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Patient handout

Fever of unknown origin (FUO)

PRODUCTION

1. Your condition

This handout is for fever of unknown origin (fuo). Your care team identified this based on: classic fuo — fever >38.3°c ≥3 wk + diagnostic uncertainty after 3 outpatient visits or 1 wk inpatient (petersdorf 1961 pmid 31271266; durack-street 1991 pmid 1651090).

Other reasons your team may use this plan: nosocomial fuo — hospitalized ≥24 h, fever onset post-admission, no infection on admission (durack-street 1991 pmid 1651090 — dvt/pe, drug fever, c diff, line/surgical site); neutropenic fuo — anc <500 + fever (idsa 2010 pmid 21205990; asco/idsa 2018 pmid 29461916 — emergent empiric within 1 h); hiv-associated fuo — cd4-stratified opportunistic infection / iris / lymphoma differential (durack-street 1991 pmid 1651090).

2. Your medications

Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.

MedicationStarting doseHowWhenWhat it does
cefepime2 g IVIVq8h (renal-dose adjusted)IDSA 2010 PMID 21205990 + ASCO/IDSA 2018 PMID 29461916 — first-line antipseudomonal monotherapy for neutropenic fever; within 1 h of presentation
vancomycin15-20 mg/kg IVIVq8-12h, target AUC 400-600IDSA 2010 — add for empiric MRSA / coag-negative staph in unstable / line-associated / soft tissue
ceftriaxone2 g IVIVBID for endocarditis empiricAHA 2023 infective endocarditis empiric pending culture; obtain ≥3 cultures FIRST
prednisone1 mg/kg PO (typically 60 mg)POdailyDo NOT delay vision-saving steroid in arteritis; biopsy still positive within 7-14 d (Mulders-Manders ESCMID 2019 PMID 31271266)
micafungin100 mg IVIVdailyIDSA 2010 PMID 21205990 + ASCO/IDSA 2018 PMID 29461916 — empiric antifungal for persistent neutropenic fever ≥4 d on broad-spectrum antibiotics

Plan: Empiric coverage axis — restricted to neutropenic fever, suspected unstable endocarditis, strong GCA (IDSA 2010 PMID 21205990; ASCO/IDSA 2018 PMID 29461916; AHA 2023; ESCMID 2019 PMID 31271266)

3. When to call your provider

Contact your care team if any of the following happen:

  • New hemodynamic instability → ED
  • Neutropenia (ANC <500) → ED for cefepime ± vancomycin within 1 h (IDSA 2010 PMID 21205990)
  • Suspected endocarditis with embolic phenomena → admit
  • HLH features (ferritin >10000 + cytopenias) → ED
  • Returned-traveler with bleeding / altered consciousness → ED + CDC notification

4. When to seek emergency care

Call 911 or go to the nearest emergency room right away if you have:

  • Neutropenic FUO — ANC <500 + fever ≥38.3°C — emergent empiric antibiotics within 1 h (IDSA 2010 PMID 21205990; ASCO/IDSA 2018 PMID 29461916)(life-threatening)
  • HIV-associated FUO — CD4-stratified DDx (opportunistic infection / IRIS / lymphoma) (Durack-Street 1991 PMID 1651090)
  • Returned-traveler FUO — geographic exposure → malaria / typhoid / VHF / rickettsial (Wright NEJM 2022; CDC reporting)
  • New murmur + persistent bacteremia OR IVDU + fever OR embolic phenomena (AHA 2023 endocarditis Class I) — route cardio.infective-endocarditis.core.v1
  • B-symptoms (fever + drenching night sweats + weight loss >10%) + pathologic adenopathy ≥1.5 cm or supraclavicular — co-route symptom.lymphadenopathy.v1
  • HLH/MAS — ferritin >10000 + cytopenias ≥2 lineages + splenomegaly + elevated LDH/sIL2R + hypertriglyceridemia / hypofibrinogenemia(life-threatening)
  • Age ≥50 + ESR ≥50 + headache + visual change OR jaw claudication (Mulders-Manders ESCMID 2019 PMID 31271266)
  • IGRA positive + chronic fever + weight loss + cough OR endemic exposure (ATS/IDSA 2016)

5. Follow-up

Repeat workup if undiagnosed; ~20% self-resolve without diagnosis; specialty referrals (rheum, oncology, ID); 4-wk reassessment if undiagnosed

6. Sources

Guideline: Petersdorf NEJM 1961 (PMID 31271266) + Durack-Street 1991 modern classification + Mulders-Manders ESCMID 2019 Diagnostics (PMID 31271266) + Ergul PET-CT FUO 2014 (PMID 29567271) + Bleeker-Rovers PET-CT FUO 2007 (PMID 17220753) + IDSA Neutropenic Fever 2010 (PMID 21205990) + ASCO/IDSA Neutropenic 2018 (PMID 29461916) + Yamaguchi AOSD 1992 (PMID 1578458) + Wright NEJM FUO 2022

  1. pubmed.ncbi.nlm.nih.gov/31271266
  2. pubmed.ncbi.nlm.nih.gov/1651090
  3. pubmed.ncbi.nlm.nih.gov/29567271