Febrile neutropenia: Clinical sciences

Chapters:

Watch video only

Introduction0:00–1:00

Febrile neutropenia is defined as either a single oral temperature of 101 degrees Fahrenheit or 100.4 degrees lasting an hour or more, both in the setting of an absolute neutrophil count or ANC lower than 1500 cells per microliter, while severe neutropenia is defined as an ANC lower than 500.
Neutropenia is commonly caused by chemotherapy, but it can also result from other medications, autoimmune diseases, or infections.
So, whether or not you confirm the source of infection, you can further classify as febrile neutropenia with confirmed infection or fever of unknown origin, or FUO for short.
Now, if you suspect febrile neutropenia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.

Unstable patient1:00–1:54

If unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and consider starting IV fluids.
Keep in mind that septic patients with febrile neutropenia may have profound hemodynamic instability requiring urgent volume resuscitation.
In addition, put your patient on continuous vital sign monitoring including blood pressure, heart rate, and pulse oximetry, and provide supplemental oxygen if needed.
Finally, don’t forget to start empiric broad-spectrum antibiotics.Alright, now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss the stable ones.

Stable patient1:54–3:28

If your patient is stable, first obtain a focused history and physical examination. Your patient typically reports fever and malaise, as well as symptoms of infection, like a new onset cough, dysuria, diarrhea, or erythema of the skin.
These symptoms usually occur while undergoing chemotherapy, or after starting a medication associated with neutropenia, like carbamazepine or an aminosalicylate.
They may also report a history of a chronic viral infection, like HIV and hepatitis; or an autoimmune disease, such as rheumatoid arthritis or Sjogren syndrome.
On the other hand, physical examination primarily reveals a single oral temperature of 101 degrees Fahrenheit or higher, or a temperature above 100.4 degrees for an hour or more.
In other words, a single oral temperature of 38.3o Celsius or higher, or a temperature above 38o Celsius for an hour or more.
You might also find localized signs of infection, like abnormal breath sounds, suprapubic or abdominal tenderness, or warmth and skin induration.If you notice these findings, you should suspect an infection with neutropenia.

Suspect infection with underlying neutropenia3:28–5:22

Next, order labs, including a CBC with differential, and blood cultures from at least two separate sites. For example, if your patient has a central venous catheter in place, one site should be from the lumen, and the other from a peripheral site.
Depending on the history and physical exam findings, you may also need to order other cultures from urine, stool, CSF, or wound.
Now, here’s a high-yield fact! Do not perform digital rectal examination in patients with suspected or confirmed neutropenia, because of the risk of microtrauma and inadvertent translocation of bacteria into the bloodstream!Now, before you do anything else, start an IV antipseudomonal beta-lactam antibiotic such as cefepime, a carbapenem, or piperacillin-tazobactam.
In fact, the initial dose should be given within the first hour of patient presentation, even if you can’t obtain cultures beforehand.And here’s one clinical pearl to keep in mind!
If your patient has previously been infected or colonized with a resistant organism, or if your hospital has high local resistance rates, consider additional coverage to target resistant pathogens.
Common resistant bacteria include methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus, and extended-spectrum β-lactamase–producing gram-negative bacteria.Once you start an IV antipseudomonal beta-lactam, calculate your patient’s absolute neutrophil count or ANC for short.

Calculate ANC5:22–6:17

This will help you determine if febrile neutropenia is present or not. ANC is determined by multiplying the total WBC count by the percentage of polymorphonuclear and band cells, then dividing this figure by 100.
If you find that ANC is above 1500 cells per microliter, your patient is not neutropenic, so consider alternative diagnoses.
On the other hand, if it is equal to or lower than 1500, you can diagnose febrile neutropenia; while an ANC lower than 500 indicates severe neutropenia, which carries an even higher risk of infections.
Now, if you initially didn’t identify a source of infection during history and physical exam, you should assess for a possible source of infection.

Assess source of infection6:17–6:51

This may involve further testing, such as a viral respiratory panel to assess for viral respiratory tract infections, as well as blood cultures, microscopic urinalysis, and imaging like chest x-ray.
Keep in mind that in most cases the infectious source is not identified. If this further workup reveals the source of infection or the culture comes back positive, diagnose febrile neutropenia with confirmed infection.

Febrile neutropenia with confirmed infection6:51–9:07

Next, modify antibiotic coverage to include a full course of antibiotics targeting the identified pathogen, and then assess response after 2 days.
If the treatment response is adequate, meaning your patient is now afebrile and their symptoms have improved, complete the course of the current antibiotics.
Next, repeat CBC with differential to calculate ANC. If the ANC is above 500, discontinue the antibiotics.
However, if the ANC is less than or equal to 500, you should continue antibiotics until the ANC is at least 500. On the other hand, the treatment response is inadequate if after 2 days your patient still has a fever or symptoms.
In this case, admit your patient to the hospital, revisit the history and physical exam, repeat cultures, and reorder imaging and other studies as appropriate based on the clinical findings.
You should also, consider modifying your patient’s antimicrobial coverage, such as adding antifungals, especially if the fever persists after 4 to 7 days.Now, here’s another high-yield fact!
The most common cause of febrile neutropenia in adults is central line infection in patients receiving chemotherapy. In these individuals, obtain blood cultures through each lumen to determine if catheter removal is necessary.
If it’s just a localized skin infection, and blood cultures grow only coagulase-negative Staph, keep the CVC and start IV vancomycin.
However, if blood cultures are positive for any other pathogen beside coagulase-negative Staph, remove the catheter and give antibiotics based on the sensitivity profile.Alright, now that we’ve covered patients with a confirmed source of infection, let’s go back and discuss patients with febrile neutropenia, with no confirmed source of infection and negative cultures.
In this case, diagnose fever of unknown origin and continue treatment with antipseudomonal beta-lactam.Again, assess your patient’s response to treatment after two days.

FUO9:07–10:57

If there’s an adequate response and fever has resolved, repeat CBC with differential. If the ANC is greater than 500, discontinue antibiotics.
However, if the ANC is 500 or less, continue antibiotics until the ANC is greater than 500.On the other hand, the treatment response is inadequate if the fever persists for more than 2 days.
In this case, admit your patient to the hospital, revisit the history and physical exam, repeat cultures, and reorder imaging and other studies based on the clinical findings.
Again, you should consider modifying your patient’s antimicrobial coverage, such as adding antifungals to the regimen if the fever persists after 4 to 7 days.
You can also consider performing additional imaging to look for the source, such as an invasive fungal infection.Now, here’s one last clinical pearl!
Patients with neutropenia with low risk of complications can be managed at home with oral broad-spectrum antibiotics, such as fluoroquinolone and amoxicillin-clavulanate.
On the other hand, high-risk patients should continue inpatient treatment with empiric broad-spectrum IV antibiotics and close monitoring.
Alright, as a quick recap... If you suspect febrile neutropenia, order a CBC, cultures, and start an antipseudomonal beta-lactam.
Next, calculate the ANC. If it’s 1500 or lower, assess possible infection sources.
If the source is identified or cultures are positive, modify the antibiotic regimen and assess the response in 2 days. If there’s adequate response, repeat CBC and recalculate the ANC.

Review10:57–12:19

If it’s over 500, discontinue antibiotics; otherwise, continue antibiotics until it’s above 500. If there’s inadequate response, admit the patient to the hospital, revisit diagnostic testing, and modifying antimicrobials as appropriate.
If there’s no infection sources and cultures are negative, diagnose fever of unknown origin and continue the antipseudomonal beta-lactam.
Assess the response in 2 days; if fever has resolved, repeat CBC and recalculate ANC. If it’s over 500, discontinue antibiotics; otherwise, continue antibiotics until it’s above 500.
If there is inadequate response admit the patient to the hospital revisit diagnostic testing and modify antimicrobials as appropriate If there is no infection source and cultures are negative diagnose fever of unknown origin and continue the anti pseudomonal beta lactam Assess the response in two days If fever has resolved repeat CBC and recalculate A and C If it's over 500 discontinue antibiotics otherwise
Febrile neutropenia: Video, Causes, and Symptoms | Osmosis