Answering Specific Questions in the management of febrile neutropenia

1. Febrile Neutropenia
Ahmed Rashwan
Medical Oncology Registrar
KCCC
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4. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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5. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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6. The Add-On Strategy
• A beta-lactam is started in the first fever.
• Vancomycin is added after a few days of persistent fever.
• The beta-lactam is changed after a few days if the patient is still febrile.
• And finally, empiric antifungal therapy if started in case of persistent fever.
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7. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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8. Should I Give Antibacterial Prophylaxis?
• Quinolone (ciprofloxacin or levofloxacin).
• Associated with a reduction in fever and bacterial infection frequency and
a modest impact on mortality
• The literature review failed to show an increase in resistance with the use
of quinolones, including two randomized trials and one meta-analysis
• Quinolones' side effects such as mental disturbances, fatal
hypoglycemia, aortic dissection and rupture of aortic aneurysm, disabling
side effects on tendons muscles, joints and nerves,
• Unless there is an additional risk for potentially severe side effects, I give
ciprofloxacin 500 mg BID (or levofloxacin 500 mg/d)
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9. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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10. Should I Give Antifungal Prophylaxis?
• Fluconazole as a prophylaxis by metanalysis increased survival and
decreased incidence of invasive candidiasis in patient with prolonged
neutropenia, BUT Invasive aspergillosis and other filamentous fungi
became more frequent.
• Prophylaxis by Posaconazole & Caspofungin decreased incidence and
mortality by IFD and Aspergellosis, But Voriconazole & Micafungin did not.
• Choice of Prophylaxis depend on Age, Comorbidities, Environmental
exposure, WBC.
• Azole strongly inhibit CYP3A4 enzymes
• Vincristine toxicity increased with Azoles and can be life threatening.
• Echinocandins better if high liver enzymes or Severe GI mucositis.
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11. • If prophylaxis by Fluconazole:
1. active monitoring with serial (2-3x/week) serum
galactomannan.
2. The Options: Echinocandin (Anidulafungin, Caspofungin,
Micafungin), Voriconazole, and Liposomal amphotericin B
• If Prophylaxis by Posaconazole :
1. Serum galactomannan upon clinical suspicion for 3
consecutive days.
2. The Options: Liposomal Amphotricin B
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12. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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13. What is the Workup in the First Fever?
• Any S/S must be seriously taken into account.
• presents signs of infection (e.g., abdominal pain in the context
of gastrointestinal mucositis or cellulitis) without fever.
• Workup:
1. History
2. Physical Examination.
3. Investigations
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14. ❖ History:
1. Detailed medical history: co-morbidities and prior infections (e.g.,
chronic lung disease, sinusitis, diabetes, smoking habit, herpes
virus infection, varicella, tuberculosis).
2. Prior episodes of febrile neutropenia with information about the
documentation of infection and colonization by resistant organisms,
concomitant medications, and symptoms of infection.
❖ Physical Examination:
- Particular attention to the skin, nails, and respiratory and digestive
tracts.
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15. ❖ Investigations:
• At least two sets of blood cultures (aerobic, anaerobic, and
fungal bottles), one from a peripheral vein and another from a
catheter.
• Routine Chest X ray is NOT indicated.
• If Clinically Indicated
1. Computed tomography (CT) scans.
2. PCR panel for respiratory viruses.
3. PCR panel for diarrhea in patients with such symptoms.
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16. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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17. What is the Empiric Antibiotic Regimen for the First Fever?
• In febrile neutropenia, the event of early death is common with G-ve bacteremia.
• Since the late 1990s, monotherapy with a beta-lactam is preferred.
• Empiric Vancomycin is NOT recommended routinely unless there is suspected catheter-
related infection, skin and soft tissue infection, pneumonia, or hemodynamic instability.
• For patients without colonization by MDR Gram-negative bacteria, Give cefepime in
extended infusion (3-4 hours), with the dose and schedule adjusted for the creatinine
clearance.
• For patient with signs of typhlitis, Add metronidazole to cefepime.
• If suspected MDR G-ve bacteria (e.g. another patient in same unit infected with MDR,
or Infection MDR in previous FN episode),
1. Order active screening with weekly (or on admission) rectal swabs.
2. Start an empiric antibiotic regimen active against the colonizing MDR Gram-negative bacteria.
3. if the patient is stable and blood cultures are negative on Day 3 de-escalation strategy is applied.
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18. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile
Neutropenia?
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19. When Should I Change the Empiric Antibiotic Regimen?
❖ Persistent fever after the start of Empiric Antibiotic is frequent
• Check if hemodynamically stable.
• Check Clinical and microbiological data.
• The median time to defervescence :
a) 3 days in episodes without documented infection.
b) 4 days in those with clinical or microbiological documentation.
c) 4 days in Gram-negative bacteremia.
d) 5 days in Gram-positive bacteremia.
• Careful review of symptoms and physical examination.
• Obtain Additional blood cultures.
• Repeat biomarkers e.g. CRP, Serum Galactomannan.
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20. • Check if there is any new signs and symptoms:
a) Anal pain, abdominal pain, Add Metronidazole.
b) Clinical deterioration, Switch β-lactam.
c) Skin infection colonized by MRSA, Add Vancomycin.
d) Documented infection by VRE, Add Linezolid or Daptomycin.
• If suspected Fungal infection,
1. Serum Galactomannan + CT Sinuses & Chest, and start preemptive antifungal
2. If CT Chest is suspicious, S. Galactomannan –ve -> Do bronchoalveolar lavage
• If suspected typhilitis, Do CT Abdomen
• If Diarrhea, Do stool test for C.Difficile.
• If New skin nodular lesion, Do skin biopsy
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21. • So, the strategy of empiric change in the antibiotic regimen
after 3-4 days of a patient with persistent fever and no new
signs of infection is inappropriate and will likely result in the
overuse of antibiotics without improving the outcome.
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22. 1. The Add-On Strategy
2. Should I Give Antibacterial Prophylaxis?
3. Should I Give Antifungal Prophylaxis?
4. What is the Workup in the First Fever?
5. What is the Empiric Antibiotic Regimen for the First Fever?
6. When Should I Change the Empiric Antibiotic Regimen?
7. When Should I Discontinue Antibiotics in Febrile Neutropenia?
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23. When Should I Discontinue Antibiotics in Febrile Neutropenia?
• Documentation of infection and Neutrophil recovery.
• If there is Documented Infection, the usual recommendation
is to define the duration of treatment based on the infection that
was diagnosed, keeping the antibiotic regimen at least until
neutrophil recovery.
• If there is No Documented Infection, the recommendation
had been to keep the empiric regimen until neutrophil recovery,
provided that vital signs are normal and the patient has no
oral or gastrointestinal mucositis.
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