Microbiology: Antimicrobial agents Flashcards
What are the main categories of antibiotics?
-Penecillins (Beta-Lactam) -Cephalosporins (Beta-Lactam) -Carbapenems (Beta-Lactam) -Monobactams (Beta-Lactam) -Glycopeptides -Aminoglycosides (Inhibitor of protein synthesis) -Tetracyclines (Inhibitor of protein synthesis) -Macrolides/ Lincosamides/ Streptogramins – The MSL group (Inhibitors of protein synthesis) -Chloramphenicol (Inhibitor of protein synthesis) -Oxazolidinones (Inhibitor of protein synthesis) -Quinolones (Inhibitor of DNA synthesis) -Nitromidazoles (Inhibitor of DNA synthesis) -Rifamycins (Inhibitor of RNA synthesis) -Cell membrane toxins -Sulfonamides (Inhibitors of folate metabolism) -Diaminopyrimidines (Inhibitors of folate metabolism)
Inhibitors of cell wall synthesis: 2 types. What are they?
-Beta-lactams -Glycopeptides
4 examples of Beta-lactam antibiotics?
-Penecillins -Cephalosporins -Carbapenems -Monobactams -//⛢”Ben’s in Luck, because PENny’s Choice of CAR is a MONdeo”
2 examples of Glycopeptide antibiotics?
-Vancomycin -Teicoplanin
Beta lactam mechanism of action?
-Inactivate the enzymes involved in the terminal stages of cell wall synthesis (transpeptidases, aka penicillin binding proteins) -bacteriocidal, against rapidly dividing bacteria -Ineffective against bacteria that lack peptidoglycan cell walls (e.g. Mycoplasma or Chlamydia)
Beta lactam targets what?
-Transpeptidase
What bacteria does penicillin act on?
-Gram positive organisms, Streptococci, Clostridia. -Not S. Aureus //Broken down by an enzyme (β-lactamase) produced by S. aureus)
What bacteria does amoxacillin act on?
-Broad spectrum penicillin. Gram positive organisms, Streptococci, Clostridia. Extends coverage to Enterococci and Gram negative organisms ; -Not S. Aureus //Broken down by an enzyme (β-lactamase) produced by S. aureus)
What bacteria does flucloxacillin act on?
-Similar to penicillin although less active. -So Gram positive organisms, Streptococci, Clostridia. -Stable to β-lactamase produced by S. aureus.
What bacteria does piperacillin act on?
-(Similar to amoxicillin) -Broad spectrum penicillin Gram positive organisms, Streptococci, Clostridia. Extends coverage to Enterococci and Gram negative organisms ; -extends coverage to Pseudomonas and other non-enteric Gram negatives; broken down by β-lactamase produced by S. aureus and many Gram negative organisms. So not effective on S. Aureus and many Gram negative organisms
What bacteria do clavulanic acid and tazobactam act on?
-S. Aureus, Gram negatives and anaerobes -β-lactamase inhibitors. Protects penicillins from enzymatic breakdown and increases coverage.
How do bacteria develop resistance to Beta lactams?
-By producing Beta-Lactamase enzymes
3 Types of cephalosporins?
-1st, 2nd and 3rd generation
Cephalosporins: 4 types?
-Cephalexin: 1st generation -Cefuroxime: 2nd generation -Cefotaxime: 3rd generation -Ceftriaxone: 3rd generation
Glycopeptides target what bacteria?
-Only gram positive organisms
5 types of inhibitors of Protein Synthesis?
-Aminoglycosides (e.g. gentamicin, amikacin,tobramycin) -Tetracyclines -Macrolides (e.g. erythromycin) / Lincosamides (clindamycin) / Streptogramins (Synercid) – The MSL group -Chloramphenicol -Oxazolidinones (e.g. Linezolid)
Aminoglycosides: Mechanism?
-Inhibitor of protein synthesis -Aminoglycosides bind to the amino-acyl site of the 30s ribosomal unit -Rapid, bacteriocidal action
What types of bacteria do aminoglycosides have no activity on?
Anaerobes
Most significant side effect of aminoglycosides?
-Nephrotoxicity (Reduced kidney function)
Aminoglycosides work synergistically with what type of antibiotic?
-Beta Lactams
What bacteria do tetracyclines act on?
-Broad spectrum activity on intracellular pathogens
In what cases should tetracyclines not be given?
-Pregnancy and children
An example of an antibiotic that can cause a light sensitive rash as a side effect?
Tetracycline
Tetracycline mechanism of action?
-Inhibitor of protein synthesis -Reversibly binds to 30S ribosomal subunit -Bacteriostatic
What bacteria do macrolides act on?
-Minimal gram -ve activity
Macrolide mechanism of action?
-Inhibitor of protein synthesis -Binds to 50s ribosomal unit
-In what cases are macrolide antibiotics particularly useful?
-For use in penicillin-allergic patients
In the case of penicillin-allergic patients, what antibiotic do you use?
-Macrolides
What antibiotic is associated with grey baby syndrome?
-Chloramphenicol
Chloramphenicol mechanism of action?
- Inhibitor of protein synthesis
- Chloramphenicol binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation
Oxazolidinone mechanism of action?
-Inhibitor of protein synthesis -Binds to 23S component of 50s ribosomal unit.
What bacteria do oxazolidinones act on?
-Highly active against Gram positive organisms, including MRSA and VRE. Not active against most Gram negatives.
Types of inhibitors of DNA synthesis?
-Quinolones (eg ciprofloxacin) -Nitromidazoles (eg metronidazole)
An example of a quinolone?
-Ciprofloxacin
An example of a nitromidazole?
-Metronidazole
Fluoroquinolone mechanism of action?
-Inhibitor of DNA synthesis -Act on alpha-subunit of DNA gyrase
Ciprofloxacin, Levofloxacin and Moxifloxacin are all examples of what antibiotic?
-Fluroquinolones (aka quinolones)
Ciprofloxacin, Levofloxacin and Moxifloxacin are all examples of what antibiotic?
-Fluoroquinolones (aka quinolones)
What are fluoroquinolones used to treat?
-UTIs, pneumonia, atypical pneumonia & bacterial gastroenteritis
Nitromidazole mechanism of action?
-Inhibitor of DNA synthesis -Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
Metronidazole & Tinidazole are examples of what antibiotic?
-Nitromidazoles
Types of inhibitors of RNA synthesis?
-Rifamycins (Only one)
An example of a rifamycin?
-Rifampicin
Mechanism of action of rifampicin?
-Inhibitor of RNA synthesis -Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation
What extra precaution needs to be taken when giving rifampicin?
-Monitor LFTs (Due to hepatotoxicity) -Beware of other drugs metabolised by the liver (eg OCP) -Combine with other drugs to prevent resistance developing, which can occur easily through a point mutation causing a change in shape of RNA polymerase.
Antibiotics that act as cell membrane toxins?
-Daptomycin -Colistin
Types of inhibitors of folate metabolism
-Sulfonamides -Diaminopyrimidines (eg trimethoprim)
An example of a sulfonamide?
-Sulfamethoxazole
An example of a diaminopyrimidine?
-Trimethoprim
Mechanism of action of Sulfonamides?
-Inhibition of folate metabolism, therefore impairing DNA synthesis
Mechanism of action of Diaminopyrimidines?
-Inhibition of folate metabolism, therefore impairing DNA synthesis
Sulphonamides work synergistically with what antibiotic class?
-Diaminopyrimidines
Outline the mechanisms of antimicrobial resistance please
-Chemical modification or inactivation of the antibiotic -Modification or replacement of target -Reduced antibiotic accumulation (Impaired uptake or enhanced efflux) -Bypass antibiotic sensitive step
Give an example of inactivation as a mechanism of antibiotic resistance
-Beta lactamase enzyme produced to break down beta lactam antibiotics -Can occur in Staphylococcus aureus (//not MRSA) and Gram Negative Bacilli (Coliforms).
Give an example of altered targets as a mechanism of antibiotic resistance
-MRSA encodes an altered penicillin binding protein (PBP) which has a low affinity for beta-lactams -Comes from mecA gene -MRSA is able to function as normal, in high concentrations of Beta-lactams -(extra) Macrolides, 23S rRNA subunit changes conformation, reducing macrolide binding.
