L08 - Treatment of Respiratory Infections (inc. TB)

Question 1

Define CAP

Answer 1

Community Acquired Pneumonia

Question 2

Give four examples of groups in which CAP is more common

Answer 2

Males
The elderly
Alcoholics
Chronic disease sufferers

Question 3

What proportion of CAP do conventional bacteria cause?

Answer 3

60-80%

Question 4

What proportion of CAP do ‘atypical’ bacteria cause?

Answer 4

10-20%

Question 5

What proportion of CAP do viruses cause?

Answer 5

10-20%

Question 6

What two conventional bacteria are frequently implicated in CAP?

Answer 6

S. pneumoniae

H. influenzae

Question 7

What three ‘atypical’ bacteria are frequently implemented in CAP?

Answer 7

M. pneumoniae
C. pneumoniae
L. pneumophila

Question 8

What four microbiological investigations are most commonly used in diagnosis of CAP?

Answer 8

Sputum analysis/culture
Immunofluorescence on sputum samples
Blood cultures
Urinary pneuomococcal/legionella antigen

Question 9

What three factors is antimicrobial management for CAP based on?

Answer 9

Assessment of likely pathogen
Severity
Likelihood of drug resistance

Question 10

What is CURB65?

Answer 10

CURB65 is a scoring system for CAP:
Confusion MMT <8
Urea >7mmol/l
Resp. rate >30/min
Blood pressure <90 (s) or <60 (d)
65 y/o

Question 11

What is the treatment regimen for a low severity CAP score (0-1)?

Answer 11

Amoxicillin 500mg q.d. for 7 days OR
Doxycyline 200mg (LD) then 100 mg o.d.
If unable to take oral therapy can give i.v. Amoxicillin

Question 12

What is the treatment regimen for a moderate severity CAP score (2)?

Answer 12

Amoxicillin 500mg q.d. for 7 days + Clarithromycin 500mg b.d. for 7 days OR Doxycyline 200mg (LD) then 100 mg o.d.
If unable to take oral therapy can give i.v. Benzyplenicillin

Question 13

If patients are allergic to penicillin what antibiotics can be prescribed instead? - CAP Score <2

Answer 13

Mild - i.v. Cefuroxime 1.5g t.d. (+ i.v. Clarithromycin 500mg b.d.)
Severe - Ciprofloxacin 400mg b.d. + Vancomycin

Question 14

What is the treatment regimen for a severe CAP score (3)?

Answer 14

Co-amoxiclav 1.2g t.d. + Clarithromycin 500mg b.d. for 10 days

Question 15

If patients are allergic to penicillin what antibiotics can be prescribed? - CAP Score >3

Answer 15

Levofloxacin 500mg b.d. + Vancomycin 1g b.d. for 10 days

Question 16

If MRSA is likely what antibiotics should be prescribed?

Answer 16

Levofloxacin 500mg b.d. + Vancomycin 1g b.d. for 10 days

Question 17

In what cases should the time course of the treatment be extended?

Answer 17

Infection with:
Legionella
Staphylococcal
Gram-ve Pneumonia
Extend to 14-21 days

Question 18

When should Mycoplasma infection be suspected?

Answer 18

Young patient
Long prodrome
Pactchy consolidation (CXR)
Extra-pulmonary disease

Question 19

How should Mycoplasma infection be treated?

Answer 19

Tetracyclines for >14 days

Question 20

When is CAP caused by S. aureus more likely?

Answer 20

During an influenza outbreak

Question 21

How should CAP caused by S. aureus be treated?

Answer 21

Flucloxacillin 2g i.v. q.d. ADDED to standard regimen

Question 22

When should Legionellosis be suspected?

Answer 22

Severe CAP (outbreak)
Multi-lobe involvement (CXR)
Hyponatraemia
Focal neurological disease

Question 23

How should Legionellosis be treated?

Answer 23

High dose macrolide (up to 4mg Erythromycin per day) + Rifampicin 600mg b.d.

Question 24

What bacterium causes TB?

Answer 24

M. tuberculosis

Question 25

What proportion of the world is infected with M. tuberculosis?

Answer 25

1/3

Question 26

What racial groups are particularly at risk?

Answer 26

Indian | Sub-Saharan Africa

Question 27

What is a caseating granuloma?

Answer 27

An organised collection of macrophages, specifically w/ necrosis (common sign in TB)

Question 28

What is commonly associated with granuloma development in TB?

Answer 28

Peripheral lymphocyte infiltration

Question 29

What happens to M. tuberculois bacterium after invasion?

Answer 29

The immune cells trap them in granulomas, and the life cycle is changed

Question 30

What is the life cycle of M. tuberculosis within the human body?

Answer 30

``` Invasion + Colonization Latency Resuscitation Disease Reactivation + Dissemination Transmission ```

Question 31

What is different about milliary tuberculosis?

Answer 31

Early phase is uncontrolled, with wide spread of TB | Diagnosed by millet seed like spots on CXR

Question 32

What is the MoA of Rifampicin?

Answer 32

Inhibits mycobacterial RNA polymerase (Bactericidal)

Question 33

What is Rifampicin used for?

Answer 33

Essential component of short-course regimens: | Rifampicin 450mg o.d. (<50kg) OR 600mg o.d. (>50kg)

Question 34

What are the common side effects of Rifampicin?

Answer 34

``` Hepatitis Rash Fever Flu syndrome Multiple drug interactions ```

Question 35

What is the MoA of Isoniazid?

Answer 35

Inhibits cell wall mycolic acid synthesis | Rapid bactericidal effect on replicating organisms at 300mg o.d.

Question 36

What are the side effects of Isoniazid?

Answer 36

Hepatitis Peripheral neuropathy Cutaneous hypersensitivity

Question 37

What is the MoA of Pyrazinamide?

Answer 37

Entirely unknown Plays a key role in sterilising inflammatory tissue 1.5g o.d. (<50kg) or 2g o.d. (>50kg)

Question 38

What are the side effects of Pyrazinamide?

Answer 38

``` Hepatitis Anorexia Flushing Cutaneous hypersensitivity Hyperuricaemia ```

Question 39

What is the MoA of Ethambutol?

Answer 39

Entirely unknown | Mod. bactericidal, 15mg/kg/day used as an adjunct (1-2 mo)

Question 40

What are the side effects of Ethambutol?

Answer 40

Optic neuritis

Question 41

What is the MoA of Streptomycin?

Answer 41

Binds to mycobacterial ribosome (16S rRNA + S12 protein) inhibiting protein synthesis Bactericidal, 15mg/kg, must be given parenterally

Question 42

What are the side effects of Streptomycin?

Answer 42

Ototoxicity

Question 43

What are the two principles which underlie therapeutic regimens?

Answer 43

Mycobacterium within an infected individual are at different phases of replication Mycobacterial population contains naturally occurring resistance mutants

Question 44

What are the two phases of therapy?

Answer 44

Bactericidal - Majority of organisms are killed | Sterilising - Persisting organisms are eliminated

Question 45

What is the problem with single drug therapy?

Answer 45

Mycobacteria develop chromosomal mutations too fast (1in10^6 - 1in10^8) In a bacillary population large enough single drug therapy ALWAYS selects resistant organisms

Question 46

What is the minimum duration of therapy required for eradication?

Answer 46

Six months

Question 47

What is the standard antituberculous regimen in the UK?

Answer 47

Rifampicin + Isoniazid + Pyrazinamide + Ethambutol for 2 months THEN Rifampicin + Isoniazid for 4 months Otherwise patient is RIPE for infection

Question 48

What are DOT programmes?

Answer 48

DOT programmes use a nurse/surrogate to directly observe all doses being taken

Question 49

What is the most common pattern of drug resistant TB?

Answer 49

Isolated Isoniazid resistance (4-6%)

Question 50

What is the second most common pattern of drug resistant TB?

Answer 50

Rifampicin resistance (2%)

Question 51

What factors suggest MDR TB?

Answer 51

Previous TB treatment Known contact with a case of MDR TB Infection in a country/group with high prevalence of MDR TB Failure to respond to conventional treatment Co-existing HIV infection

Question 52

What is the initial management of MDR TB?

Answer 52

>4 drugs to which the organism is likely to be sensitive | Treatment continuing until 3-6 mo AFTER sputum is culture negative

Question 53

What is the long term management of MDR TB?

Answer 53

After initial treatment therapy should be continued with 3> drugs for 15-18 months Surgery may be necessary