Lecture 3 - Pyrexia of Unknown Origin

Question 1

Learning Outcomes

Answer 1

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

Question 2

Define Fever

Answer 2

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

Question 3

Define a Fever of Unknown Origin

Answer 3

• > 38.3 degrees
• several occasions
• continues for more than 3 weeks, DESPITE 1 week of evaluation

Question 4

What is the most common cause of FUO

Answer 4

Infection

Question 5

List a few other important causes of FUO

Answer 5

• • Malignancies
• Auto Immune Diseases
• *non infectious causes must be differentiated from infections in patients with FUO upon examination

Question 6

In what percentage of patients have an FUO without probable cause

Answer 6

5-15%

Question 7

List the 4 categories of FUO

Answer 7

Classical

Nomocomial (hospital aquired)

Neutropenic

HIV - associated

Question 8

Define Classical FUO

Answer 8

• <38.3 degrees
• Several times
• More than 3 week duration

Question 9

Define Nosocomial FUO

Answer 9

• >38.3 degrees
• Several times
• Hospitalized

Question 10

Define Neutropenic FUO

Answer 10

• >38.3 degrees
• Several times
• Neutrophil Count is <500/mm3

Question 11

Define HIV - associated FUO

Answer 11

• >38.3 degrees
• HIV positive

Question 12

List bacterial examples of infection

Answer 12

• TB
• Enteric Fever
• Ostemyelitic
• Endocarditis
• Brucellosis
• Abcess (intra-abdominal)
• Billiary System Infection
• Urinary Tract Infection
• Lyme Disease
• Leptospiros
• Q fever
• Typhus

Question 13

Name the cause of each PARASITIC infection

1. Malaria
2. Amoebic Abcesses
3. Toxoplasmosis

Answer 13

1. Plasmodium Species
2. Entamoaeba Histolytica
3. Toxoplasma Gondii

Question 14

Name the Cause of Each Fungal Infection

1. Candidiasis
2. Histplasmosis

Answer 14

1. Candida Albicans
2. Histoplasma Capsulatum

Question 15

Name examples of Viral Infections

Answer 15

• Hepatitis
• AIDS
• Infectious Mononucleosis

Question 16

Explain the 2 divisions of Aetiology

Answer 16

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

Question 17

List the groups of people who may suffer severe infections WITHOUT presenting with pyrexia

Answer 17

• Seriously ill neonates
• Elderly
• Patients with uraemia
• Patients on corticosteroids
• Patients on continous anti-pyretic therapy

Question 18

Due to the extensive nature of Infections, name the first steps in investigation of the cause

Answer 18

• Extensive History
• Examination
• Screening Tests

Question 19

Outline the necessary Questions to be asked in a History

Answer 19

• Travel
• Occupation
• Hobbies
• Exposure to animals
• Known infectious hazards
• AB therapy within the previous 2 months
• Substance Misuse
• Other Habits

Question 20

Why is a travel history important

Answer 20

Some Infections are…

1) Zoonosis

• Leptospirosis
• Spotted Fevers

2) Vector Borne

• Malaria
• Trypanasmosis

3) Limited to Geographic Distribution

• Histoplasmosis

Question 21

Highlight the key components of an examination

Answer 21

• • Eyes
• Hands
• Face
• Lymph Nodes
• Abdomen
• Ausculatation of Heart

Question 22

What is the minimum diagnostic evaluation necessary to diagnose FUO (Classical)

Answer 22

• 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

Question 23

Give Examples of FURTHER evaluations that can be done to confirm FUO

Answer 23

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

Question 24

Explain the typical causes of Nosocomial FUO

Answer 24

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

Question 25

Explain the typical causes of **Neutropenic FUO**

Answer 25

**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

Question 26

Explain the typical causes of HIV - associated FUO

Answer 26

**1) Respiratory tract** * Pneumocystis * Mycobacterium **2) Central nervous system** * Toxoplasma **3) Gastrointestinal trac**t * Salmonella * Campylobacter * Shigella **4) Genital tract** * Treponema pallidum * Neisseria gonorrhoeae

Question 27

Explain the Pathogenesis of Endocardiditis Name the Most common cause where it comes from Give an example Comment on Fibrin

Answer 27

* 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.

Question 28

Infective Endocarditis: Patient Profile

Answer 28

**Majority of patients have...** * Pre-existing heart defect * \*Either congenital or Aquired (as a result of Rheumatic Fever) * Prosthetic heart valve in-situ

Question 29

Explain the common causes of Infective Endocarditis

Answer 29

* Almost any organism can cause Endocarditis * BUT native valves are almost are usually infected by **oral streptococci or staphylococci**

Question 30

Infective Endocarditis: Clinical Presentation

Answer 30

**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

Question 31

In ADDITION to a fever and a heart murmur, what other symptoms may patients complain of 1) Non specific 2) Peripheral Manifestation 3) Other

Answer 31

**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

Question 32

Comment on the mortality of EC, pre and post AB

Answer 32

Pre AB = 100% Post AB = 20-50% \* AB resitance has developed

Question 33

How long will it take to eradicate the infection, why is this and comment on relapse

Answer 33

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

Question 34

List the causative organisms associated with Endocarditis 1) Native Valve 2) Early Prosthetic Valve 3) Late Prosthetic Valve

Answer 34

**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

Question 35

Explain the neccessary Investigations completed to diagnose endocarditis

Answer 35

* **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.

Question 36

Comment on **culture negative** endocarditis

Answer 36

* Difficult to grow organisms * Antibiotic presence * Q fever (Coxiella burnetii)

Question 37

**Treatment** ## Footnote 1. What does the type of AB depend on 2. Virdans Streptococci 3. Enterococci 4. Staphylococci 5. Duration

Answer 37

**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

Question 38

Case ## Footnote 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?**

Answer 38

* Blood culture * To be done whilst she is febrile * AB treatment can wait until patient sensitivites have been determined