As an intern, one of the highest-yield schemas I learned was for persistent fevers despite treatment with abx.
I use it all the time as a resident, especially when working with cancer patients.
Let's go through it!
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The general ddx for persistent fevers in the hospital, despite abx:
1. Wrong bug
2. Wrong drug
3. Wrong process
4. No source control
5. Not enough time
Let's take them one at a time.
1. Wrong Bug
When giving abx, we assume it's bacterial, but after some time, you should also consider:
- viruses - ex: CMV, EBV, HBV, HCV
- fungi - ex: candida, aspergillus, PJP, etc
- atypical infections - tickborne, TB, etc.
In neutropenic fever, if a patient has been fevering for 4–7 days despite BSA, it may be reasonable to broaden to fungal coverage.
Voriconazole and posaconazole are preferred.
Fluconazole is saved for known candida, as it does not cover endemic mycoses or Aspergillus.
Some factors that may push you toward broadening to fungal coverage include:
- positive BDG
- severe sepsis
- CT with GGOs and/or nodules
- prolonged ANC <500
- TPN use
Though not part of the guidelines, one common misstep is not covering for atypicals.
Ex: A patient comes in sick and gets typical BSA with vanc/zosyn.
Only a few days later does someone bring up that our abx selection, though broad, has some gaps (i.e azithro or doxy)
2. Wrong Drug
This is most commonly due to MDROs.
Some examples and common treatments:
- ESBL GNRs - carbapenem
- VRE - daptomycin or linezolid
- Carbapenem-res PsA - many options (ceftaz-abi, mero-vabor, cefidericol, etc.)
- Candida Kruseii - voriconazole
It can be intimidating to reach for these big guns since most of us don't have much experience with them.
If you think you have an MDRO or if cultures show that you do, consult ID for advice on the best agent and antibiotic stewardship.
#IDTwitter - Any pearls on MDROs?
3. Wrong Process (not infectious)
Many things other than infections can cause fevers (especially in cancer patients).
Here are just a few:
- Drug fever
- Malignancy
- Transfusion reaction
- Thrombophlebitis
- Autoimmune Disease
In neutropenic fever, it's particularly unfair that cancer itself, the needed transfusions, clots (which all cancer patients are susceptible to), and the antibiotics meant to address the fevers in the first place, can all be the culprit.
twitter.com/ROKeefeMD/status/1617567957445672961
Some common drugs that can cause fevers:
- Antibiotics - penicillins, cephalosporins
- AEDS - ex: phenytoin, carbamazepine
- Anti-neoplastics
- Allopurinol
4. No Source Control
This is a common reason for an infectious cause of FUO.
Imaging can be helpful for localizing a source.
In particular, you should think about:
- endocarditis
- CLABSI
- osteomyelitis
- liver/abdominal abscesses
Do know that blood culture-negative endocarditis (BCNE) does happen, often due to getting abx before BCx draws.
Other causes:
- Coxiella burnetti
- Bartonella (quintana/henselae)
ncbi.nlm.nih.gov/pmc/articles/PMC5708915/
5. Not Enough Time
Even with the right treatment, fevers can last for a few days. This is especially true for diseases that are hard to treat and require prolonged courses of abx, like endocarditis or osteomyelitis.
Fevers caused by a virus can last for several days as the body goes through its natural process.
It can be challenging to sit on your hands in these situations, but it's often the right choice if the patient is stable!
Lastly, though not part of the schema, you should be mindful of fevers 2/2 a new infection from the iatrogenic spread of respiratory viruses!
If it seems new or the patient has URI symptoms, repeat that RVP!
In general, after thinking through the schema, the decision to broaden abx or go digging for a source is dependent on clinical judgment, the patient's status, and their risk of decompensation.
It's one of the many gray areas in medicine where there is no easy answer!