Infectious Diseases Flashcards
Erythromycin/ Clindamycin site of action?
50s subunit of ribosome, protein synthesis inhibitors
Linezolid side effects
Myelosuppression, peripheral neuropathy, seretonin syndromes
Rare: optic neuropathy
Aminoglycoside / tetracycline site of action
30s subunit of ribosome, protein synthesis inhibitors
Linezolid site of action
Both 50s and 30s subunit of ribosome, protein synthesis inhibitors
Method of action of beta lactams, vancomycin
Cell wall synthesis
Daptomycin method of action
Loss of cell wall selective permeability
Note: binds to surfactant & cannot be used in lung infections
Quinolone method of action (ciprofloxacin etc)
Inhibits gyrase, unwinding enzyme in DNA replication
Rifampicin method of action
Inhibit RNA polymerase in DNA transcription
Method of action of sulfamethoxazole, trimethoprim
Inhibits folate synthesis
Which antibiotic’s efficacy is determined by peak concentration?
Fluroquinolones, aminoglycosides (ciprofloxacin, gentamicin etc)
Which antibiotic’s efficacy determined by time above MIC?
Beta-lactams
Method of MRSA resistance?
Alteration of penicillin binding protein
MecA Gene encodes for PBP2a
Resistance to all penicillins / cephalosporins / carbapenems
What gene predominated in community acquired MRSA?
Panton-valentine leucocidin (PVL)
Daptomycin side effects
Rhabdomyolysid, eosinophilic pneumonia
Remember: double lung bad!
What gene confers vancomycin resistance?
Amino acid substitution: D-ala D-ala to D-ala D-lac
Prevents vancomycin binding to cross links
Van A gene - vancomycin and teicoplanin resistance
Van B/C gene - vancomycin only
What is the mechanism of S. pneumonia resistance to macrolides?
MefA gene - effluent pump (low resistance)
EmB gene - alteration of binding site (high resistance)
List ESCHAPPM organisms
Enterobacter Serratia Citrobacter freundii Hafnia Aeromonas Proteus Providencia Morganella
—> rapidly inducible production of beta-lactamase
Mechanism of beta-lactam antibiotics?
Bind & acylate active site of penicillin binding protein (PBP) the enzyme essential for the biosynthesis of bacteria cell wall
Mechanism of beta-lactamase?
Is an enzyme that can hydrolyze beta-lactam ring, thus deactivating beta-lactam antibiotics (i.e. resistance mechanism)
Entry of HIV into host cell occurs via which protein?
gp120
R5 strain of HIV
Most frequently transmitted
Less aggressive
Infects macrophages and T cells
Use CXR5 for CD4 cell entry
HIV-2
Less virulent Lower viral load Lower rates of vertical transmission Slower progression Less virulent Seen mainly in Western Africa and western India
Strongest single predictive marker of disease progression at all stages of HIV?
CD38 expression by CD8 cells
HAART: entry inhibitors
Prevent HIV-1 from entering and infecting immune cells
Not widely used
e.g. Maraviroc - CCR5 inhibitor
HAART: Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
Active phosphorylation NRTI metabolites inhibit viral reverse transcriptase and viral DNA synthesis, preventing HIV replication
Nucleoside Analogues
Zidovudine (AE: lipodystrophy, anaemia, myopathy, black nails)
Didanosine (AE: pancreatitis, peripheral neuropathy)
Lamivudine (AE: pancreatitis)
Abacavir (AE: increased CVD, hypersensitivity reaction - rash, fever, GI symptoms; HLA-B*5701 allel)
Nucleotide Analogues
Tenofovir (AE: renal impairment, osteoporosis)
HAART: Protease Inhibitors
Inhibit HIV proteases, preventing viral mutation and replication
Examples: Indinavir, Atazanavir, Saquinavir
AE: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition, lipodystrophy
Indinavir and Atazanavir: renal stones, hyperbilirubinaemia
All PIs need to be combined with Ritonavir for its pharmacological boosting effect
HAART: absolute contraindications to Protease Inhibitors
Cisapride - torsades
Lovastatin - rhabdo (use pravastatin instead)
Midazolam - prolonged sedation
HAART: Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Reversibly inhibit HIV reverse transcriptase, reducing viral DNA synthesis
Nevirapine (AE: rash, hepatitis)
Efavirenz (AE: psychiatric adverse effects; contraindicated in first trimester of pregnancy)
Effect of being heterozygous for CCR5 Delta 32 allel in the development of HIV and AIDS?
Slower disease progression to AIDS
HAART: integrase strand transfer inhibitors
Inhibits HIV integrase, which prevents viral replication by stopping insertion of viral DNA into the host DNA
Raltegravir
Dolutegravir
HIV and HBV Co-infection
Leads to
- milder necroinflammatory activity
- higher rate of chronic infection
- lower rate of HBeAg seroconversion
- more commonly HBeAg positive
- higher DNA levels
- faster progression to cirrhosis
First line treatment of toxoplasma encephalitis in a patient with HIV?
Pyrimethamine-sulphadiazine
At what CD4 count is CMV disease usually seen?
CD4 < 50
Needle stick injury - risk of transmission
Hep B - 30%
Hep C - 3%
HIV - 0.3%
Moxifloxacin covers which organisms
Streptococcus pneumonia
Staphylococcus aureus
Mycoplasma pneumonia’s
Serratia aeruginosa
Only oral agent for pseudomonas cover?
Ciprofloxacin
