Antibiotics 1 Flashcards
- What are three targets for antibiotics?
Peptidoglycan layer of cell wall
Inhibition of bacterial protein synthesis
DNA gyrase and other prokaryote-specific enzymes
- Name two groups of antibiotics that inhibit cell wall synthesis.
Beta-lactams
Glycopeptides
- What are the three groups of beta-lactam antibiotics?
Penicillins
Cephalosporins
Carbapenems
- Give two examples of glycopeptides.
Vancomycin
Tiecoplanin
- What is the difference between Gram-positive and Gram-negative bacteria?
Gram-positives has a thick peptidoglycan cell wall
Gram-negatives have an outer membrane with a thin peptidoglycan cell wall
- Outline the mechanism of action of beta-lactam antibiotics.
Inactivate enzymes that are involved in the terminal stages of cell wall synthesis Inhibits transpeptidases (aka penicillin-binding protein) This means that there are no peptide crosslinks between peptidoglycan chains so the cell wall is weak Beta-lactam is a structural analogue of the enzyme substrate
- During which phase of the cell cycle will beta-lactams be ineffective?
Stationary phase
The cells need to be rapidly dividing
- Which type of bacteria are beta-lactams ineffective against?
Bacteria with no cell wall (e.g. Mycoplasma and Chlamydia)
- List four types of penicillin.
Penicillin
Amoxicillin
Flucloxacillin
Piperacillin
- For each of the following antibiotics, describe their coverage and mechanisms of resistance:
Penicillin
Amoxicillin
Flucloxacillin
Piperacillin
a. Penicillin
Active against Gram-positives (e.g. Streptococci, Clostridia)
Broken down by beta-lactamases (mainly produced by S. aureus)
NOTE: penicillin is the MOST ACTIVE beta-lactam antibiotic
b. Amoxicillin
Broad-spectrum penicillin
Extends coverage to Enterococci and Gram-negative organisms
Broken down by beta-lactamase produced by S. aureus and many Gram-negatives
c. Flucloxacillin
Similar to penicillin but less active
Does NOT get broken down by beta-lactamase produced by S. aureus
d. Piperacillin
Similar to amoxicillin
Extends coverage to Pseudomonas and other non-enteric Gram-negative organisms
Broken down by beta-lactamase produced by S. aureus and many Gram-negatives
- Name two beta-lactamase inhibitors. What is the benefit of giving beta-lactamase inhibitors with beta-lactams?
Clavulanic acid
Tazobactam
Protect penicillins from breakdown by beta-lactamases thereby increasing the coverage to include S. aureus, Gram-negatives and anaerobes
- List examples of 1st, 2nd and 3rd generation cephalosporins.
1st = cephalexin
2nd = cefuroxime
3rd = ceftriaxone, ceftazidime, cefotaxime
NOTE: as you go up the generations you get increasing activity against Gram-negatives and less activity against Gram-positives
- What is the benefit of cephalosporins over penicillins?
They are not broken down by beta-lactamases
- What is a disadvantageous association of ceftriaxone?
Associated with C. difficile infection
- What is a benefit of ceftazidime?
Good anti-Pseudomonas cover
- List three examples of carbapenems.
Meropenem
Imipenem
Ertapenem
- List examples of bacteria that have shown carbapenem resistance.
Acinetobacter
Klebsiella
- Which type of bacteria are glycopeptides effective against and why?
Gram-positives
They are large molecules so they cannot cross the outer membrane of Gram-negative cell walls
- What is a major side-effect of glycopeptides?
Nephrotoxic
Monitor blood levels to prevent accumulation
- Outline the mechanism of action of glycopeptides.
Glycopeptides bind to amino acid chains at the end of peptidoglycan precursors and prevent glycosidic bonds being formed (via transglycosidase) and prevent peptide crosslinks being formed (via transpeptidase)
NOTE: they are similar to beta-lactams but instead of binding to the enzymes, they bind to substrates (cell wall component precursors)
- List some classes of antibiotics that work by inhibiting protein synthesis.
Aminoglycosides Tetracyclines Macrolides Lincosamides (e.g. clindamycin) Streptogramins (e.g. Synercid) Chloramphenicol Oxazolidinones (e.g. linezolid)
- Outline the mechanism of action of aminoglycosides.
Binds to amino-acyl site of the 30S ribosomal subunit and prevents elongation of the polypeptide chain
It also causes misreading of the codons along the mRNA
- What are some major side-effects of aminoglycosides?
Ototoxic and nephrotoxic
- Which aminoglycosides are particularly active against Pseudomonas aeruginosa?
Gentamicin
Tobramycin
- What is a major issue with tetracyclines?
Widespread resistance (most Gram-negatives)
- Which groups of patients should not receive tetracyclines?
Children and pregnant women
Because it can deposit in bone and cause discoloration of growing teeth
- Outline the mechanism of action of tetracyclines.
Binds to the ribosomal 30S subunit and prevents the binding of aminoacyl-tRNA to the ribosomal acceptor site, thereby inhibiting protein synthesis
- Outline the mechanism of action of macrolides.
Binds to the 50S ribosomal subunit and interferes with translation
Also stimulates the dissociation of peptidyl-tRNA
- What are two major risks of taking chloramphenicol?
Aplastic anaemia
Grey baby syndrome – neonates have reduced ability to metabolise the drug
- Outline the mechanism of action of chloramphenicol.
Binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation
- Outline the mechanism of action of oxazolidinones.
Binds to the 23S components of the 50S subunit to prevent the formation of a functional 70S initiation complex (needed for translation)
- Which organisms are oxazolidinones active against?
Gram-positives (including MRSA and VRE)
Not active against Gram-negatives
- List two groups of antibiotics that inhibit DNA synthesis.
Quinolones
Nitroimidazoles
- List 3 examples of quinolones.
Ciprofloxacin
Moxifloxacin
Levofloxacin
- List 2 examples of nitroimidazoles.
Metronidazole
Tinidazole
- Outline the mechanism of action of quinolones.
Acts on the alpha-subunit of DNA gyrase predominantly with other actions
broad spectrum especially against gram -ve and intracellular organisms
- Outline the mechanism of action of nitroimidazoles.
Under anaerobic conditions, an active intermediate is formed, which causes DNA strand breakage
- Outline the mechanism of action of rifampicin.
Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
- Name two cell membrane toxins.
Daptomycin
Colistin
- Describe the activity of daptomycin.
Gram-positives
Likely to be used in treating MRSA and VRE
- Describe the activity of colistin.
Active against Gram-negatives including Pseudomonas aeruginosa, Acinetobacter baumanii and Klebsiella pneumoniae
NOTE: it is a polymyxin
- Name two families of antibiotics that work by inhibiting folate metabolism.
Sulphonamides
Diaminopyrimidines
- What is co-trimoxazole?
Sulphamethoxazole + trimethoprim
- List some mechanisms of antibiotic resistance.
Chemical modification or inactivation of the drug
Modification or replacement of the target
Reduced antibiotic accumulation (impaired uptake or enhanced efflux)
Bypass antibiotic-sensitive step in cell division
- Which bacteria produce beta-lactamases?
S. aureus and Gram-negative bacilli (coliforms)
NOTE: this is not the mechanism of resistance in pneumococcus and MRSA
- In which groups of bacteria is penicillin resistance not reported in?
Group A, B, C and G beta-haemolytic streptococci
- Describe how MRSA uses ‘altered targets’ as a mechanism of resistance.
MRSA has a mecA gene which encodes novel PBP2a
This has a low affinity for binding beta-lactams therefore is not inactivated by beta-lactams
- Describe the mechanism of resistance in Streptococcus pyogenes.
Results from acquisition of a series of stepwise mutations in PBP genes
Lower level resistance can be overcome by increasing the dose
- Describe the mechanism of resistance to macrolides.
Adenine-N6 methyltransferase modifies the 23S RNA
This reduces the binding of macrolides thereby resulting in resistance
Encoded by erm (erythromycin ribosome methylation) genes
NOTE: caution when using clindamycin in Staphylococcus and Streptococcus which is resistant to macrolides because lincosamides can induce this mechanism of resistance
