2. INTRODUCTION
• Most common emergency encountered in children on
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treatment for a malignancy
Significant cause of morbidity & mortality
Occurs in children diagnosed to have a/c
leukemia,lymphoma,solid tumor or aplastic anemia
It may result from underlying malignancy per se or
typically due to effect of chemotherapy
Fever may be the sole manifestation
3. • Definition: a single oral temp of ≥38.3˚C(101˚F) or a
temp of ≥ 38.0˚C(100.4˚F) for ≥ 1 hour, with an absolute
neutrophil count(ANC=mature granulocytes+neutrophil
band or stab cells) of <500/mm3, or an ANC is expected
to decrease to <500cells/mm3 during the next 48 hrs.
• Profound neutropenia- ANC < 100cells/mm3
• Prolonged neutropenia- neutropenia lasting >7days
4. EVALUATION
• History: should include following points:
• Fever onset,duration & severity
• Asso. localizing symptoms: ear, nose, throat, respiratory,
gastrointestinal, musculoskeletal and urinary system
• Phase of chemotherapy(intensive or non intensive)
• Duration since last chemotherapy
• Recent hospitalizations & antibiotic received, if any.
6. • Majority of infections in febrile neutropenia are caused by
gram negative organisms,eg: pseudomonas aeruginosa,
E.Coli, klebsiella pneumonia, acinetobacter species
• Common gram positive organisms are staphylococcus
aureus, coagulase negative staphylococcus &
enterococcus
• Common Fungal infections are candida, aspergillus, or
mucor
7. INVESTIGATIONS
• First line investigations:
• Complete blood count, including differential leukocyte
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count & ANC
Serum electrolytes, urea & creatinine
Blood culture: before administration of antibiotics. Two
sets of blood cultures from separate venepuncture sites
Chest radiograph: in patients with respiratory symptoms &
signs
Cultures from any other site, as clinically relevant: stool,
urine, csf, skin, respiratory secretions ,pus.
8. • Second line investigations:
• Serum Galactomannan test, CT Scan of chest/ paranasal
sinuses may be indicated in patients with suspected
fungal infection
• Bronchoalveolar lavage: if pneumonia is non-resolving or
non responding
• Skin biopsy ,from skin nodules, if any.
9. RISK STRATIFICATION
• Low risk patients:
• Clinically stable & well looking
• Temperature <39˚ C
• Non-intensive phase of chemotherapy
• Malignancy in remission
• Lack of any focus of infection, eg: pneumonia,abscess,
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sinusitis or diarrhoea
Lack of medical comorbidities
ANC ≥ 100/mm3 & likely to rise within the next 7 days
Absolute monocyte count > 100/mm3
Not fulfilling any criteria for high risk category
10. • High risk patients:
• Recent intensive chemotherapy
• Profound neutropenia( ANC < 100cells/mm3) , anticipated
to extend for > 7days
• Any focus of infection,eg: cellulitis, abscess, pnemonia,
diarrhoea
• Evidence of hypotension, respiratory distress or
hypoxemia
• Mucositis interfering with oral intake or resulting in
diarrhoea
12. MANAGEMENT
• High risk patients are to be hospitalized & administered
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broad spectrum i.v. antibiotics
Knowledge of locally prevailing bacteriological profile &
antimicrobial susceptibility data is crucial for choice of
antibiotics
Antibiotics:
It is important to administer first dose of antibiotics without
any delay. Delay in initiating antibiotics significantly
increases the morbidity & mortality
Caretakers are advised not to administer paracetamol at
home as it may mask fever & lead to delay seeking
medical care
13. • Anti-pseudomonal β-lactam agents:
• Monotherapy with anti-pseudomonal β-lactam agents
such as anti-pseudomonas penicillin(piperacillintazobactum), anti-pseudomonal
cephalosporin(cefoperazone-sulbactum) or
carbapenems(meropenem or imipinem-cilastatin) or
cefipime is recommended as first line by Infectious
Disease Society of America.
• Carbapenems can be reserved as second line antibiotics
to prevent the emergence of drug resistant organisms.
• Colistin is reserved as third line drug.
14. • In hemodynamically unstable patient, an adequate
coverage for drug resistant gram negative & gram positive
organisms as well as for anaerobes should be given
• hence, second line drugs should be administered upfront
• Combination of anti-pseudomonal carbapenem, as well as
addition of an aminoglycoside, together with vancomycin
provides this cover.
• Specific gram positive cover is added only if patient has
evidence of any of the following:
-Hemodynamic instability
-Severe sepsis
-Radiographically confirmed pneumonia
15. -Clinically suspected catheter related infection
-Skin or soft tissue infection
-Known colonisation with MRSA, Vancomycin
resistant enterococcus(VRE), Penicillin resistant
streptococcus
-Severe mucositis, if fluroquinolone prophylaxis has
been given & ceftazidime is employed as emperical
therapy
• Emperical or presumptive anti-malarial therapy is not
recommended.
16. GENERAL CONSIDERATIONS &
SUPPORTIVE CARE
• Pro-active steps must be taken to reduce incidence of
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hospital acqired sepsis
Use of alcohol based handrub in between patients must
be ensured by each medical & nursing personnel
Use of iv fluids, central line, foleys catheter,etc must be
restricted if possible
Administration of iv fluids for minor reasons should be
avoided
Nasogastric feeding is encouraged in patients with
anorexia or mucositis
Rectal enemas,suppositories & rectal examinations are
contraindicated in neutropenic patients
17. • Non-invasive intermittent positive pressure ventilation
should be attempted in case of a/c respiratory failure
• Hemoglobin < 8g/dl is generally an indication for blood
transfusion in a stable patient
• Indication for platelet transfusion: in a stable patient
without any comorbidities and bleeds, prophylactic
transfusions are recommended at a count below
10000. transfusion threshold of 20000 recommended in
patients with minor bleeds(mucosal,epistaxis) and 1,00,000
in major bleeds(hemoptysis, GI, or CNS bleeds)
18. • Growth factors: administration of G-CSF has no role in
management of children with uncomplicated febrile
neutropenia. Might be useful in reducing duration of
neutropenia & length of hospital stay in children with
complicated febrile neutropenia(pneumonia, hypotension,
invasive fungal infection, multiorgan dysfunction)
19. SUBSEQUENT MANAGEMENT
• Patient who is without a focus of infection, afebrile within 2-
3days of first line antibiotics, along with a rising ANC, with
negative cultures, may be discharged after 24-48hrs or may be
shifted to oral antibiotics, till ANC exceeds 500/cumm
• In case of documented infections, including soft tissue
infection, pneumonia or bacterimia, appropriate antibiotics
should be given for 10-14days
• Persistent fever beyond 3days, despite antibiotic therapy
should prompt a thorough search for source of infection:
-relevant investigations include repeat blood/urine
cultures,stool for clostridium difficle,fungus & atypical
organisms in case of diarrhea & CT Scan of chest/sinuses
20. -antibacterials should be upgraded in high risk patients
with persistent fever after 48-72hrs, or earlier in case of
any hemodynamic instability
-empirical antifungal therapy(Amphotericin) and
investigations for invasive fungal infections should be
considered for patients with persistent or recurrent
fever after 4-7days of antibiotics and whose overall
duration of neutropenia is expected to exceed 7days
