L08 - Treatment of Respiratory Infections (inc. TB) Flashcards
Define CAP
Community Acquired Pneumonia
Give four examples of groups in which CAP is more common
Males
The elderly
Alcoholics
Chronic disease sufferers
What proportion of CAP do conventional bacteria cause?
60-80%
What proportion of CAP do ‘atypical’ bacteria cause?
10-20%
What proportion of CAP do viruses cause?
10-20%
What two conventional bacteria are frequently implicated in CAP?
S. pneumoniae
H. influenzae
What three ‘atypical’ bacteria are frequently implemented in CAP?
M. pneumoniae
C. pneumoniae
L. pneumophila
What four microbiological investigations are most commonly used in diagnosis of CAP?
Sputum analysis/culture
Immunofluorescence on sputum samples
Blood cultures
Urinary pneuomococcal/legionella antigen
What three factors is antimicrobial management for CAP based on?
Assessment of likely pathogen
Severity
Likelihood of drug resistance
What is CURB65?
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
What is the treatment regimen for a low severity CAP score (0-1)?
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
What is the treatment regimen for a moderate severity CAP score (2)?
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
If patients are allergic to penicillin what antibiotics can be prescribed instead? - CAP Score <2
Mild - i.v. Cefuroxime 1.5g t.d. (+ i.v. Clarithromycin 500mg b.d.)
Severe - Ciprofloxacin 400mg b.d. + Vancomycin
What is the treatment regimen for a severe CAP score (3)?
Co-amoxiclav 1.2g t.d. + Clarithromycin 500mg b.d. for 10 days
If patients are allergic to penicillin what antibiotics can be prescribed? - CAP Score >3
Levofloxacin 500mg b.d. + Vancomycin 1g b.d. for 10 days
If MRSA is likely what antibiotics should be prescribed?
Levofloxacin 500mg b.d. + Vancomycin 1g b.d. for 10 days
In what cases should the time course of the treatment be extended?
Infection with: Legionella Staphylococcal Gram-ve Pneumonia Extend to 14-21 days
When should Mycoplasma infection be suspected?
Young patient
Long prodrome
Pactchy consolidation (CXR)
Extra-pulmonary disease
How should Mycoplasma infection be treated?
Tetracyclines for >14 days
When is CAP caused by S. aureus more likely?
During an influenza outbreak
How should CAP caused by S. aureus be treated?
Flucloxacillin 2g i.v. q.d. ADDED to standard regimen
When should Legionellosis be suspected?
Severe CAP (outbreak)
Multi-lobe involvement (CXR)
Hyponatraemia
Focal neurological disease
How should Legionellosis be treated?
High dose macrolide (up to 4mg Erythromycin per day) + Rifampicin 600mg b.d.
What bacterium causes TB?
M. tuberculosis
What proportion of the world is infected with M. tuberculosis?
1/3
What racial groups are particularly at risk?
Indian
Sub-Saharan Africa
What is a caseating granuloma?
An organised collection of macrophages, specifically w/ necrosis (common sign in TB)
What is commonly associated with granuloma development in TB?
Peripheral lymphocyte infiltration
What happens to M. tuberculois bacterium after invasion?
The immune cells trap them in granulomas, and the life cycle is changed
What is the life cycle of M. tuberculosis within the human body?
Invasion + Colonization Latency Resuscitation Disease Reactivation + Dissemination Transmission
What is different about milliary tuberculosis?
Early phase is uncontrolled, with wide spread of TB
Diagnosed by millet seed like spots on CXR
What is the MoA of Rifampicin?
Inhibits mycobacterial RNA polymerase (Bactericidal)
What is Rifampicin used for?
Essential component of short-course regimens:
Rifampicin 450mg o.d. (<50kg) OR 600mg o.d. (>50kg)
What are the common side effects of Rifampicin?
Hepatitis Rash Fever Flu syndrome Multiple drug interactions
What is the MoA of Isoniazid?
Inhibits cell wall mycolic acid synthesis
Rapid bactericidal effect on replicating organisms at 300mg o.d.
What are the side effects of Isoniazid?
Hepatitis
Peripheral neuropathy
Cutaneous hypersensitivity
What is the MoA of Pyrazinamide?
Entirely unknown
Plays a key role in sterilising inflammatory tissue
1.5g o.d. (<50kg) or 2g o.d. (>50kg)
What are the side effects of Pyrazinamide?
Hepatitis Anorexia Flushing Cutaneous hypersensitivity Hyperuricaemia
What is the MoA of Ethambutol?
Entirely unknown
Mod. bactericidal, 15mg/kg/day used as an adjunct (1-2 mo)
What are the side effects of Ethambutol?
Optic neuritis
What is the MoA of Streptomycin?
Binds to mycobacterial ribosome (16S rRNA + S12 protein) inhibiting protein synthesis
Bactericidal, 15mg/kg, must be given parenterally
What are the side effects of Streptomycin?
Ototoxicity
What are the two principles which underlie therapeutic regimens?
Mycobacterium within an infected individual are at different phases of replication
Mycobacterial population contains naturally occurring resistance mutants
What are the two phases of therapy?
Bactericidal - Majority of organisms are killed
Sterilising - Persisting organisms are eliminated
What is the problem with single drug therapy?
Mycobacteria develop chromosomal mutations too fast (1in10^6 - 1in10^8)
In a bacillary population large enough single drug therapy ALWAYS selects resistant organisms
What is the minimum duration of therapy required for eradication?
Six months
What is the standard antituberculous regimen in the UK?
Rifampicin + Isoniazid + Pyrazinamide + Ethambutol for 2 months THEN
Rifampicin + Isoniazid for 4 months
Otherwise patient is RIPE for infection
What are DOT programmes?
DOT programmes use a nurse/surrogate to directly observe all doses being taken
What is the most common pattern of drug resistant TB?
Isolated Isoniazid resistance (4-6%)
What is the second most common pattern of drug resistant TB?
Rifampicin resistance (2%)
What factors suggest MDR TB?
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
What is the initial management of MDR TB?
> 4 drugs to which the organism is likely to be sensitive
Treatment continuing until 3-6 mo AFTER sputum is culture negative
What is the long term management of MDR TB?
After initial treatment therapy should be continued with 3> drugs for 15-18 months
Surgery may be necessary
