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Neutropenic Fever

November 10, 2019

This is Doctor Kathleen Kiernan, I’ll be presenting neutropenic fever. I’m a Duke University Medical Center second-year resident. The learning objectives for this presentation are as follows. Basically you’ll need to know the definition of neutropenic fever, know how to assess the patient who has this problem, and know what concepts you’ll need to use in terms of therapy in this setting. The outline for this presentation includes the definition of both neutropenia and neutropenic fever, how to assess this particular patient, which laboratory studies and microbiologic data you should obtain, what concepts you should know surrounding therapy and the choice of antimicrobials, a case for review, and finally at the end a practice board question. The definition of neutropenic fever begins with the definition of neutropenia. This is defined as an absolute neutrophil count or an ANC of less than 500. I’ve included in front of you the calculation for how to do this, although in general you will not need to know this. Neutropenic fever is a single temperature of greater than or equal to 38.3 degrees Celsius, which is 101 degrees Fahrenheit, or a sustained temperature of 38.0 degrees Celsius for more than one hour in a patient with neutropenia. Just a little bit about neutrophils, their form and their function. They are called neutrophils because they in a neutral pink on an H&E stain, unlike eocynaphils, which stain a bright red, or basophils, which stain a deep blue. They’re larger than red blood cells, as you can see, and they have a segmented nucleus with bridging chromatin, which are the strings you can see between the parts of the nucleus in front of you. The initial assessment of this patient would include an updated focused history, any new signs or symptoms that have developed, followed by a thorough physical exam. Looking over the skin, a good pulmonary exam, a neurologic exam, and also asking any questions related to a abdominal complaints while examining the abdomen. The laboratory studies would be a CDC with differential, a BUN and Creatanine or chem 7, as well as transaminases or a GI panel. Microbiologic data is some of the most important data you obtain, including blood and urine cultures, a chest x-ray. a Clostridium difficile toxin, especially if they’re having symptoms such as more than three watery bowel movements in a day. The most important thing to see about this busy slide for treatment of a patient with neutropenic fever are the patients are divided into two main categories– low risk and high risk. Low risk patients are those with anticipated neutropenia for less than a week who are clinically stable and generally are pretty healthy, with no other major medical problems. High risk patients are those who are anticipated to be neutropenic for more than seven days, who clinically unstable. Generally anyone who is an in-patient and anyone with medical comorbidities. The second most important thing to see about this slide is involving inpatient IV antibiotics. The choices you see in front of you are for broad coverage of gram negative bacteria, which are the most common causes of clinical decompensation in these patients. This is a case example. A 60-year-old male with acute myelogenous leukemia is receiving inpatient induction chemotherapy. On his fifth night in the hospital, the nurse calls you and states that he has a fever of 38.3. His vital signs, including is blood pressure and heart rate, are stable and he’s not hypoxic. What do you do first? The right first thing to do is to go assess the patient. Ask focus questions about their symptoms and do a complete physical exam. In general, it is still recommended to avoid a rectal examine in these patients to avoid more bleeding. You find that he is having normal stools and no new symptoms. Therefore, you order a CBC with the differential and a chemistry panel. You can hold off on a Clostridium difficile toxin, as he’s not clinically having symptoms consistent with this infection. You also would order blood cultures, a urinanalysis, and urine culture as well as a chest x-ray. Once these various labs are drawn, you would start empiric IV cefeprine for broad gram negative coverage and await your lab and micro results. This is a good practice board question developed from one that I saw during my studying. A 45-year-old female with acute myelogenous leukemia is undergoing chemotherapy. One week after induction she develops confusion, a fever, and headache. On physical exam, she’s altered with nuchal rigidity, photophobia, and a positive Kernig sign. Her labs are significant for an ANC of 17o, so she’s certainly neutropenic. A hemoglobin of 7.8 and platelets of 76,000. A lumbar puncture is consistent with bacterial meningitis. Which of the following is most likely pathogen for this patient? A. Toxoplasma. B. Staph aureus. C. Pseudomonas. Or D. H flu? The correct answer is C, pseudomonas. She’s neutropenic and she has signs and symptoms consistent with meningitis. This is confirmed with a study such as the lumbar puncture, and she’s most susceptible to gram negative bacteria, including pseudomonas. One important thing to realize is that staph aureus would be more common in these neutropenic patients if she had a line infection, mucusitis or other evidence of skin cellulidities. In summary, fever in the neutropenic a patient is common and can be the only sign of a severe underlying infection and can be a life-threatening medical problem. A thorough assessment of the patient with a good history and a physical exam are paramount. Lab work and cultures are important additional data to obtain, and immediate empiric antibiotic therapy is essential, particularly gram negative coverage. Some of my key references include the 2010 update by the Infectious Disease Society of America, as well as two other papers important in treatment induced neutropenia. Two main acknowledgements that I have for this talk are for Doctor Carlos De Castro, a hematology oncology professor at Duke University Medical Center. And Doctor Aimee Zaas, who’s also the program director of Internal Medicine and an infectious disease physician. They both were instrumental in this talk.

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1 Comment

  • Reply Bridget the Swagg Master August 14, 2019 at 6:30 am

    Wow.i learned so much.

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