Febrile neutropenia: Clinical sciences

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.

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.

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. 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. 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.