Dunedin-ID Flashcards
What is the mechanism of MRSA?
Modified penicillin-binding protein (altered target site of beta-lactam binding)
mecA gene encodes for PBP2a which has an altered terminal amino acid resulting in hugely reduced affinity for beta-lactam drug binding
Discuss PVL genes regarding community acquired MRSA and hospital-acquired MRSA
Community acquired MRSA- many carry PVL genes
hospital-associated MRSA: PVL expression less common
Define multi-resistant MRSA
Either two or more of the non-beta-lactam antibiotics e.g. erythro/clinda,* co- trim, genta, rifampicin, fusidic, mupirocin, tetracycline, chloramphenicol
Or ciprofloxacin (marker for the EMRSA-15)
What is PVL (Panto-valentine leucocidin)?
a pore-forming necrotising exotoxin that causes leucocyte destruction and tissue necrosis, with marked neutrophil activation and release of pro-inflammatory cytokines
seen in MRSA
Treatment of non-multi-resistant MRSA
Non-severe: cotrimoxazole, clindamycin, erythromycin, doxycycline, rifampicin, fusidic acid, gentamicin
linezolid
Severe: vancomycin, teicoplanin, daptomycin
What is a S/E of linezolid
reversible bone marrow depression with prolonged use
irreversible neuropathy
optic neuropathy
serotonin syndrome
What is the MOA of linezolid?
bacteriostatic, inhibits bacterial proteins synthesis, binds to both 30s and 50s ribosomal subunits
acts against gram +ve
What is the MOA of daptomycin
cyclic lipopeptide bactericidal antibiotic that causes depolarisation of the bacterial cell membrane
ineffective in respiratory tract infections due to inactivation by pulmonary surfactant
What are S/E of daptomycin?
myopathy, peripheral neuropathy, eosinophilic pneumonia
What is the MOA of tigecycline?
protein synthesis inhibitor, binding at the 30s ribosomal subunit
limited in UTIs
active against acinetobacter and stenotrophomonas
NOT active against pseudomonas, proteus, Providencia
not suitable for treatment of ventilator-associated pneumonia or CNS infections
high volume of distribution
How to treat enterococci?
penicillin, amoxicillin/ampicillin or vancomycin
inherently resistant to cephalosporins
What is the difference between E.faecalis and E.Faecium?
E.Faecalis –> more virulent, sensitive to penicillin/amoxicillin
E.Faecium –> less virulent, usually resistant to penicillin/amoxicillin
Vanc resistant
What is the MOA of vancomycin?
Inhibits synthesis of bacterial cell wall by binding to “D- alanyl-D-alanine terminus of the pentapeptide side-chain” preventing cross-linking.
active against gram POSITIVE bacteria, cant penetrate outer lipid membrane of gram negatives
What are S/E of vancomycin
Nephrotoxicity, ototoxicity, “Red Man” syndrome, neutropenia, thrombocytopenia, rash
What is teicoplanin?
glycopeptide antibiotic, similar to vancomycin but longer half life
How do you get vanc resistance?
D-Ala D-Ala –> D-Ala D-Lac
What gene clusters give rise of Vancomycin resistance?
What are VRE Treatment options?
penicillin/amoxicillin/ampicillin
teicoplanin- only for Van B/ Van C
linezolid
daptomycin +/- beta-lactam
tigecycline
ceftaroline
What is the mechanism of pneumococcal resistant to penicillin and cephalosporin?
alteration of penicillin-binding proteins (transpeptidase enzyme)
therefore clavulanic acid (e.g. augmentin) adds nothing
What is IV penicillin MIC break points?
Non-meningeal infections:
- susceptible: <0.06 mg/L
- resistant >2mg/L
Meningeal infection
- susceptible <0.06mg/L
- resistant: >0.06 mg/L
What is the mechanism of macrolide resistance for S.Pneumonia?
Macrolide resistance occurs via either mefA gene (efflux pump, low level resistance) or ermB gene (alteration of binding site, high level resistance)
What is the difference between gram +ve and gram-ve bacteria?
Gram +ve: 2 layer cell wall (thick peptidoglycan layer), cytoplasmic membrane
Gram -ve: three layer cell wall (outer membrane is outer lipid bilayer), cell wall (thin peptidoglycan layer), cytoplasmic membrane
What is the mechanisms of beta-lactam resistance
1) altered porins (only in gram -ve bacteria)
2) beta-lactamases (ampC, EBSL, CRE)
3) prevention of binding
4) efflux pumps
What is the mechanism of resistance for ESCHAPPM organisms?
AmpC Beta-lactamse genes which may be found on bacterial chromosomes or plasmids
resistant to cephalosporins (apart from cefepime)