PENATALAKSANAAN

INFEKSI PADA PASIEN

KANKER
 INTRODUCTION
• Infectious complications are a serious cause of morbidity and
mortality in cancer patients,  hematological malignancies.
• Infections  FEVER
• Patients with malignancies are at risk for wide infections – bacterial
infections, fungal infections and viral infections
• Risk factor for infections :
 Underlying immune deficiencies
 Associated comorbidities
 Treatment related adverse effects
 FACTORS PREDISPOSING TO INFECTION IN
CANCER PATIENTS
HOST FACTORS
Disrupted anatomical barriers
Humoral immunodeficiencies
Cell mediated immunodeficiencies
Organ dysfunction
Concurrent illnesses and past infections
Nutritional status
Physhocological stress
TREATMENT ASSOCIATED FACTORS
Surgery or Radiation therapy
Immunosuppressant therapies :
 Chemotherapy
 Biological response modifier
Antimicrobial use
Diagnostic and invasive procedures
 Central Venous Catheter
 Urinary catheters
 Tracheostomy
 Blood transfusions
 HOST ASSOCIATED RISK FACTORS
Host defense mechanisms are mediated by the immune systems
1. The innate (non specifics immune systems)
2. The adaptive (specifics immune systems)
INNATE IMMUNE SYSTEM ADAPTIVE IMMUNE SYSTEM
CHARAC- Discriminates self from non self Discriminates self from non self
TERISTICS General protection Antigens specific
Early phase of host response; Late phase of host response
immediate
Does not require prior exposure Requires prior exposure
Response does not alter on repeated Response improves with
exposure; no memory successive exposure; immuno-
logical memories
 CAUSES OF FEVER
• Infections • Drugs
Caused by bacteria, viruses, • Acute metabolic failures
parasites Thyrotoxicocis crisis
• Immune reactions • Administrations of foreign
Immunological abnormalities, proteins
immune deficiencies • Neoplastic process
• Destructions of tissues trauma, Fever in solid tumor (metas-
local necrosis, rhabdomyolisis tases, necrosis), obstructtions of
• Inflammation ducts, infections
• Self induced fever
 INFECTION IN CANCER PATIENTS
• ESMO Guidelines (European Society of Medical Oncology)
• IDSA Guidelines (The Infectious Disease Society of America)
• NCCN Guidelines (National Comprehensive Cancer Network) in
Oncology
• Bakornas Hompedin 2005/2006:
Panduan Tata laksana Febril Neutropeni/Demam Neutropenia pada
pasien kanker
 ABSOLUTE NEUTROPHIL COUNT (ANC)
• Neutrophils are key components in the systems of
defense against infection
• An absence of neutrophils (neutropenia) 
vulnerable to infection
• After chemotherapy and radiotherapy, the ANC
usually depressed and then slowly rises reflecting
that the bone marrow is recovery
• ANC : the real number of WBC that are neutrophil
• It is derived by multiplying the WBC count times the
percent of neutrophils (the segmented and the band
neutrophil) in the differential WBC count
• Normal = 1500-8000/mm3
 FEBRILE NEUTROPENIA (1)
• Oncologic emergencies
• FN is an oral temperature >38,5◦C or two consecutive reading of >38◦C
for 2 hours and Absolut Neutrophil Count (ANC) <0,5x109/L or
expected to fall bellow 0,5x109/L
• The most concerning complications of cancer chemotherapy
• A major cause of morbidity and delays in chemotherapy
• Elderly patients are at a high risk for febrile neutropenia
 FEBRILE NEUTROPENIA (2)
• Overall mortality rates :
5% (solid tumors); 11% (hematology malignancies)
• Prognosis is worst in patients with proven bacteremia
• Mortality rate of 18 % (Gram negative bacteremia); 5% (Gram positive
bacteremia)
• Mortality varies according to the MASCC (Multinational Association for
Supportive Care) index score
 Mortality rates < 3% if the MASCC score ≥ 21
 Mortality rates >36 % if the MASCC score < 15
 CAUSATIVE PATHOGENS
• Different centres experience different patterns of principal causative
pathogens
• Over the last few decades – a shift has occurred from FN associated to
Gram negative bacteria to Gram positive bacteria
• Positive blood culture  70% are Gram positive organisms
• An increase in antibiotic resistance strains
 Extended Spectrum B lactamase (ESBL) Gram negative bacteria
 Vancomycin resistance Enterococci (VRE)
 Methicillin resistant Staphylococcus Aureus (MRSA)
 INITIAL ASSESSMENT AND INVESTIGATIONS
• Presence of indwelling catheter
• Symptoms or sign suggesting an
infection focus
 Respiratory systems
 Gastrointestinal tracts
 Skin
 Perineal region/ genitourinary
discharge
 Oropharynx
 Central nervous systems
• Previous positive microbiology results
• Routine investigations :
 Blood testing
 Blood culture
 Urinalysis and culture
 Sputum microscopy & culture
 Stool microscopy & culture
 Skin lesion (aspirates/biopsy)
• Further investigations (profound or
prolonged neutropenia) : Chest CT,etc
 MASCC SCORING INDEX (ESMO)
MASCC scoring index
Temperature ≥38.5 ˚C and ANC < 0.5x10 /L 9

Prompt assessment and vigorous CHARACTERISTICS SCORE

Resucitation if needed Burden of illness : no/mild symptoms 5
Burden of illness : moderate symptoms 3
Burden of illness : severe symptoms 0
No hypotension (systolic BP> 90mmHg) 5
Calculate MASCC score No Chronic Obstructive pulmonary Disease 4
Solid tumor/lymphoma with no previous fungal 4
infection
HIGH RISK LOW RISK
No dehydration 3
Outpatient status (at onset of fever) 3
Age < 60 years 2
Inpatient broad spectrum Inpatient oral antibacterial
Intravenous antibacterial therapy for some cases
Scores ≥ 21 are at low risk complication
therapy Points attributed to the variable “burden of illness” are not cumulative
The maximum theoretical score is therefore 26
ESMO Guidelines: Management of febrile nutropenia
 LOW RISK OUPATIENTS
• MASCC score ≥ 21
• Exclusive oral outpatient management for low risk FN is not
supported by high level of evidence
• About 20% cases need re-admission
• Early discharge policy in low-risk cases once they have become
clinically stable , symptomatically better and after there was no fever
minimum 24 hour in hospitals
 LOW RISK INPATIENTS
• Oral antibacterial therapy can be safely substituted for conventional
intravenous treatment in low risk patients
 Who are hemodynamically stable
 Who do not have acute leukemia or evidence of organ failure
 Who do not have pneumonia
 Who do not have an indwelling catheter
 Who do not have a severe soft tissue infection
• Single agent quinolones were not inferior to combinations (quinolone +
amoxicillin-clavulanic acid)
• Oral quinolone should not be used in patients who use it as prophylaxis
 HIGH RISK PATIENTS
• Local epidemiological bacterial isolate & resistance patterns
• Pnemonia
Antibiotic cover must be extended to treat atypical organism such as Legionella
and Mycoplasma by adding a macrolide antibiotic to B lactam antibiotic (V,D)
• Pneumocytis infection  High dose cotrimoxazole (I,A)
• Cellulitis  The addition of Vancomycin broadens the cover against skin
pathogen
• Intrabdominal infection/sepsis: metronidazole should recommended (V,D)
• Diarrhea : Assetment of Clostridium difficile is needed and treatment with
metronidazole if suspected
HIGH RISK PATIENTS : CENTRAL IV CATHETER INFECTION (CRI)
• If CRI is suspected  culture from both catheter and peripherally
• When CRI is suspected & the patient is stable  the catheter should not
be removed without microbiological evidence of infection
A glycopeptide (Vancomycin) should be administered through the line when
possible to cover Gram positive organism (III,A)
Teicoplanin is a useful alternative
• In CRI due to Coagulase Negative Staphylococcus (CNS)  preserving the
catheter can be made when patient is stable
• Removal of the catheter is indicated  tunnel infections, pocket infections
(implanted port systems), persistent bacteremia despite adequate
treatment, atypical mycobacterial infection, candidemia
 ASSESSMENT OF RESPONSE & SUBSEQUENT MANAGEMENT
Review of therapy at 48 hours

Patient apyrexia and ANC ≥0.5x109/L Pyrexia continue

Patient stable : Patient deteriorating :

Continue same therapy Seek expert advice from
ID physician or clinical
microbiologist

LOW RISK HIGH RISK

On oral antibacterial: On IV antibacterial: Pathogen not identified: Pathogen identified:

Continue therapy & con- Considering continuing Discontinue aminoglycoside, Consider specific antibacterial
sider early discharge therapy with oral anti- Continue IV therapy therapy
bacterial
FEBRILE NEUTROPENIA
Fever (≥ 38.3˚C) and Neutropenia (≤ 0.5x109 cells/L)
IDSA 2011 GUIDELINES
…
LOW RISK HIGH RISK
• Anticipated neutropenia ≤ 7 days • Anticipated neutropenia > 7 days
• Clinically stable, • Clinically stable,
• No medical comorbidities • Any medical comorbidities

OUPATIENT ANTIBIOITIC INPATIENT IV ANTIBIOITIC INPATIENT IV ANTIBIOITIC

• Oral regimen if able to tolerate & • Documented infection requiring Empiric antibiotic monotherapy (any
absorb IV antibiotics of the following)
• Availability of caregiver, telephone, • Gastrointestinal intolerance • Piperacilin tazobactam OR
transportation • Patient & physician decision • Carbapenem OR
• Patient & physician decision • Ceftazidim OR
• Cefepim
If responding and criteria met for
Oral ciprofloxacin +
outpatient management
amoxicillin/clavulanat
Adjust antimicrobial based on specific clinical, radiograph, and/or
culture data. Example :
• Vancomycin or Linezolid for cellulitis or pneumonia
Observe 4-24 hours in clinic to ensure that empiric • Add aminoglycoside and switch to carbapenem for pneumonia or
antibiotics are tolerated and patients remains stable Gram negative bacteremia
prior to discharge for outpatient therapy • Metronidazole for abdominal symptoms or suspected C. difficile
infection