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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
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
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
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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/
The very basics:
Here is the classic article from 1966 that demonstrated susc to infection as neutrophils<500Freq and severity of infection inversely proportional to neutrophil countRisk of severe infection and BSI greatest at ANC <100https://pubmed.ncbi.nlm.nih.gov/5216294/
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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?
Now setting the definitions straight:
Fever = Single temp >=38.3C or >=38 sustained over 1 hr periodNeutropenia = <500 neutrophils/microL or <1000 with predicted decline to <500 over next 48 hrsFirst Q: Can pts ever be treated outpatient with PO abxs for F&N?
5/
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
Possibly, if anticipate brief neutropenia + no/few co-morbiditiesHigh 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 >=21High risk <21
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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
Initial empiric F&N tx (NCCN/IDSA) = monotherapy w/ anti-pseudomonal beta-lactam:
Cefepime, Imi/Cilast, Mero, Pip-TazoCeftaz (but NCCN category 2B, GPC activity, breakthrough inf)Oral abxs if low-risk: Cipro+Amox/Clav, Moxiflox, Levoflox
But also think about
7/
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/
Why target with anti-pseudomonal therapy?
Goal of initial empiric therapy = prevent serious M&M fr bact until further cx data availableGN organisms, esp Pseudomonas, associated with high complication and mortality rateHighlighted below:https://pubmed.ncbi.nlm.nih.gov/17689933/
8/
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
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
9/
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%)
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 durationNo pt with GP BSI died during 1st 3dnephrotox if tx'd with vanc (6% vs 2%)
10/
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??
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??
11/
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
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
12/
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/
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/
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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
At the end of the day, the key to approaching F&N is individualizing your evaluation:
What ppx prior to admissionPatient clinical statusNew medicationsExpected duration of neutropeniaNext chemotherapy scheduledTiming of infection risk
14/
IDSA GL: https://academic.oup.com/cid/article/52/4/e56/382256
NCCN GL: http://NCCN.org
ECIL GL: https://pubmed.ncbi.nlm.nih.gov/24323983/
IDSA GL: https://academic.oup.com/cid/article/52/4/e56/382256
NCCN GL: http://NCCN.org
ECIL GL: https://pubmed.ncbi.nlm.nih.gov/24323983/
Today's #IDFellows #Tweetorial is brought to you by @swinndong from @BIDMC_IDFellows!
@wuIDq @IUIDfellowship @UAB_ID @yaleIDfellows @templeID1 @VUMC_IC @MayoclinicINFD @MGH_ID @MontefioreID @UNMC_ID @UVA_ID @OhioState_ID @UTSWinfDis @BrownIDprogram @RushCCH_ID @OHSU_ID
@wuIDq @IUIDfellowship @UAB_ID @yaleIDfellows @templeID1 @VUMC_IC @MayoclinicINFD @MGH_ID @MontefioreID @UNMC_ID @UVA_ID @OhioState_ID @UTSWinfDis @BrownIDprogram @RushCCH_ID @OHSU_ID
