Antibiotics Flashcards
What is the difference between bacteriostatic and bactericidal?
Bateristatic - inhibit bacterial growth
eg. Protein synthesis inhibitors
Bactericidal - kill bacteria
eg. Cell wall-active agents
Give an example of antimicrobial synergism?
β-lactam/aminoglycoside combination therapy of streptococcal endocarditis
What are the 5 antibiotic targets?
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
Which antimicrobial agents are cell wall synthesis inhibitors?
β-lactams
Glycopeptides
What do the β-lactam antibiotics have in common and give some examples
All contain β-lactam ring:
Four-membered ring structure (C-C-C-N)
Structural analogue of D-alanyl-D-alanine
They Interfere with function of “penicillin binding proteins”
Transpeptidases enzymes involved in the peptideoglycan cross-linking
eg. Penicillin’s, Cephalosporin’s, Carbapenems, Monobactams
What do Glycopeptides have in common and give some examples
Large molecules, bind directly to terminal D-Alanyl-D-Alanine on NAM pentapeptides
Inhibit binding of transpeptidases and thus peptideoglycan cross-linking
Gram-positive activity
Unable to penetrate Gram-negative outer membrane porins
eg. Vancomycin, teicoplanin
What are the antimicrobial agents which inhibit protein synthesis?
Aminoglycosides - eg. Gentamicin
Macrolides - eg. Erythromycin
Lincosamides - eg. Clindamycin
Streptogramins
Tetracyclines - eg. Doxytetracycline
Oxazolidinones - eg. Linezolid
What is the specific mechanism of the Aminoglycosides? with examples
Aminoglycosides bind to the 30S ribosomal subunit
Aminoglycosides - eg. Gentamicin, amikacin
What is the specific mechanism of the Macrolides, Lincosamides and Streptogramins? with examples
Macrolides, Lincosamides and Streptogramins bind to 50S ribosomal subunit
Blockage of exit tunnel inhibits protein elongation
Macrolides - eg. Erythromycin, clarithromycin
Lincosamides - eg Clindamycin
What is the specific mechanism of the Tetracyclines? with examples
Tetracyclines bind to 30S ribosomal subunit.
Inhibit RNA translation by interfering with binding of tRNA to rRNA
eg. tetracycline, doxytetracycline
What is the specific mechanism of the Oxazolidinones? with examples
Oxazolidinones bind to 50S ribosomal subunit
They prevent the assembly of initiation complex
eg. Linezolid
What are the antimicrobial agents that inhibit DNA synthesis?
Trimethoprim and Sulfonamides
eg. combined = co-trimoxazole
Quinolones and fluoroquinolones
eg. Nalidixic acid, ciprofloxacin, levofloxacin
What is the specific mechanism of Trimethoprim and Sulfonamides?
They inhibit folate synthesis
Folic acid is a purine synthesis precursor
Trimethoprim inhibits dihydrofolate reductase
Sulfonamides inhibit dihydropteroate synthetase
What antimicrobial is an RNA synthesis inhibitor and what is its mechanism?
Rifampicin
RNA polymerase inhibitor
Prevents synthesis of mRNA
Which antimicrobials attack the plasma membrane?
Colistin (Gram-negatives)
Daptomycin (Gram-positives)
Cyclic lipopeptides which cause destruction of cell membranes
What are the antibiotic-specific adverse effects of aminoglycosides?
Reversible renal impairment on accumulation
Irreversible ototoxicity (toxic to cochlear nerve)
Therapeutic drug monitoring indicated
What are the antibiotic-specific adverse effects of β-lactams?
Allergic reactions:
Generalised rash 1-10%
Anaphylaxis approx. 0.01%
What are the antibiotic-specific adverse effects of Linezolid?
Bone marrow depression
Which antibiotics are the most common for precipitating a C. difficile infection
4Cs Co-amoxiclav (amoxicilin-clavulanate) Cephalosporins Ciprofloxacin Clindamycin
What are the 6 methods a bacteria can use to become resistant to antibiotics?
No target – no effect Reduced permeability – drug can’t get in Altered target – no effect Over-expression of target – effect diluted Enzymatic degradation – drug destroyed Efflux pump – drug expelled
Why is vancomycin ineffective against gram-ve bacilli?
Gram-negatives have an outer membrane that is impermeable to vancomycin
Why is Gentamicin ineffective against anaerobic organism?
Uptake of aminoglycosides requires an O2 dependent active transport mechanism
How has MRSA developed resistance to flucloxacillin?
Altered penicillin-binding protein (PBP2’, encoded by MecA gene) does not bind β-lactams
How has VRE (vancomycin resistant enterococci) developed resistance?
Altered peptide sequence in Gram-positive peptideoglycan, reduces binding of vancomycin 1000 fold
How have some gram-ve bacilli become resistant to Trimethoprim?
Mutations in the dihydrofolate reductase gene
Give two examples of bacteria using enzyme degradation to become resistant to antibiotics
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) are resistant to penicillin’s and cephalosporin’s
Aminoglycoside-modifying enzymes provide resistance against Gentamicin
What is horizontal transfer?
Antibiotic resistance gene is put into a plasmid
Plasmid transferred between organisms by conjugation
What is the treatment for strep pyogenes infection?
Benzylpenicillin
Which antibiotic is used to treat MRSA?
Vancomycin
What is the specific mechanism of the quinolones and fluoroquinalones? with examples
Inhibit one or more of two related enzymes:
DNA gyrase and topoisomerase II
Involved in remodelling of DNA during DNA replication
What is in co-amixoclav and why?
Amoxicillin - a β-lactam antibiotic, and
clavulanic acid - a β-lactamase inhibitor
Improves the efficacy of amoxicillin against β-lactam resistant bacteria
