Neutropenic fever

72F with CML had persistent fever ~102F, cough. CT chest with focal consolidation in LLL. Sputum cx: Klebsiella pneumoniae. Serum BDG, GM negative.

Was on Vanc/Cefepime/LAmB, now narrowed to Cefepime + afebrile 24h

Duration of Cefepime?
#IDTwitter #IDMedEd #IDFellows

Today’s #tweetorial is on fever + neutropenia!

Background:
Up to 50% pts with solid tumors & >80% pts with hem malignancy will develop fever during chemo cycle assoc’d with neutropenia
Only 20-30% of these identify clinical infection
Only 10-25% bacteremia

Clapping Yay GIF

The very basics:
🔹Here is the classic article from 1966 that demonstrated ⬆️susc to infection as neutrophils<500
🔹Freq and severity of infection inversely proportional to neutrophil count
🔹Risk of severe infection and BSI greatest at ANC <100

https://pubmed.ncbi.nlm.nih.gov/5216294/

Now setting the definitions straight:
🌡️Fever = Single temp >=38.3C or >=38 sustained over 1 hr period
💠Neutropenia = <500 neutrophils/microL or <1000 with predicted decline to <500 over next 48 hrs

First Q: Can pts ever be treated outpatient with PO abxs for F&N?

🔹Possibly, if anticipate brief neutropenia + no/few co-morbidities
🔹High vs low risk according to NCCN + IDSA guidelines are below (notice a lot of overlap)
🔹In addition, there is a formal risk classification = MASCC score (👇for details)
▪️Low risk >=21
▪️High risk <21

Initial empiric F&N tx (NCCN/IDSA) = monotherapy w/ anti-pseudomonal beta-lactam:
🔸Cefepime, Imi/Cilast, Mero, Pip-Tazo
🔸Ceftaz (but NCCN category 2B, ⬇️GPC activity, ⬆️breakthrough inf)

Oral abxs if low-risk: Cipro+Amox/Clav, Moxiflox, Levoflox

But also think about👇

Why target with anti-pseudomonal therapy?
🔸Goal of initial empiric therapy = prevent serious M&M fr bact until further cx data available
🔸GN organisms, esp Pseudomonas, associated with high complication and mortality rate
🔸Highlighted below:

https://pubmed.ncbi.nlm.nih.gov/17689933/

When to consider additional GP coverage (see image below)

Now, when to consider stopping this GP tx?
Should discontinue 2-3d later if no GP organism is identified! Study about this in next tweet

https://pubmed.ncbi.nlm.nih.gov/2019772/
747 F&N pts randomized to ceftaz+amikacin +/- vanc as initial therapy
🔹No diff by tx regimen in proportion of febrile pts on each day or in fever duration
🔹No pt with GP BSI died during 1st 3d
🔹⬆️nephrotox if tx’d with vanc (6% vs 2%)

Duration of abxs are dictated by the organism and site of infection.

Recommendations on when to de-escalate in those with w/o source varies slightly by organization 👇

So, what is safety of early d/c of abxs in these pts vs continuing until resolution of neutropenia??

There is a Cochrane review of this that examined 8 RCTs. Between short vs long abxs arms, no difference in all-cause mortality, rates of clinical failure, incidence of BSI – but made no strong conclusions as evidence is limited by imprecision, selection bias, variable defns

2 papers you can look at when thinking about feasibility and safety of short term abx treatment:

How Long study (was included in Cochrane review)
https://pubmed.ncbi.nlm.nih.gov/29153975/

ANTIBIOSTOP study

https://pubmed-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/29451055/

At the end of the day, the key to approaching F&N is individualizing your evaluation:
➡️What ppx prior to admission
➡️Patient clinical status
➡️New medications
➡️Expected duration of neutropenia
➡️Next chemotherapy scheduled
➡️Timing of infection risk