Workup for Fever in a Patient with Neutropenia David Thom, MD, PhD Associate Professor Family

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Work-up for Fever in a Patient with Neutropenia
David Thom, MD, PhDAssociate ProfessorFamily
Community Medicine
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Overview

• Definitions
• Principles of Diagnosis
• Choice of diagnostic studies
• Treatment

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Definition of Fever

• Temp gt 38.3o C once or
• Temp gt 38o C twice in 12 hours

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Definition of Neutropenia

• WBC multiplied by (neutrophils bands)
• lt 1000/mm3 mild
• lt 500/mm3 usual definition
• lt 200/mm3
• lt 100/mm3 severe

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Does the Cause of Neutropenia Matter?

• Different distribution of other risk factors,
  including age
• Differences in co-morbid conditions
• Not clear on to what degree studies in one
  group can be generalized to the other but
  thats what we do

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Implications of Neutropenia

• Increased risk of infection
• Less likely to have localizing signs and
  symptoms
• Both of above more common with more severe
  neutropenia
• Prompt initiation of antimicrobial therapy is
  important

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Localizing signs and symptoms

• Among neutropenic patients ultimately diagnosed
  with pneumonia, about half with a neutrophil
  count lt 1000 had a normal chest x-ray on
  presentation.
• Of those with neutrophil count lt 100, only 8
  had purulent sputum

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Diagnosis - principles

• Most important diagnostic tool is the PE
• Lack of PMNs, inflammation, common
• Because signs and symptoms may be slow to
  develop, frequent re- assessment and re-testing
  is commonly indicated
• Multiple organisms, secondary infections are
  common

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Diagnosis

• Recommended tests
• Laboratory studies
• Chest X-ray (may need to repeat)
• Blood cultures (including line cultures)
• Sputum culture
• Urine culture

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Diagnosis

• Other tests to consider
• CT/MRI of head, chest or abdomen
• High resolution chest CT detected pneumonia in
  gt50 neutropenic pts. with fever gt48 hrs and
  normal CXR1
• Stool for culture, C. difficile, O P
• Biopsy of skin or other suspicious area
• Bronchoalveolar lavage

1. Heussel J Clin Oncol 199917796.
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Diagnosis

• No tests or set of tests have been shown to
  change clinical outcomes
• No agreed upon method of risk stratification
  for diagnostic testing
• In general, sicker patients and patients who
  have not responded to empiric therapy need more
  aggressive diagnostic testing

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Infectious Agents

• Only about 30 of neutropenic patients with
  fever have an infectious source initially
  identified1,2
• Estimated that 80 of identified infections are
  from endogenous flora

1. Pizzo, PA. NEJM 19933281323 2. Link et
al. Ann Hematol 200382 (suppl 2)S105-7
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Infectious Agents

• Common gram negative organisms1
• E. coli
• Klebsiella sp.
• Pseudomonas sp.
• Enterobacter sp.

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
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Infectious Agents

• Common gram positive organisms1
• Coag negative Staphylococcus
• S. aureas
• S. pneumoniae
• Corynebacterium
• Other streptococci sp.

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
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Infectious Agents

• Other common organisms1
• C. difficile
• Anerobes
• Aspergillus
• Candida sp.
• Mycobacteria sp.

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
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Empiric antibiotic regimens

• Low risk defined as neutropenia lt 6 days and no
  major medical compli- cations and neutrophil
  count gt 200
• High risk is neutropenia for 10 days or longer
  or major medical complication or neutrophil
  count lt100

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
17
Empiric antibiotic regimens

• Single agent (low or intermediate risk
  patients)
• cefipime, ceftazidime, imipenem, meropenem
• Dual agent (higher risk)
• beta-lactam (e.g. piperacillin)
  amincoglycoside (e.g., gentamycin) or
  ciprofloxin

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
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Empiric antibiotic regimens

• Additional therapy (high risk or not
  responding)
• Vancomycin
• Amphotericin (also variconazle, caspofungin,
  intraconazole)

1. Link et al. Ann Hematol 200382 (suppl
2)S105-7
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Principles of Empiric Therapy

• Coverage for common gram negative and gram
  positive organisms
• Add coverage for fungal infection at between 3
  to 7 days if patient not responding
• Initial coverage for anerobes if infection of
  sinuses/gums or anus/rectum or if suspect
  intra-abdominal or pelvic infection

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Choice of Empiric Therapy

• Continue abx treatment at least 7 days after
  defervescence1
• For staph aureus, continue for 2 weeks from
  last positive blood culture1
• Outpatient treatment has been studied, but only
  recommended in selected cases of low risk and
  high compliance

1. Buchheidt et al Ann Hematol 200382 (suppl
2)S127-32
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Summary

• Lack of typical signs and symptoms
• Basic work up as for non-neutropenic patients
• Additional studies as indicated
• High rate of false negatives
• Keep searching!
• May be multiple organisms
• Most therapy is empiric

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References
Brodey GP, Rolston KVI. Management of fever in
neutropenic patients. J Infect Chemother
200171-9 Buchheidt D, Bohme A, Cornely OA, et
al. Diagnosis and treatment of documented
infections in neutropenic patients Ann Hematol
200382 (suppl 2)S127-32 Huessel CP, Kauczor HU,
Huessel GE, et al. Pneumonia in febrile
neutropenic patients and in bone marrow and blood
stem-cell transplant recipients use of
high-resolution computed tomography. J Clin
Oncol 199917796-805 Link H, Bohme A, Cornely
OA, et al. Antimicrobial therapy of unexplained
fever in neutropenic patients Ann Hematol 200382
(suppl 2)S105-17 Pizzo PA. Management of fever
in patients with cancer and treatment-induced
neutropenia. New Engl J Med 1993