This document provides an overview of the management of neutropenic fever in pediatric patients. It defines febrile neutropenia and outlines the etiology, clinical manifestations, investigations, and risk stratification approach. Common pathogens include gram-negative bacteria like Klebsiella pneumoniae and Escherichia coli. Investigations include blood cultures, urine analysis and culture if indicated, and chest x-ray only for symptomatic patients. Risk stratification divides patients into high-risk and low-risk categories based on factors like symptoms, anticipated neutropenia duration, and underlying condition. High-risk patients require hospital admission.

1. Management of Neutropenic fever
Dr. G/yesus E.
Moderator : Dr. G/Hiwot (Pediatrician)
1-Apr-23 1
Febrile neutropenia

2. Presentation Out lines
• Introduction
• Definition
• Etiology of fever
• Clinical manifestations
• Approach Neutropenic fever
• Investigations
• Risk stratification
• Management
• Modified Guideline for ACSH
1-Apr-23 Febrile neutropenia 2

3. Questions
• What clinical features and laboratory markers can be used to classify FN ?
• What clinical, laboratory, and imaging studies are useful at the initial
presentation of FN?
• What empirical antibiotics are appropriate for children with high-risk FN?
• When and how should the initial empirical antibiotic therapy be modified ?
• When can empirical antibiotics be discontinued in low- and high-risk FN?
1-Apr-23 Febrile neutropenia 3

4. Introduction
• Infection is a major cause of morbidity and mortality in cancer patients.
• Fever may be the first manifestation of a life-threatening infection, particularly
during periods of neutropenia.
• Febrile episodes occur in approximately one-third of Neutropenic episodes in
children with chemotherapy-induced neutropenia or after hematopoietic cell
transplantation .
Up-to-date,2018
1-Apr-23 Febrile neutropenia 4

5. Introduction …
• Fever occurs frequently during chemotherapy-induced neutropenia:
• 10%–50% of patients with solid tumors
• >80% hematologic malignancies with >/=1chemotherapy cycle associated with
neutropenia
• Most patients will have not documented infectious etiology.
• Clinically documented infections ~ 20%–30%.
• Bacteremia occurs in 10%–25% of all patients.
• Most episodes occur in prolonged or profound neutropenia (ANC<100 ne/mm)
• common sites of tissue-based infection include the intestinal tract, lung, and skin.
• Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with
Cancer , IDSA, 2010
1-Apr-23 Febrile neutropenia 5

6. Introduction …..
• In a 2yr retrospective study of 226 cancer patients in ACSH 2018-20
• 55 episodes of FN among 40 oncologic patients were analyzed
• Hematologic malignancy 96.3% of episodes
• Febrile neutropenia was common in descending order
• Lymphocytic leukemia, AML, NHL, brain tumor ,HL and retinoblastoma
respectively
• Common during induction and consolidation
Kiros T. Treatment outcome and associated factors of febrile neutropenia among pediatric
patients with cancer in ACSH, Northern Ethiopia,sep,2020.
1-Apr-23 Febrile neutropenia 6

7. Definitions
• Fever is defined as a single oral temperature >/= 38.3°C or oral temperature >/=
38°C for 1 hour or more.
• Oral temperatures are preferred.
• However, when axillary temperatures are the only option, fever is defined as a
single axillary temperature of >/= 37.8°C or axillary temperature >/= 37.5°C for 1
hour or more.
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8. Definition …
• Neutropenia
• Neutropenia is defined as an absolute neutrophil count (ANC) <1500 cells/mm3
• Neutropenia
• ANC of <500 cells/mm3 or an
• ANC that is expected to decrease to <500 cells/mm 3 in the next 48 h
• Profound neutropenia: ANC is <100 cells/mm 3
• The ANC is calculated using the following formula:
ANC = total WBC count (cells/ cells/mm3 ) x (percent neutrophils + % bands) ÷ 100
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9. Introduction …
• First Neutropenic fever: first febrile episode occurring during a given period of
chemotherapy-induced neutropenia
• Persistent Neutropenic fever:
• a febrile episode without defervescence after at least 5 days of initial empiric
broad-spectrum antibacterial therapy in high-risk Neutropenic patients
• Recrudescent fever: febrile episode that recurs following initial defervescence
during a course of broad-spectrum antibacterial therapy
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10. Introduction …
• Neutropenic fever syndromes
• The International Immunocompromised Host Society has classified initial Neutropenic fever
syndromes into three categories .
• Microbiologically documented infection ( 10-20%)
• Neutropenic fever with a clinical focus of infection and an associated pathogen
• Clinically documented infection ( 20-30%)
• Neutropenic fever with a clinical focus (cellulites)
• No isolated pathogen
• Unexplained fever (50-60%)
• Neutropenic fever without clinical focus or identified pathogen
Up-to-date ,2018
1-Apr-23 Febrile neutropenia 10

11. Etiology of fever
• The etiology of initial fever may be non-infectious, bacterial, viral or less
commonly due to other pathogens.
• Viral pathogens are common and evaluation should be directed at specific
signs and symptoms.
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12. 1950s &early
1960s
• Common pathogens were gram-positive organisms,
Late 1960s
&1970s • Common pathogens were gram-negative organisms- E.coli, Klebsiella, Pseudomonas sp.
1980s • TMP/SMZ started being used for prophylaxis in neutropenic patient
1990
• IDSA Guidelines recommended TMP/SMZ for patients with profound neutropenia for > 1 weeks
• Common pathogens -gram-positives (e.g .s. aureus, & gram- negatives (E. coli, Pseudomonas sp.)
• early 1990s, the increased use of fluoroquinolones for prophylaxis in neutropenic patients began.
1997&
2002
• IDSA Guidelines did not recommend the routine use of TMP/SMZ or quinolones for prophylaxis.
2010
• Increase in drug-resistant pathogens ~ MRSA, VRE, ESBL-producing Enterbacteriaciae
• IDSA Guidelines recommended the use of fluoroquinolones in high-risk patients with prolonged and profound neutropenia
1-Apr-23 12
Febrile neutropenia

13. Etiology of fever…
• ETIOLOGY OF FEVER
• The rate of documented infection, when a child presents with fever and
therapy-induced neutropenia, ranges between 10 and 40 percent.
• No clinical or microbiologic evidence of infection will be established in the
remainder.
• Bacteremia is the most common form of documented infection (20 to 50 %)
• Other sites of infection
• GIT oral or intestinal mucositis or diarrhea caused by Clostridium
difficile and Salmonella spp
• Upper and lower respiratory tract
• Urinary tract
• Skin and soft tissues
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14. Etiology of fever…
• In a 2yr retrospective study of 226 cancer patients in ACSH 2018-20
• 55 episodes of FN among 40 oncologic patients were analyzed
• 17 pathogen was isolated
• Most of isolated bacteria were gram negatives ~ 88.2 %
• ESBL positive ~ 40%
• Klebsiella pneumonia
• Escherichia coli
• Enterobacter cloacae
• Acinobacter species
• Microbiological confirmed FN -27.2 %
• Gram negatives are sensitive to meropenem and amikacin but highly resistant to
cephalosporins
• Mortality rate of febrile neutropenia was 21.8%.
.
1-Apr-23 Febrile neutropenia 14
Kiros T. Treatment outcome and factors of febrile neutropenia among pediatric
patients with cancer in ACSH, sep,2020

15. Etiology of fever …
• Fungi
• Typically Candida spp, are more likely to be recovered after prolonged
courses of broad-spectrum antibiotics but occasionally may be the primary
pathogen
• Aspergillus spp, Zygomycetes, and Cryptococcus spp
• Antifungal prophylaxis shift the distribution from Candida spp and toward
mold infections.
• Viral etiologies
• Most significant are HSV and VZV
• Respiratory viruses are also frequently detected in nasopharyngeal aspirates
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16. Clinical manifestations FN
• Fever often is the sole sign of occult infection in the neutropenic host
• This sign may be absent in some infected patients may present with
hypothermic, hypotensive, listless, or confused
• Infected children who are receiving glucocorticoids
• May present with a lower and/or intermittent temperature elevation or may
be afebrile
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17. Clinical manifestations FN
 Signs and symptoms of inflammation are often attenuated or absent in
neutropenic patients
• Bacterial infections of skin and soft-tissue
• Lack induration, erythema, warmth, or pustulation
• Pulmonary infection
• No discernible infiltrateon a radiograph
• Meningitis
• CSF pleocytosis might be modest or absent
• Urinary tract infection may demonstrate little or no pyuria
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18. Patient approach
• Detailed HX and P/E with special attention to clues
• Suggesting etiology or focus of infection
• Try to identify any features that may help to risk stratify the patient
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19. Patient approach …
• Detail History
• Important aspects of HX include :
• New site-specific symptoms
• Antimicrobial prophylaxis
• Infection exposures
• History of documented infections or colonization
• Concomitant noninfectious cause of fever (eg, receipt of blood products)
• Underlying co morbid conditions (eg, diabetes, recent surgery)
• Previous chemotherapy, agents used, and the stage of therapy (to anticipate
the length of the Neutropenic episode)
• Intravascular catheters or other devices
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20. Patient approach …
• Physical examination
• A careful P/E particular attention paid to most commonly infected sites :
• Abnormal vital signs, particularly tachycardia (even without hypotension)
• HEENT
• Sinus tenderness or nasal ulcerative lesions
• Oral mucosa and periodontium
• Pharynx
• Lower esophagus
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21. Patient approach …
• Lungs
• Tachypnea & saturation
• Abdomen
• Retrosternal burning pain
• Decreased bowel sounds
• Typhilitis/colitis
• Acute abdomen (RLQ pain)
• Hypotension
• Bloody diarrhea
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22. Patient approach …
• Perineum, particularly the perianal and labial regions
• Perirectal abscess
• Erythema
• Induration
• Anorectal pain, tenderness and painful bowel movements.
• In the neutropenic patient, pus will be absent and the patient will present with
a brawny edema and dense cellulitis.
1-Apr-23 Febrile neutropenia 22

23. Patient approach …
• Skin
• Skin folds
• Areas surrounding nail beds,
• Central venous line exit sites and subcutaneous tunnel
• Sites of bone marrow aspiration and lumbar puncture
• Mild Erythema or tenderness should not be ignored
• Visual signs of inflammation may become evident only when neutrophil
counts are recovering.
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24. Investigations of FN
• CBC
• Liver and renal function
• Obtain peripheral blood cultures
• Consider urinalysis and urine culture in patients where clean catch midstream
specimen is readily available.
• Obtain chest X-ray only in symptomatic patients
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25. Investigations of FN…
• Blood culture
• Obtaining a blood culture of an adequate volume from all lumens of the CVC
is important.
• Utility of peripheral blood cultures in addition to CVC cultures is
controversial.
• Seven studies evaluated concurrent peripheral and CVC cultures in adults and
children with cancer and/or undergoing HSCT
• The proportion of Bacteremia detected by peripheral blood cultures alone
(CVC cultures were negative) was 13% (95% CI 8-18%).
1-Apr-23 Febrile neutropenia 25
IDSA 2010

26. Investigations of FN…
• Variables influence blood culture yield
• Blood culture volume
• Choice of media type
• Number of culture bottles inoculated
• 2 retrospective studies found that
• 2 blood culture sets detect 80%–90% of bloodstream pathogens
• whereas >3 sets are required to achieve >96% detection
• Accordingly, at least 2 sets of blood culture specimens should be obtained
1-Apr-23 Febrile neutropenia 26
CPG guideline for use of antimicrobial agent in neutropenic
cancer patients , 2010

27. Investigations of FN…
Urinalysis and Urine Culture
• Pyuria was found in only 4% of UTI
• Nitrite testing in younger children to be less effective
• Urine culture if symptoms or abnormal urinalysis present
• Avoid invasive methods
• Clean-catch or midstream urine collection is recommended.
• Urine should be obtained prior to commencing antibiotics
• Urine collection should not delay treatment.
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28. Investigations of FN…
• CXR:
• Routine CXRs are not recommended in asymptomatic children
• Had been advocated as part of the routine, initial assessment of pediatric FN
• Four studies that included 540 episodes of FN examined the value of routine CXR
• Frequency of pneumonia in an asymptomatic child was 5% or less each of
them
• Asymptomatic children who do not receive a CXR had no significant adverse
clinical consequences
• Findings
• New focal lesion in patient recovering from neutropenia
• New focal lesion in patient with continuing neutropenia
• New interstitial pneumonitis
• induced sputum or Bronchoalveolar lavage
1-Apr-23 Febrile neutropenia 28
Guideline for mgt of PNF ,IDSA 2010

29. Investigations of FN…
• Fungal
• Serial serum tests for fungal antigens or DNA
• D glucan test sensitivity (63%–90%) and specificity (>95%)
• Candida species
• Aspergillus species
• Pneumocystis species
• Fusarium species
• Galactomannan test ( 58-65 vs 65-95%)
• Aspergillus species
• BAL fungal culture
• PCR of blood and BAL fluid
• High-resolution chest CT
• Macronodules with or without a halo sign  Aspergillosis
• Halo sign represents edema or blood surrounding the nodule
• nodular, wedge-shaped, peripheral, multiple, or cavitary lesions.
1-Apr-23 Febrile neutropenia 29

30. Risk stratification
• Risk stratification at the time of a child’s presentation with FN
• May allow for intensification of therapy
• Monitoring for those at higher risk for serious infections and/or
complications
• De-escalation of therapy for those at lower risk for severe FN outcomes.
• Patients with fever and neutropenia can be divided into high- and low-risk categories
based upon
• Presenting signs and symptoms
• ANC
• Underlying cancer
• Type of therapy and the anticipated length of neutropenia
• Medical comorbidities.
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31. Risk stratification…
• Use of a risk stratification strategy is important, and individual institutional
standards of care for risk assignment should be based on one of the six validated
schemas.
• Each institution should maintain records of which specific strategy was used and
evaluate the performance of the chosen rule to ensure accuracy and safety within
the specific clinical setting
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32. Risk stratification…
1-Apr-23 Febrile neutropenia 32
ICON 2016 , guideline for mgt of FN

33. Risk stratification…
High-risk
• Patients with FN with the following criteria , but not limited to:
• Hemodynamic instability
• Oral or GI mucositis that interferes with swallowing or causes diarrhea
• GI symptoms (abdominal pain, nausea, vomiting, or diarrhea)
• New-onset neurologic or mental status changes
• Intravascular catheter infection
• New pulmonary infiltrate or hypoxemia or underlying chronic lung disease
• Hepatic/renal insufficiency
• Patients with ALL, AML, or within 30 days of HCT
• NB
• High-risk patients should be admitted to the hospital for empiric antimicrobial
therapy.
1-Apr-23 Febrile neutropenia 33

34. Risk stratification…
• Low-risk FN
Low-risk patients are those with :
• Neutropenia expected to resolve within seven days
• Stable and adequate hepatic and renal function
• No active comorbidities
• Nontoxic appearance
• No identifiable source of fever
• Normal chest radiograph
• Malignancy in remission status.
1-Apr-23 Febrile neutropenia 34

35. Management of FN
• Factors to be considered in Initial management of pediatric FN
• Patient characteristics
• Clinical presentation
• Local infrastructure to support different models of care
• Drug availability and costs
• Local epidemiology of resistance patterns
1-Apr-23 Febrile neutropenia 35

36. Management of FN…
• Goal of empiric therapy
• To provide coverage for virulent organisms and prevent serious morbidity and
mortality
• Minimizing exposure to unnecessary antibiotics and prevent antibiotic
resistance rates
1-Apr-23 Febrile neutropenia 36

37. Cont…
• The cornerstone of therapy for the febrile, neutropenic patient is prompt initiation
of empiric broad-spectrum antibiotics with antipseudomonal activity to reduced
the mortality rate for Gram-negative infections significantly.
• Administration of antibiotic therapy more than 60 minutes after presentation has
been associated with increased adverse outcomes and length of stay .
• In an observational study in pediatric cancer patients, receipt of antibiotics within 60
minutes of presentation was associated with decreased rates of ICU consultation or
admission among.
1-Apr-23 Febrile neutropenia 37

38. Empirical Treatment options
• Monotherapy
• Ticarcillin/clavulanate
• Piperacillin/tazobactam
• cefepime
• Imipenem or meropenem
• Two-drug regimen:
• cefepime, or ceftazidime AND gentamicin (or tobramycin or amikacin).
• Ticarcillin/clavulanate or Piperacillin/tazobactam and gentamicin (or tobramycin
or amikacin).
• NB
• Imipenem or meropenem should not be prescribed routinely as empiric therapy.
1-Apr-23 Febrile neutropenia 38

39. Cont…
• Recommendations on empirical antibiotics use in pediatric HR FN
• Monotherapy with an anti-pseudomonal ß-lactam or a carbapenem
( strong recommendation, high-quality evidence)
• Result from 2 meta-analyses compared monotherapy versus an aminoglycoside-
containing regimen in FN and in immunocompromised patients with sepsis in
adults
• Non-inferiority of monotherapy regimens
• Higher toxicity with combination regimens
1-Apr-23 Febrile neutropenia 39
Guideline for mgt of PNF, IDSA 2010

40. Cont…
• In review of 68 randomized trials, which includes 30 more trials than the 38
randomized trials.
• Found that monotherapy is similar in efficacy and safety in comparison with
aminoglycoside-containing combination regimens
• Reduce costs , toxicity, and the need for therapeutic drug monitoring
• Fourth-generation cephalosporin monotherapy is an appropriate option for
empirical pediatric high-risk FN management if institutional factors support its
use.
1-Apr-23 Febrile neutropenia 40
Paula D. robinson etal , Strategies for Empiric Management of Pediatric FN in Patients With
Cancer and HSCT Recipients,, journal of clinical oncology ,2016

41. Cont…
• A pediatric meta-analysis found included only 4 trials with patients younger than
14 years of age show
• Fewer treatment failures with monotherapy (OR 0.88, 95% CI 0.78-0.99)
• Aminoglycoside-containing combination treatment did not improve clinical
outcomes in comparison to monotherapy.
• Limitation – limited trials
1-Apr-23 Febrile neutropenia 41
Guideline for mgt of PNF, IDSA 2010

42. Cont…
1-Apr-23 Febrile neutropenia 42
ICON 2016 , guideline for mgt of FN

43. Modification of treatment: after 24-72 hr empirical RX
If responding to empiric therapy
• Do not modify based solely on
persistence of fever if clinically
stable
• Discontinue double gram-negative,
or empiric glycopeptides coverage
(if initiated) after 24-72 hours
UNLESS combination is justified
by specific microbiologic
indication
If NOT responding to empiric therapy
• If persistent fever and clinically
unstable
• Escalate initial empiric antibacterial
regimen to include coverage for
• Resistant gram negative
• Gram-positive
• Anaerobic bacteria
1-Apr-23 43
Febrile neutropenia

44. Cont…
• MRSA: addition of Vancomycin, linezolid, or daptomycin
• VRE: Consider early addition of linezolid or daptomycin
• ESBLs: Consider early use of a carbapenem
• penicillin-allergic patients can be treated with ciprofloxacin plus clindamycin
or aztreonam plus vancomycin
1-Apr-23 Febrile neutropenia 44

45. Treatment Cessation :After 24-72 hr empirical RX
For all patients
• Discontinue empiric antibiotics
if:
• blood culture negative at 48 hrs
• Afebrile for at least 24 hours, and
• There is evidence of bone marrow
recovery
For low-risk FN
• Consider discontinuation of empiric
antibiotics in low-risk patients at 72
hours irrespective of marrow recovery
status, if:
• Blood culture negative,
• Afebrile for at least 24 hours, as
long as careful follow-up is ensured
1-Apr-23 45
Febrile neutropenia

46. Treatment Cessation :After 24-72 hr empirical RX
For all patients
• Discontinue empiric antibiotics
if:
• blood culture negative at 48 hrs
• Afebrile for at least 24 hours, and
• There is evidence of bone marrow
recovery
For low-risk FN
• Consider discontinuation of empiric
antibiotics in low-risk patients at 72
hours irrespective of marrow recovery
status, if:
• Blood culture negative,
• Afebrile for at least 24 hours, as
long as careful follow-up is ensured
1-Apr-23 46
Febrile neutropenia

47. Cont…
1-Apr-23 Febrile neutropenia 47
ICON 2016 , guideline for mgt of FN

48. Indication for vancomycin consideration
• Suspected central venous catheter-related infection
• Patients with AML because of the increased risk of infection with alpha hemolytic
streptococcus such as Streptococcus mitis
• Prior history of alpha hemolytic streptococcus Bacteremia
• Patients colonized with resistant organisms only treatable with vancomycin
• Recent history of Bacteremia or venous catheter-related infection requiring
vancomycin
• Intensive chemotherapy causing mucositis (such as high-dose cytosine
arabinoside)
• Hypotension
• Patients who have developed fever despite quinolone prophylaxis.
1-Apr-23 Febrile neutropenia 48

49. Management of fungal infection
• The risk of fungal infections is related to the cytotoxicity of the chemotherapeutic
regimen and the duration of neutropenia.
• The major cause IFIs
• Aspergillus and Candida with a mortality approaching 30–60% with.
• Higher among post-hematopoietic stem cell transplantation patients.
• Prompt diagnosis and treatment is paramount to improving outcomes in these
patients.
• Difficulty in diagnosing fungal infections is caused by
• Absence of localizing signs and symptoms
• High likelihood of negative blood cultures.
1-Apr-23 Febrile neutropenia 49

50. Risk stratification of IFIs
• High risks invasive fungal infection
• Acute myeloid leukemia
• Relapsed acute leukemia
• Highly myelosuppressive chemotherapy
• Allogeneic hematopoietic cell transplant recipients
• Children with prolonged neutropenia
• Children receiving high-dose corticosteroid
• Low-risk of IFIs - if do not fulfill the above three criteria
1-Apr-23 Febrile neutropenia 50

51. Empiric Treatment IFD
High risk IFIs
• Start empiric antifungal therapy if
persistent or recurrent fever of unclear
etiology at or beyond 96 hours of
broad-spectrum antibacterial
treatment.
Low risk IFIs
• consider empiric antifungal therapy if
persistent or recurrent fever of unclear
etiology at or beyond 96 hours of
broad-spectrum antibacterial treatment.
1-Apr-23 51
Febrile neutropenia

52. Management …
• Choice of antifungal:
• Caspofungin, or liposomal Amphotericin B
• Amphotericin-B in places with limited resources
• Prophylactic antifungal therapy in children with IFD high risk
• No studies evaluating the safety of this approach in pediatric patients found
• Research needed to evaluate its safety and effectiveness in children.
1-Apr-23 Febrile neutropenia 52

53. Management …
• Cessation of antifungal therapy:
• No data exists to guide this decision
• International pediatric FN guideline panel agrees that empiric therapy should
be continued until absolute neutrophil count rises to100-500/µL, and no
documented or suspected IFD.
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54. Management …
• Antiviral therapy
• Antiviral treatment for HSV or VZV is only indicated if there is clinical or
laboratory evidence of active viral disease .
• Respiratory virus testing ( influenza, parainfluenza, adenovirus) and CXR are
indicated for patients with URT symptoms ( coryza, cough).
1-Apr-23 Febrile neutropenia 54

55. Typhilitis/Neutropenic Enterocolitis
• Necrotizing colitis localized in the cecum, occurs in the setting of severe
neutropenia, particularly in patients with leukemia and in stem cell transplant
recipients.
• Should be strongly suspected in patients with right lower quadrant pain or the
development of a partially obstructive right lower quadrant mass.
• Result of bacterial or fungal invasion of the mucosa and can quickly progress
from inflammation to full-thickness infarction to perforation, peritonitis
and septic shock.
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56. Typhilitis …
• Responsible pathogens include
• Pseudomonas species, Escherichia coli, other Gram negative bacteria
• Staphylococcus aureus, a-hemolytic Streptococcus, Clostridium,
• Aspergillus, and Candida.
• Typhilitis in patients receiving chemotherapy is linked to mucosal injury caused
by cytotoxicity chemotherapeutic agents.
• The cecum is usually affected ...> its distensibility and its diminished
vascularization relative to the rest of the colon.
• Extends into the ascending colon and terminal ileum
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57. Clinical manifestations of typhilitis
• Neutropenic enterocolitis must be considered in any severely neutropenic
patient (ANC <500 cells/microL) who presents with fever and abdominal
pain.
• The location of abdominal pain right lower quadrant.
• fever, frequently appear during the 3rd week (median 17 days) after
receiving cytotoxicity chemotherapy
• At a time when neutropenia is most profound.
• Abdominal distension, cramping, tenderness, nausea, vomiting, watery or
bloody diarrhea, and frank hematochezia.
• Paralytic ileus may occur but is uncommon.
• Peritoneal signs and shock suggest the possibility of bowel wall
perforation.
• Stomatitis and pharyngitis, suggesting the presence of widespread
mucositis, may be present.
1-Apr-23 Febrile neutropenia 57

58. Cont…
• Diagnosis
• Typhilitis is usually diagnosed clinically when a neutropenic patient presents
with right lower quadrant pain.
• Physical examination may reveal an
• Absence of bowel sounds
• Bowel distention
• Tenderness on palpation maximal in right lower quadrant
• A palpable mass in right lower quadrant.
• Serial abdominal examinations are required
• Blood and stool cultures and C. difficile toxin assays
1-Apr-23 Febrile neutropenia 58

59. Cont…
• Imaging studies may aid in the diagnosis of typhlitis:
• Radiograph of the abdomen
• Reveal pneumatosis intestinalis
• free air in the peritoneum
• Wall thickening
• US
• Thickening of the bowel wall in the region of the
• cecum and is becoming a
• More commonly used non-radiation modality to image for typhlitis
• CT scan
• definitive imaging study and may
• demonstrate diffuse thickening of the cecal wall
• Barium enema
• show severe mucosal irregularity, rigidity, loss of haustral markings and
occasional fistula formation
1-Apr-23 Febrile neutropenia 59

60. Cont…
• Medical management is the initial treatment:
• Discontinuation of oral intake
• Nasogastric tube suctioning
• Broad-spectrum antibiotics (anaerobic , Gram-negative and anaerobic)
• Piperacillin-tazobactam /Cefepime/Meropenem with/out metrodazole
• Vancomycin with indication
• Intravenous fluid and electrolytes
• Packed red cell and platelet transfusions, as indicated
• Vasopressors, as needed (hypotension is associated with a poor outcome).
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61. Cont…
• Indications for surgical intervention:
• Persistent GI bleeding despite resolution of neutropenia and thrombocytopenia
• Evidence of free air in the abdomen on abdominal radiograph
• Uncontrolled sepsis from bowel infarction requiring fluid and pressor support
• Mortality is related to bowel perforation, bowel necrosis and sepsis.
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62. Cont…
• Fungemia and fungal invasion of the bowel can occur
• Candida spp are the most common cause of fungal bloodstream infection in
patients with neutropenic colitis.
• Protracted fever (>72 hours) despite broad-spectrum antibiotics.
• Voriconazole and amphotericin B formulations.
1-Apr-23 Febrile neutropenia 62

63. Management …
• Myeloid CSFs
• Are not recommended as adjuncts to antibiotics
• Minimally (but statistically significantly) decreased
• Days of neutropenia
• Duration of fever
• Length of hospital stay
• The actual clinical benefit of these reductions is not convincing.
• None of the studies demonstrated a survival benefit associated with
therapeutic CSFs.
• Given the cost of and adverse effects and lack of consistent clinical data
associated with the CSFs routine use is not advocated
1-Apr-23 Febrile neutropenia 63
Guideline FN IDSA 2010

64. Management …
• Prevention of febrile neutropenia
• Hand hygiene
• Standard barrier precautions and infection specific isolations.
• HSCT recipients should place in private room
• Allogeneic HSCT recipients should placed in private room with >12air exchange
/hr and high efficacy particulate filter room
• Plants and dried or fresh flowers should not allowed in the room of hospitalized
neutropenic patients
• Hospital work exclusion policies should be designed to encourage health workers
to report their illness or exposure.
1-Apr-23 Febrile neutropenia 64

65. Summery
• Fever is frequently the only clinical manifestation of serious infection in a
neutropenic cancer patient,
• Infection is the major cause of treatment related mortality for children with cancer
• Prompt initiation of empiric, broad-spectrum, intravenous antibiotic therapy is the
single most important life-saving intervention in these patients and should Treated
as an emergency.
• Vital sign Q1hr until stable then Q4hror as indicated
• Acetaminophen is the preferred antipyretic agent.
1-Apr-23 Febrile neutropenia 65

66. Guidelines for the management of febrile neutropenia in ACSH,
2021
ACSH Hemato-oncology unit
1-Apr-23 Febrile neutropenia 66

67. Definition
• The neutropenic patient
• ANC < 500 x 109 /L or ≤1 x 109 /L with predicted fall to < 0.5 x 109 /L)
must be admitted and given intravenous antibiotics in the event of a single
temperature spike of >37.8°C axillary or a temperature of ≥37.5°C axillary
taken on two occasions at least one hour apart
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68. Cont…
Please do
• CBC and Differential immediately
• Liver and renal function
• Obtain 2 blood culture sets from separate peripheral vein puncture
• IV antibiotics should be started within 1 hour
• Provide blood transfusion if indicated
• Consult pediatric hemato-oncologist
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69. Risk stratification
Low risk features
• Vitally stable
• No evident focus of infection
• ANC>100 and anticipated to rise
within 7days
• Solid tumors and ALL during
maintenance
• No abdominal pain
High risk features
• AML, MDS, ALL(during induction,
consolidation , re-induction), NHL
• ANC<100, and/or anticipated to extend >
7 days
• Presence of any co-morbid medical
problem including: vital instability, GIT
manifestation, pneumonia, altered mental
status
• Vital instability: Hypotension, tachypnea,
Hypoxia (O2 sats < 94% in room air)
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70. Management of FN
Low risk features
• Start with ceftriaxone and
gentamicin
• 2nd line: Ceftazidime &Vancomycin
• Outpatient management
• who refused inpatient management
• Do blood culture
• first dose of ceftriaxone and
gentamicin IV at PEOPD
• Ciprofloxacin and Augmentin PO
• Phone number
High risk features
• Start ceftazidime and gentamicin
• 2ndline: cefepime
• Ciprofloxacin if microbiological
documented
• Vancomycin can be used as first line
based on indications
• Metronidazole for abdominal
symptoms or suspected C. difficile
infection
•
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71. Treatment Cessation :after 24-72 hr empirical RX
For all patients
• Discontinue empiric antibiotics
if:
• blood culture negative at 48 hrs
• Afebrile for at least 24 hours, and
• There is evidence of bone marrow
recovery
For low-risk FN
• Consider discontinuation of empiric
antibiotics in low-risk patients at 72
hours irrespective of marrow recovery
status, if:
• Blood culture negative,
• Afebrile for at least 24 hours, as
long as careful follow-up is ensured
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72. Treatment Cessation :after 24-72 hr empirical RX
For all patients
• Discontinue empiric antibiotics
if:
• blood culture negative at 48 hrs
• Afebrile for at least 24 hours, and
• There is evidence of bone marrow
recovery
For low-risk FN
• Consider discontinuation of empiric
antibiotics in low-risk patients at 72
hours irrespective of marrow recovery
status, if:
• Blood culture negative,
• Afebrile for at least 24 hours, as
long as careful follow-up is ensured
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73. Empiric Treatment IFD
High risk IFIs
• start empiric antifungal therapy if
persistent or recurrent fever of unclear
etiology at or beyond 96 hours of
broad-spectrum antibacterial
treatment.
• Liposomal Amphotericin B
Low risk IFIs
• consider empiric antifungal therapy if
persistent or recurrent fever of unclear
etiology at or beyond 96 hours of broad-
spectrum antibacterial treatment.
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74. Reference
• Up to date 2018
• Clinical practice Guidelines for the use of antimicrobial Agents in neutropenic
patients with cancer :2010 update by Infectious Disease Society of America
• Manual of Pediatric Hematology &Oncology,5th edition
• Guideline for the management of fever and neutroprnia in children with cancer
and HSCT recepient ,2017
• Nelson text book of pediatrics ,21st edition
• Febrile neutropenia current guidelines for children, ICON 2016
• CPG guideline for use of antimicrobial agent in neutropenic cancer patients ,
2010
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75. Thank you!
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