Lecture 3 - Pyrexia of Unknown Origin Flashcards
Learning Outcomes
Define FUO (Classical and risk group). Describe the diagnostic evaluation of FUO. List the key pathogens in specific patient groups. Describe the presentation, investigation and antibiotic treatment of infective endocarditis
Define Fever
A common complaint of patients presenting to a doctor. The cause is usually immediately apparent or is discovered within a few days, or the temperature settles spontaneously.
- Exogenous or endogenous pyrogens
- Common Symptom - May have a protective effect
Define a Fever of Unknown Origin
- > 38.3 degrees
- several occasions
- continues for more than 3 weeks, DESPITE 1 week of evaluation
What is the most common cause of FUO
Infection
List a few other important causes of FUO
- Malignancies
- Auto Immune Diseases
- *non infectious causes must be differentiated from infections in patients with FUO upon examination
In what percentage of patients have an FUO without probable cause
5-15%
List the 4 categories of FUO
Classical
Nomocomial (hospital aquired)
Neutropenic
HIV - associated
Define Classical FUO
- <38.3 degrees
- Several times
- More than 3 week duration
Define Nosocomial FUO
- >38.3 degrees
- Several times
- Hospitalized
Define Neutropenic FUO
- >38.3 degrees
- Several times
- Neutrophil Count is <500/mm3
Define HIV - associated FUO
- >38.3 degrees
- HIV positive
List bacterial examples of infection
- TB
- Enteric Fever
- Ostemyelitic
- Endocarditis
- Brucellosis
- Abcess (intra-abdominal)
- Billiary System Infection
- Urinary Tract Infection
- Lyme Disease
- Leptospiros
- Q fever
- Typhus
Name the cause of each PARASITIC infection
- Malaria
- Amoebic Abcesses
- Toxoplasmosis
- Plasmodium Species
- Entamoaeba Histolytica
- Toxoplasma Gondii
Name the Cause of Each Fungal Infection
- Candidiasis
- Histplasmosis
- Candida Albicans
- Histoplasma Capsulatum
Name examples of Viral Infections
- Hepatitis
- AIDS
- Infectious Mononucleosis
Explain the 2 divisions of Aetiology
1. Specific Pathogens
- TB and Typhoid fever caused by specific pathogens
2. Variety of Different pathogens
- UTI
- Billiary Tract Infections
- Abcesses
- *all may be caused by different organisms
List the groups of people who may suffer severe infections WITHOUT presenting with pyrexia
- Seriously ill neonates
- Elderly
- Patients with uraemia
- Patients on corticosteroids
- Patients on continous anti-pyretic therapy
Due to the extensive nature of Infections, name the first steps in investigation of the cause
- Extensive History
- Examination
- Screening Tests
Outline the necessary Questions to be asked in a History
- Travel
- Occupation
- Hobbies
- Exposure to animals
- Known infectious hazards
- AB therapy within the previous 2 months
- Substance Misuse
- Other Habits
Why is a travel history important
Some Infections are…
1) Zoonosis
- Leptospirosis
- Spotted Fevers
2) Vector Borne
- Malaria
- Trypanasmosis
3) Limited to Geographic Distribution
- Histoplasmosis
Highlight the key components of an examination
- Eyes
- Hands
- Face
- Lymph Nodes
- Abdomen
- Ausculatation of Heart
What is the minimum diagnostic evaluation necessary to diagnose FUO (Classical)
- Comprehensive history (including travel, STI risk, hobbies, pets, occupation etc.)
- Comprehensive physical examination (including temporal arteries, ENT, rectal examination, etc.)
- Routine blood tests (FBP, ESR,CRP)
- Cultures of blood, urine
- Chest radiograph &
Abdominal ultrasound
- Antinuclear and antineutrophilic cytoplasmic antibodi, rheumatoid factor
Give Examples of FURTHER evaluations that can be done to confirm FUO
Directed by abnormalities detected by above test
- HIV antibodies depending on detailed history
- CMV-IgM and EBV serology in case of abnormal differential WBC count
- Abdominal or chest helical CT scan
- Echocardiography in case of cardiac murmur
Explain the typical causes of Nosocomial FUO
1) Vascular Line Related - Staphylococci
2) Cholecystitis and Pancreatitis - Gram negative rods
3) Pneumonia (related to assisted ventillation) - Gram negative rods (psuedomonas)
4) Post-Op abcesses (Intra-abdominal) - Gram negative rods, anerobes
Explain the typical causes of Neutropenic FUO
1) Vascular Line Related
- Staphylococci
2) Oral Infection
- Candida
- Herpes SImplex Virus
3) Pneumonia
- Candida
- CMV
- Gram negative rods
- Aspergillus
4) Soft tissue
- peri-anal abcess - Mixture of anaerobes and aerobes
Explain the typical causes of HIV - associated FUO
1) Respiratory tract
- Pneumocystis
- Mycobacterium
2) Central nervous system
- Toxoplasma
3) Gastrointestinal tract
- Salmonella
- Campylobacter
- Shigella
4) Genital tract
- Treponema pallidum
- Neisseria gonorrhoeae
Explain the Pathogenesis of Endocardiditis
Name the Most common cause
where it comes from
Give an example
Comment on Fibrin
- Endogenous infection acquired when organisms entering the bloodstream establish themselves on the heart valves.
- Most commonly streptococci from the oral flora enter the bloodstream,
- For example during dental procedures or vigorous teeth cleaning or flossing
- Fibrin-platelet vegetations are present on damaged valves before the organisms implant, organisms multiply and attract further fibrin and platelet deposition.
Infective Endocarditis: Patient Profile
Majority of patients have…
- Pre-existing heart defect
- *Either congenital or Aquired (as a result of Rheumatic Fever)
- Prosthetic heart valve in-situ
Explain the common causes of Infective Endocarditis
- Almost any organism can cause Endocarditis
- BUT native valves are almost are usually infected by oral streptococci or staphylococci
Infective Endocarditis: Clinical Presentation
Almost Always:
Fever - Heart Murmur
Also, Related to 4 ongoing Processes:
1) Infectious process on the valve and the local intracardiac complications
2) Septic Embolisation
3) Bacteremia, often with metastatic focci of infection
4) Circulating Immune Complexes and other factors
In ADDITION to a fever and a heart murmur, what other symptoms may patients complain of
1) Non specific
2) Peripheral Manifestation
3) Other
Non- Specific
- Weight loss
- Anorexia
- Malaise
- Chills -
- Nausea -
- Vomiting -
- Night sweats
Peripheral Manifestations
- Splinter Hemmorhage
- Osler’s Nodes
Other
- Microscopic haematuria due to immune complex deposition in the kidney
Comment on the mortality of EC, pre and post AB
Pre AB = 100%
Post AB = 20-50% *
AB resitance has developed
How long will it take to eradicate the infection, why is this and comment on relapse
Eradication takes several weeks to achieve
Due to:
- Inaccessibility of the organisms within the vegetations (both to antibiotics and to host defenses) -
- The organism’s high population density and relatively slow rate of multiplication
- Antibiotics work best on rapidly dividing bacteria *Relapse is NOT COMMON
List the causative organisms associated with Endocarditis
1) Native Valve
2) Early Prosthetic Valve
3) Late Prosthetic Valve
1) Native valve
- Oral streptococci (viridans group) such as Streptococcus sanguis - Strep. oralis - Strep. mitis - Staph. aureus.
- *Intravenous drug misusers have the added complication of infection due to organisms they inject into themselves. (gram negatives)
2) Early prosthetic valve
- Coagulase-negative staphylococci are common causes of endocarditis and are probably acquired at the time of surgery.
3) Late prosthetic valve
- More than 3 months after cardiac surgery like those causing native valve endocarditis
Explain the neccessary Investigations completed to diagnose endocarditis
- Blood culture = most important test
- Ideally, three separate samples of blood should be collected within a 24-h period and before antimicrobial therapy is administered.
- Isolation of the causative organism is essential so that antibiotic susceptibility tests can be performed and optimum therapy prescribed.
Comment on culture negative endocarditis
- Difficult to grow organisms
- Antibiotic presence
- Q fever (Coxiella burnetii)
Treatment
- What does the type of AB depend on
- Virdans Streptococci
- Enterococci
- Staphylococci
- Duration
1. Susceptibility of the organ
2. Virdans Streptococci
- Penicillin susceptible streptococci use high doses of penicillin
- Penicillin + Aminoglycoside
3. Enterococci
- Amoxicillin and Aminoglycoside
4. Staphylococci
- Flucloxicillin and aminoglycoside
- Vancomycin
5. Duration
- 4 Weeks
- 6 Weeks if prosthetic valve
- Monitor CRP for response to therapy
Case
75 years-old lady presents with 1 week of
Malaise, nausea loss of appetite
Past history of aortic valve surgery
On examination
Flushed, temp=38.2oC
Systolic murmur
What investigations?
- Blood culture
- To be done whilst she is febrile
- AB treatment can wait until patient sensitivites have been determined
