Antibacterial Agents Flashcards
Define antibiotic
Chemical products of microbes that inhibit/kill other organisms
Define Antimicrobial agents
- Antibacterial, antiviral, antifungal
- Antibiotics
- Synthetic/semi-synthetic compounds with similar effects
What are the different types of bacterial killing?
- Bacteristatic= inhibit bacterial growth (protein synthesis inhibitors)
- Bactericidal= kill bacteria (cell-wall active agents)
What is the minimum inhibitory concentration?
Minimum conc of antibiotic at which visible growth is inhibited
-Some antibiotics are bacteriostatic at low conc and bactericidal at high conc
What types of antimicrobial interactions are there?
- Synergism (activity of 2 antimicrobials given together is greater than the sum of their activity separately)- B-lactam/aminoglycoside combination for strep endocarditis
- Antagonism (one agent diminishes activity of another)
- Indifference (activity unaffected by addition of another agent)
Name some cell wall synthesis inhibitors
- B-lactams
- Glycopeptides
- Cycloserine (antiTB agent)
Describe the structure of a bacterial cell wall
- Peptidoglycan major component in gram +ve & -ve bacteria
- Polymer of glucose-derivatives NAG & NAM
How do B-lactam antibiotics work?
Interfere with function of penicillin binding proteins- Transpeptidase enzymes involved in the peptidoglycan cross-linking
Describe the general structure of B-lactams
- Four membered B-lactam ring structure (C-C-C-N)
- Structural analogue of D-alanyl-D-alanine
Name the groups of B-lactam antibiotics, members of each family and their spectrum
- Penicillins (benzylpenicillin, amoxicillin, flucloxacillin- narrow spectrum)
- Cephalosporins (Cefuroxime, ceftasidime- broad spectrum)
- Carbapenems (meropenem, imipenem-extremely broad spectrum)
- Monobactams (aztreonam- gram -ve activity only)
Name types of glycopeptides and how they work
- Vancomycin, teicoplanin
- Bind directly to terminal D-Alanyl-D-alanine on NAM pentapeptides
- Inhibit binding of transpeptidases thus peptidoglycan cross-linking
- Unable to penetrate gram -ve outer membrane porins
How are proteins synthesised in bacteria?
- Translation of RNA to a protein
- Takes place in ribosome
- 50S + 30S= 70S
Give examples of Aminoglycosides, where they bind and what they are known for?
- Gentamicin, amikacin
- Protein synthesis inhibitors
- Bind to 30S ribosomal subunit
Give examples of MLS, what it stands for, where they bind and what they are known for?
- Macrolides, Lincosamides, Streptogramins
- Protein synthesis inhibitors
- M= erythromycin, clarithromycin
- L= clindamycin
- Bind to 50S ribosomal subunit= blockage of exit tunnel or inhibit protein elongation
Where do tetracyclines bind to, what are they known for?
- Protein synthesis inhibitors
- Bind to 30S ribosomal subunit
- Inhibit RNA translocation= interfere with binding of tRNA to rRNA
Give an example of an Oxazolidinone, where it binds and what it is known for?
-Protein synthesis inhibitor
-Linezolid
-Binds to 50S ribosomal subunit- may also bind to 70S subunit
-Inhibits initiation of protein synthesis
-Inhibit assembly of initiation complex
-
What are Trimethoprim & Sulphonamides inhibitors of and how? What is their combined name?
- DNA synthesis
- Inhibit folate synthesis (folic acid= purine synthesis precursor)
- T=Dihydrofolate reductase
- S=Dihydropteroate synthase
- Combined= Co-Trimoxazole
Give examples of Quinolones & fluoroquinolones, what they inhibit and how?
- Ciprofloxacin, Nalidixic acid
- Inhibit 1 or more of 2 related enzymes- DNA gyrase & topoisomerase IV
- Involved in remodelling of DNA during DNA replication
What is Rifampicin and how does it do this?
- RNA synthesis inhibitor
- RNA polymerase inhibitor
- Prevents synthesis of mRNA
Name some plasma membrane agents
- Colistin (gram -ve)
- Daptomycin (gram +ve)
- Destruction of cell membrane
What are adverse effects of antibiotics?
- C.Diff
- Antibiotic resistance
- Fungal infection (candidiasis)
- Nausea/vomiting, rashes
What are the adverse reactions of aminoglycosides?
- Reversible renal impairment on accumulation
- Irreversible ototoxicity
- Therapeutic drug monitoring indicated
What are the adverse reactions of B-lactams?
Allergic reactions: Generalised rash or anaphylaxis
What are the adverse reactions of Linezolid?
Bone marrow depression
What are signs of intolerance or allergy to B-lactams?
I= nausea, diarrhoea, headache A= skin rash, anaphylaxis, urticaria, angio-oedema, severe skin rash, bronchospasm
Describe C.Diff infection
- Combination of enterotoxin & spore production
- Hypervirulent strain 027 causes more severe disease
- Produces toxins A & B
- Assumed caused by abolition of colonisation resistance
What are the most common precipitating antibiotics of C.Diff?
- Co-amoxiclav
- Cephalosporins
- Ciprofloxacin
- Clindamycin
What are the best antibiotics to use against:
- Staph Aureus
- Strep Pyogenes
- Gram -ve Bacilli
- Anaerobes
- MRSA/gram +ve
- last option for gram -ves
- SA=Flucloxacillin
- SP=Benzylpenicillin
- GB=Cephalosporins- avoid in elderly
- A=Metronidazole
- MRSA= Vancomycin
- Last= Colistin
Which antibiotics have a good and poor availability in the CSF?
Good= B-lactams in presence of inflammation Poor= Aminoglycosides & Vancomycin
Which antibiotics have a good and poor availability in urine?
Good= Trimethoprim & B-lactams Poor= MLS antibiotics
What are concentration dependent pharmacodynamics?
Main determinant of bacterial killing is the factor by which concentration exceeds MIC, administered intermittently
What are time dependent pharmacodynamics?
Main determinant of killing is the amount of time for which antibiotic concentration exceeds MIC, administered frequently to maintain high levels
Why is combination therapy used?
- Reduce resistance
- Provide adequately broad spectrum
- Increase efficacy
