Infection Flashcards
SSTI inflammation process in response to bacterial infection
1) Bacteria and other pathogens enter wound
2) Platelets from blood release blood-clotting proteins at wound site
3) Mast cells secrete factors which increase delivery of blood, plasma and cells to injured area
4) Neutrophils secrete factors that kill and degrade pathogens
5) Phagocytosis by neutrophils and macrophages
6) Macrophages secrete cytokines that attract immune cells to site to activate tissue repair
7) Inflammatory response continues until foreign material eliminated
Role of IL-8 in infection
Pro-inflammatory cytokine release by macrophages that help neutrophils find site of infection
PAMPs
Pathogen-associated molecular patterns found on pathogen surfaces
PRRs
Pattern recognition receptors found on host cell surfaces
LPS PAMPs are found on gram ____ bacteria
Negative
LTA PAMPs are found on gram ____ bacteria
Positive
NfkB
Tissue factor that activates proinflammatory cytokine production
Organisms that cause SSTI
Mainly S. aureus and S. pygogenes
Also some other bacteria, fungi (tinea) and viruses (chickenpox)
Streptococcus identification
Gram positive cocci Catalase negative (as opposed to staph)
Group A streptococcus
S. pyogenes
Presents a “group A” antigen which is recognised by a specific antibody
Show beta haemolysis on blood agar
MSCRAMMs
Microbial surface components recognising adhesive matrix molecules
Large protein family expressed on bacteria e.g., S, pyogenes which specifically bind to host ECM proteins e.g., collagen, elastin, fibronectin
Ways that S. pyogenes can evade an immune response
1) Hyaluronic acid capsule
2) M protein (binds factor H which prevents opsonisation with C3b and therefore resists phagocytosis)
3) Secretion of toxins
4) Spreading factors
4 types of toxins that S. pyogenes secretes
1) streptolysins (which lyse immune cells)
2) C5a peptidase (breaks up C5a to prevent neutrophil chemotaxis)
3) DNases (degrade neutrophil extracellular traps)
4) SpyCEP (destroys IL-8 to prevent neutrophil chemotaxis)
4 types of spreading factors that S. pyogenes secretes
Proteases
Lipases
Hyaluronidase
Streptokinase
Streptokinase
Anticoagulant that activates plasminogen to plasmin which degrades fibrin
Main classes of B-lactam antibiotics
Penicillin
Cephalosporins
Carbapenems
How does penicillin work?
Binds to transpeptidase enzyme which prevents formation of peptide cross-links in bacterial cell wall
Results in weak cell wall and eventually cell lysis
3 types of penicillin
Penicillin G (IV, aqueous, rapid excretion)
Benzathine penicillin G (IM, low concentration, slow excretion)
Penicillin V (oral, absorbed well from GI tract on empty stomach)
Amoxycillin
Septic arthritis
Presence of infection from bacteria in bone/marrow/joint space
Occurs most frequently in childhood
General systemic symptoms including fever and malaise, as well as swelling, erythema, and tenderness around the infected joint
Nonsuppurative GAS disease
Delayed sequelae following uncomplicated infection with GAS
Non-pus-forming
Treatment of septic arthritis
First, bacteria needs to be isolated by aspirating the joint and gram staining/growing/catalase staining
Drainage and washout of the joint required
Intravenous antibiotics needed initially then longer course of oral antibiotics
Major Jones criteria of ARF
Carditis Polyarthritis Sydenhams chorea Erythema marginatum Subcutaneous nodules
Minor Jones criteria of ARF
Fever Polyarthralgia History of rheumatic fever Raised acute phase reactants Prolong PR interval
ARF diagnosis
2 major criteria OR 1 major and 2 minor
PLUS evidence of preceding strep infection either by rising or elevated strep antibody titres OR positive GAS throat culture
How does ARF lead to RHD?
Antibodies cross-react with collagen or cardiac valvular endothelia antigens, then T cells infiltrate leading to inflammation or long-term damage
Recurrent ARF attacks due to repeated strep infection lead to increased scar formation in the valve. After the attack of ARF and carditis, the valve scars and is neurovascularised, perpetuating RHD
Streptococcal titres
antistreptolysin O and antiDNase B titres
Can be elevated even when throat culture is normal
ASO titre level highest about 3–6 weeks after infection, which is about when children will present with ARF
ARF treatment
Bed rest
System inflammation monitoring
Family testing
Penicillin IM injections every 4 weeks for the next 10 years, or until 21, whichever is longer
Main component of bacterial cell wall
Peptidoglycan
Most common causes of pharyngitis
50% S. pyogenes
40% rhinoviruses/other viruses
10% other (e.g., influenza, EBV)
Partial haemolysis
Alpha haemolysis
Green
By viridans streptococci
Complete haemolysis
Beta haemolysis
Completely disappears
S. pyogenes
No haemolysis
Gamma haemolysis
Enterococcus faecalis
Sinusitis aetiology
90%–98% of the time viral
Rest of the time bacterial
Types of LRTI
Pneumonia
Pleurisy
Empyema
Lung abscess
What is the only bacteria that has been shown to cause bronchitis?
Bordatella pertussis
S. penumoniae virulence factors
1) Pneumococcal surface protein A (binds epithelial cells and prevents C3b deposition)
2) PspC (prevents complement activation)
3) Pili (contributes to colonisation and cytokine production)
4) Choline binding protein (binds to Ig receptors on epithelial cells and allows transport into cells)
5) Pneumolysin (lyses neutrophils and epithelial cells)
6) Polysaccharide capsule
Transformation
Bacteria commit suicide and release their DNA
Other individuals take up this DNA nad express it
Primary investigation for pneumonia
CXR
If normal, antibiotics not required
Following pneumonia tests
Nasopharyngeal swab
Sputum culture
Blood culture
Macrolides target
Ribosomal 50S transpeptidation subunit
Chloramphenicol target
Ribosomal 50S peptidyl transferase subunit
Aminoglycosides target
Ribosomal 30S initiation subunit
Tetracyclines target
Ribosomal 30S tRNA binding
Macrolide example
Erythromycin
Broad spectrum bacteriostatic antibiotic active against strep, staph and chlamydia bacteria
Adverse effects of macrolides
Increased peristalsis therefore GI upset
Sudden death due to QT interval prolongation
Drug–drug interactions
Two types of penumonia
Community acquired
Healthcare associated
Determines treatment
Treatment of healthcare-associated pneumonia
Cefuroxime +/- Gentamicin
Treatment for bronchitis
Treatment for cough with NSAIDs or sedating antihistamines
Antibiotics have been shown to potentially reduce cough duration but no other significant improvement
Possible routes of osteomyelitis infection
Trauma e.g., joint replacement
Spread from local area of infection e.g., SSTI
Haematogenous route e.g., bacteraemia
Pathogenesis of osteomyelitis
Bacteria infect bone
Leukocytes infiltrate infected site
Inflammation and pus
Devacularisation, dead bone and abscess
Pathogenesis of chronic osteomyelitis
Bacteria might invade bone cells and evade immune response and drugs
Patients at risk for osteomyelitis
Diabetics with foot ulcers Patients with traumatic infections Patients undergoing root canals SSTI patients Chickpox-infected children
Osteomyelitis pathogens
S. aureus
S. pyogenes
GBS
Diagnosis of osteomyelitis
Radiology
Bone biopsy
Blood sample if associated with bacteraemia
B-lactam resistant penicillins
Methicillin
Flucloxacillin
Augmentin (amoxicillin + clavulanic acid)
Endocarditis
Infection of the endocardium and heart valves leading to leakiness and eventual heart failure
Death by stroke or crashing pulmonary oedema
Endocarditis pathogenesis
Turbulent flow through abnormal valve
Platelets and fibrin attach to damaged valvular epithelium, forming sterile vegetations
Transient bacteraemia arising from mouth, skin, gut, urinary tract etc. seed bacteria onto sterile vegetations
Infected vegetation enlarges and sheds infected emboli
Valve destruction
Outcomes of endocarditis
Impaired valve function leading to heart failure and crashing pulmonary oedema as the lungs rapidly accumulate fluid
Emboli due to broken off vegetations leading to infarcts (more common)
Three types of bacteraemia
True
Contaminant
Transient
Investigations for endocarditis
1) Blood cultures looking for continuous bacteraemia
2) Investigate valvular function (auscultation, echo, look for evidence of emboli in distant arterioles)
Bactericidal antibiotics
Penicillins
Cephalosporins
Gentamicin
Bacteriostatic antibiotics
Macrolides
Tetracyclines
MIC
Minimum inhibitory concentration
Minimum amount of drug that bacteria will be killed by
Main cause of endocarditis
Viridans streptococci
Then S. aureus
Endocarditis treatment
Antibiotics (dependent on organism), IV, high dose, at least 2 weeks (often 4 weeks)
Cure rate 70%–90%
Could use penicillin plus flucloxacillin plus gentamicin to cover all common bases
Why are bactericidal antibiotics necessary for endocarditis?
Neutrophils cannot enter vegetations, therefore just using a bacteriostatic antibiotic will only prolong the infection
Prevention of endocarditis
Reduce risk of bacteraemia in persons known to have abnormal heart valves (e.g., past RHD, congenital abnormalities)
E.g., antibiotic prophylaxis at time of dental work
Luckily, endocarditis is now so rare that this is barely necessary
Endocarditis vs ARF
Splinter haemorrhages = emboli from vegetations
Continuous bacteraemia = infection in vascular tree
Echo may show vegetations
Gastroenteritis
Syndrome of diarrhoea and/or vomiting
Diarrhoea
3+ loose stools in the past 24 hours
Acute diarrhoea
<14 days
Persistent diarrhoea
14–30 days
Chronic diarrhoea
> 30 days
M cells
Specialised capture cells of the immune system present in the gut which capture foreign particles and transport them to dendritic cells
Allows IgA influx to gut
Clostridium difficile
Opportunistic bacteria that causes gastroenteritis when the normal microbiome of the gut is disrupted, e.g., after antibiotic usage
Non-inflammatory diarrhoea
Mucosal disruption affects absorption/secretion
Watery, no blood or pus
What causes non-inflammatory diarrhoea?
Exotoxin ingestion
Enterotoxin-producing organisms
Viruses
Inflammatory diarrhoea
Normally in the large bowel
Acute mucosal inflammation causing bloody/pussy diarrhoea
What are some organisms that cause inflammatory diarrhoea?
Shigella
Campylobacter
Salmonella enterica
Gram -ve motile bacteria Infects the ileum and colon Long and variable incubation period Low infectious dose Typhoidal (headache) vs. non-typhoidal (diarrhoea)
Salmonella treatment
Intrinsically resistant to cephalosporins and aminoglycosides, with resistance spreading to other antibiotics
Generally, if antibiotics can be avoided then they should be
Giardia lamblia
Parasite of small bowel transmitted through the faecal–oral route
Non-invasive, but causes loss of brush border therefore decreased absorption and diffuse villous shortening
Fatty and malabsorptive diarrhoea, but non-inflammatory
Slow onset, good at surviving in cyst form in water reservoirs therefore can be a recurrent source of infection
Metronidazole
Inert drug that requires activation
Inhibits DNA synthesis
No activity against aerobic bacteria because prodrug not activated
Viral gastroenteritis
Most important are rotavirus, norovirus and enteric adenovirus
Infection of enterocyte epithelium with adherence to mucosa and disruption of absorption/secretion
No acute inflammation or mucosal destruction
Shigella
Gram -ve
Very low infectious dose, very pH resistant
Ulceration and inflammation of colon but doesn’t penetrate past lamina propria therefore no bacteraemia
Incubation period 1–4 days but can shed weeks after infection
Campylobacter
Inflammatory colitis of ileum, jejunum and colon
Enters through M cells and spreads, producing a local inflammatory response
Susceptible to gastric acid, slow growing
Normally transmitted via infected food
Antibiotics used in people with high risk of transmission or complications e.g., chefs, HIV patients
Primary peritonitis
Spontaneous
Bacterial spread without GI perforation
Secondary peritonitis
Bacterial spread from GI or urogenital tracts
Nosocomial
Hospital-acquired infection
Pathophysiology of peritonitis
Bacteria enter peritoneum
Local inflammatory response
Greater omentum is a physical barrier and tries to contain the bacteria
Rapid neutrophil deployment and generalised inflammation
What antibiotics could you use for enterococci?
Cephalosporins e.g., amoxicillin
Ceftrioxime + Metronidazole
Amoxicillin + Gentamicin + Metronidazole
Gentamicin adverse effects
Nephrotoxicity
Ototoxicity
Neuromuscular blockade
Gentamicin dose
5 mg/kg lean body weight daily up to 500 mg
3 mg/kg lean body weight daily in renal impairment
