1 - Introduction to antibacterial agents Flashcards
Antibiotics
Chemical products of microbes that inhibit or kill other organisms
Antimicrobial agents
Antibact/fungal/viral
Antibiotics
Synthetic compound with similar effect
Semi-synthetic i.e. modified from antibiotics
Bacteriastatic Definition
Inhibit bacterial growth - protein synthesis inhibitors
Bactericidal Definition
Kill bacteria - cell wall-active agents
Minimum inhibitory concentration
Minimum concentration of antibiotic at which visible growth is inhibited
Synergism
Activity of two microbials given together is greater than the sum of their activity if given separately
Antagonism
One agent diminishes the activity of another
Indifference
Activity unaffected by another agent
Example of synergism in clinical practice
B-lactam/aminoglycoside combintaion therapy of streptococcal endocarditis
Targets of antibiotics
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
Bacterial cell wall contains…
Peptidoglycan
Describe peptidoglycan
Major component of cell wall
Both gram-+ve and gram–ve
Polymer of glucose derivatives, N-acetyl muramic acid (NAM) & N-acetyl glucosamine (NAG)
No cell wall in animal cells = selective toxicity
What is selective toxicity
Destroy bacterial cells and not human cells
Cell wall synthesis inhibitors
B-lactams
Glycopeptides
Cycloserine (anti-tuberculous agent)
B-lactam antibiotics what are they?
First true antibiotics = penicillins
All contain B-lactam ring three carbons in a ring with nitrogen.
B-lactam antibiotics how do they work
interfere with function of penicillin binding proteins, which are transpeptidases enzymes involved in the petideoglycan cross-linking
Penicillin vs enterobacteriaceae
Ampicillin
Anti-staphyolococcal penicillin
Meticillin
Penicillin main examples
Amoxicillin - relatively narrow spectrum
Cephalosporins example
Cefuroxime - broad spectrum
Carbapenems examples
Meropenem, imipenem
Extremely broad spectrum
Monobactams
Aztreonam - gram-ive activity only
Glycopeptides
Vancomycin, teicoplanin
Large molecules bind directly to terminal D-alanyl-D-alanine on NAM pentapeptides.
Inhibits transpeptidase binding.
Gram-positive activity only as cannot penetrate gram–ve outer membrane
Aminoglycosides
Gentamicin, amikacin
Bind to 30S ribosomal unit (small)
Do not understand mechanism
Can cause nephrotoxicity so careful when dealing with people with AKI
Protein synthesis inhibitors
Macrolides, lincosamides, streptogramins
e.g. erythromycin, clarithromycin (macro)
clindamycin (linco) bind to 50S ribosomal subunit, block tunnel exit, inhibit protein elongation
Tetracyclines
Tetracycline, doxytetracycline
Bind to 30S ribosomal unit and inhibit RNA translation
Oxazolidinones
Linezolid
Inhibit initiation of protein synthesis binds to 50S
Trimethoprim and sulfonamides
Inhibit folate synthesis, which is purine synthesis precursor.
Trimethoprim e.g. dihydrofolate reductase
Sulfonamides e.g. dihydropteroate synthetase
Combined as co-trimoxazole
Quinolones and fluoroquinolones
Inhibit one or more of two related enzymes
e.g. nalidixic acid, ciprofloxacin, levofloxacin
Rifampicin
RNA poly inhibitor
Prevents mRNA synthesis
Plasma membrane agents
Colistin (gram–ve) - last resort antibiotic - but resistance even goes this far recently.
Daptomycin (gram-+ve) cyclic lipopeptides destroy cell membrane
Adverse effects of all drugs
Nausea etc
Infusion reactions
Allergic reactions
Generation of antibiotic resistant - adverse effects
Selection of resistant strains in patient
Preferential colonisation on exposure to resistant stains
Fungal infection adverse effects
Superficial and invasive candidasis
Another adverse effect of antibiotics
C. diff
Aminoglycosides adverse effects
Reversible renal impairment on accumulation
Irreversible ototoxicity
Need drug monitoring via blood tests to check for accumulation
B-lactams adverse effects
1-10% general rash
0.01% anaphylaxis
Linezolid adverse effects
Bone marrow depression
B-lactams and allergy
Intolerance (nausea, diarrhoea etc)
Minor allergic reactions (non-severe skin rash)
Severe allergic reactions (anaphylaxis, urticaria, angio-oedema, bronchospasm, severe skin reaction (Stevens-Johnson syndrome)
Which drugs are safe to use in people with penicillin allergies?
Cephalosporins, Carbapenems in patients with non-severe penicillin allergy
Aztreonam in patients with any penicillin allergy
Common precipitating antibiotics for C.diff
4Cs: Co-amoxiclav Cephalosporins Ciprofloxacin Clindamycin
Less common precipitating antibiotics for C.diff
Benzylpenicillin, aminoglycosides, glycopeptides.
Piperacillin-tazobactam
Could be any antibiotics however
Key antibiotic/bacteria combo
Flucloxacillin
Staph aureus (not MRSA)
Key antibiotic/bacteria combo
Benzylpenicillin
Strep pyogenes
Key antibiotic/bacteria combo
Cephalosporins
(avoid in elderly)
Gram–ve bacilli
Key antibiotic/bacteria combo
Metronidazole
Anaerobes
Key antibiotic/bacteria combo
Vancomycin
Gram-positives (MRSA)
Key antibiotic/bacteria combo
Meropenem
Most clinically-relevant bacteria
Key antibiotic/bacteria combo
Colistin
Last option for multi-resistant gram–ves
in vivo efficacy for CSF as site of action
B-lactams = good
Aminoglycosides + vancomycin = poor
In vivo efficacy for urine as site of action
B-lactins = good
Trimethoprim = good
MLS antibiotics = poor
Main determinant of bacterial killing is:
the factor by which concentration exceeds the MIC = minimal inhibitory concentration
Which drugs are administered intermittently to achieve high peaks?
Aminoglycosides
Which drugs are administered frequently to maintain a high level?
B-lactams
What effects pharmacodynamic concentrations
Concentration and time dependent
Combination therapy benefits
Increase efficacy
Provides adequately broad spectrum
Reduce resistance
