglycoside
+++ -/- - - -
Ticar/TazoPiper/clavul
+++ +++/+
+++ + +++
Antibiotic Enteric Gram –P. Aeruginosa
CPS/CNS
Entero cocci
Strepto- cocci
Anaerobes
CeftazidimeCefoperazone
+++ ++/- - - -
Cefepime +++ ++/- - + +
ImipenemMeropenem
+++ +++/+
+++ +++ +++
Quinolones +++ +++/+
+++ + +++
AztreonamAminoglycoside
+++ -/- - - -
Ticar/TazoPiper/clavul
Higher incidence of C. diff colitis/ N+V/ seizures
Good efficacy
More gram positive infections detected
Good efficacy and tolerance
Usually in prophylaxis during neutropenia in high risk patients
Use in lactams allergy – only in combinationToxicity – use only in combination
Limited experience – interfere with Aspergillus antigen detection
Reassessment – Afebrile patient
ConsiderPO ant ibiot ics
Low Risk
Cont inue sameI V ant ibiot ics
H igh r isk
N o et iology
A dj usttherapy
Et iology ident ifi ed
ff ff ff ff ff ff ff ff ff ff ff ff ffA f ebr ile within the fi rst 3- 5 days of t reatment
ff ff ff ff ff ff ff ff ff ff ff ff ff ff ff
Sequential Oral antibiotics
• Limited experience
• Significant cost reduction
• Only for low-risk patients
• Less tolerance (GI toxicity)
• Antibiotic Regimens:
Ciprofloxacin Cipro + amoxi-clavulanic
Factors that favor a Low Risk for severe infections during Neutropenia
ANC > 100 cells/mm3 AMC >100 cells/mm3 Normal CXR Nearly normal renal and lever function tests Duration of neutropenia < 10 days No CVL infection Malignancy in remission Peak temperature <39 °C No neurological or mental status changes No abdominal pain No appearance of illness No co-morbidity complications
Lab
ora
tory
Clin
ical
Reassessment – Febrile Patient
I f no changein pat ientcondit ion
D/ C vanco
Cont inue sameA nt ibiot ics
CoverES BL T ype 1 lactamase
I f progressivedisease
I f cr iter ia f orVancomycin
Change A nt ibiot ics A dd ant if ungaldrug
ff ff ff ff ff ff ff ff ff ff ff ff ffFebrile f or the fi rst 3- 5 days of t reatment
O r new onset f ever
• Review all cultures
• Meticulous Physical exam
• CXR- Image any organ suspected of having infection (CT/US)
• Status of CVL/PIV or venipuncture site
• Pursue biopsy / culture of affected areas / BAL
• Send Aspergillus galactomannan
S ubsequent T herapy
Days 3- 7
I nit ial T herapy
Day 1
I nit ial Evaluat ion
ttt
Approach to the febrileneutropenic patient
Summary
History - Physical examCXR-UC-BCbp + cx of suspicious lesions
Empiric broad spectrum antibiotics
Documented infection
Fever unknown origin
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Factors involved in decreasing mortality
•Supportive care strategies
• Infection control strategies