Red flags
- Neutropenia (known or chemotherapy history) -> febrile neutropenia pathway, do not wait for a focus to emerge
- Haemodynamic instability, altered mental state -> sepsis pathway regardless of source found
- Non-blanching rash + fever -> meningococcaemia until excluded
- Returned traveller with fever -> malaria until excluded (can kill within days if missed)
- Immunosuppression (HIV, transplant, biologics, splenectomy) - broadens differential and lowers threshold for empirical treatment
- New murmur + fever -> endocarditis
Differential by mechanism
- Occult UTI/pyelonephritis, early pneumonia, intra-abdominal collection, endocarditis, dental/sinus source, occult line infection
- Malignancy (lymphoma, renal cell, hepatocellular), drug fever, connective tissue disease/vasculitis, thromboembolism (PE/DVT can present as fever), thyrotoxicosis
- Neutropenic: bacterial translocation from gut/skin flora - treat empirically, do not wait for a focus
- Returned traveller: malaria, typhoid, dengue, rickettsial disease - destination and exposure history changes the entire differential
- Immunosuppressed/HIV: opportunistic infection expands the differential substantially (see HIV-related notes)
- Post-operative: the "5 Ws" - Wind (pneumonia/atelectasis), Water (UTI), Wound, Walking (DVT/PE), Wonder drugs (drug fever) - timed roughly to days post-op
Focused history
- Fever pattern, duration, associated symptoms (even subtle - night sweats, weight loss, localising pain)
- Travel history - destination, dates, prophylaxis, exposures (fresh water, animals, food, sexual contacts)
- Immunosuppression - HIV status, chemotherapy, biologics, transplant, splenectomy, recent steroid use
- Recent procedures, hospitalisation, antibiotic use, indwelling devices
- Animal/occupational/recreational exposures (farms, ticks, unpasteurised products)
- Sexual history, IV drug use
- Full medication review - drug fever is a diagnosis of exclusion but common
Focused examination
- Full systematic exam - skin (rash, petechiae, splinter haemorrhages), lymphadenopathy, cardiac auscultation (new murmur), abdominal exam, joints
- Line sites, surgical wounds, pressure areas
- Fundoscopy (Roth spots), nail beds, palms/soles (endocarditis stigmata)
- Lymphoreticular exam (hepatosplenomegaly) if malignancy/systemic infection suspected
- Repeat examination if initial exam unremarkable - findings can evolve
Investigation strategy
- First-line: FBE with differential, UEC, LFT, CRP, blood cultures (x2 sets), urine MCS, CXR
- Directed by exposure history: malaria thick/thin films (repeat x3 if negative and suspicion remains), blood culture held longer if suspecting fastidious organisms (endocarditis - HACEK), serology per travel/exposure
- Echocardiography if new murmur or unexplained bacteraemia
- CT imaging (chest/abdomen/pelvis) if no focus found after initial work-up and patient remains unwell
- Do not over-image or over-culture a well patient who defervesces spontaneously - most short-lived undifferentiated fevers are self-limiting viral illness
Management
1. Risk-stratify first - neutropenic, septic, or high-risk exposure (malaria) patients get empirical treatment immediately, not sequential work-up
2. Well, immunocompetent patient with no red flags: symptomatic management and safety-netting is often appropriate while first-line investigations return - most resolve spontaneously (viral)
3. Persistent fever without a focus (>1 week) despite initial work-up: consider the diagnosis as pyrexia of unknown origin (PUO) - escalate imaging, consider malignancy/rheumatological work-up, infectious diseases referral
- Suspected malaria: treat empirically if severe/high-risk exposure while confirmation pending, per antimalarial guidelines
- Suspected meningococcaemia: immediate IV ceftriaxone/benzylpenicillin before any confirmatory test
- Neutropenic fever: immediate broad-spectrum antibiotics (see Febrile neutropenia note)
- Otherwise avoid "blind" broad-spectrum antibiotics in a stable patient without a source - masks culture yield and drives resistance without proven benefit
- Safety-netting advice and early review if fever persists or new symptoms develop
- Specialist infectious diseases input for prolonged/unexplained fever
Traps
- Missing malaria in a returned traveller because fever pattern was atypical or rapid antigen test was falsely negative on a single sample
- Starting broad-spectrum antibiotics reflexively in a well patient with undifferentiated fever, obscuring the diagnosis and driving resistance
- Missing neutropenia because a recent FBE was not checked in a chemotherapy patient presenting with fever
- Attributing fever to a urinary source based on asymptomatic bacteriuria alone
- Not repeating examination/investigations when the initial work-up is unrevealing but the patient remains unwell
Talk track
Risk-stratify before investigating in detail - neutropenia, sepsis, or a high-risk travel/exposure history (malaria, meningococcaemia) trigger immediate empirical treatment rather than sequential work-up. In a well, immunocompetent patient with no red flags, most undifferentiated fever is self-limiting viral illness and does not need blind broad-spectrum antibiotics. Persistent fever beyond about a week despite first-line work-up becomes a pyrexia of unknown origin problem needing broader imaging and specialist input rather than repeating the same tests.
Study aid only. These notes are written with the help of AI. Not for guiding clinical decisions.