Anti-microbial drugs Flashcards
Criteria to characterise antibiotics
effect on bacteria:
- kill bacteria – bactericidal
- inhibit/arrest growth of bacteria – bacteriostatic
range of bacterial species affected:
- a large number of bacterial species - broad spectrum
- a limited number of bacterial species - narrow spectrum
- a single species – limited spectrum
Targets of antibiotics
interfere with/inhibit essential cellular structures/processes
target bacteria-specific structures/processes
such modes of action make them
- toxic to bacteria only
- innocuous to humans (little or no-side effects)
Essential cellular structures and processes in bacteria
cell wall, plasma membrane, protein synthesis
Antibiotics that act on Peptidoglycan biopsynthesis
Penicillin, Cephalosporin, Carbapenem, Vancomycin
B-lactam antibiotics
are effective against growing and dividing cells
kill bacteria by autolysis (bactericidal)
resistant bacterial species produce B-lactamase, a secreted enzyme which inactivates antibiotics by breaking down their B-lactam ring
Penicillin - natural (penicillin G) and aminopenicillin (amoxicillin, ampicillin)
Cephalosporins
Carbapenems
Penicillins
very effective against grame positive bacteria
some allergic reactions
aminopenicillins better tolerated
Cephalosporins
different primary coverage: 1st = grame positive bacteria 2nd = anaerobes 3rd = gram negative bacteria 4th - pseudomonas
Meticillin
resistant to B-lactamase
replaced by more stable and similar penicillins:
Oxacillin, Flucloxacillin, Dicloxocillin
Vancomycin
glyco-peptide antibiotic = more allergic reactions
an inhbitor of CW biosynthesis:
- different more of action to B-lactams, different chemical structure
effective against MRSA
- administered i.v
Antibioitcs inhibiting protein synthesis
some bind to and inhibit protein components of the 30S sub unit:
eg. Tetracycline, Doxycycline
Aminoglycosides (Gentamycin, Streptomycin, Tobramycin)
others bind to, and inhibit protein components of the 50S sub-unit:
eg. Macrolides (Erythromycin, Clarithromycin), Chloramphenicol
- broad spectrum, effective against both gram negative and positive species
- most are bacteriostatic
- associated with greater toxicity
Antiobiotics inhibiting DNA synthesis
Fluoroquinolones eg. Cirprofloxacin, Levofloxacin
- broad spectrum, synthetic
- inhibit bacterial enzymes with essential roles in DNA replication
- effective against gram negative bacteria and intra-cellular pathogens (legionella, mycoplasma)
- associated with high levels of toxicity
Antibiotics inhibiting RNA bio-synthesis
RNA bio-synthesis requires DNA-dependent RNA polymerases
eg. Rifampicin
- inhibits bacterial but not human RNA polymerases
- used to treat TB
Antibiotics inhibiting folate biosynthesis
eg. Sulfonamide
- analogues of PABA, act by substrate competition
Trimethoprim
- inhibits digydrofolate reductase
Co-trimoxazole
- a mixture of both, inhibits both steps of the pathway
Sources of antibiotics
natural, produced by: > fungi - penicillin, cephalosporin > bacteria - erythromycin, rifampicin, streptomycin, tetracycline semi-synthetic : > ampicillin snythetic: > sulfonamides, trimethoprim
Choice of antibiotic treatment depends on…
bacterial species susceptibility to drug site of infection safety of drug cost of therapy patient fcators
Antibiotic resistance
mutations in bacterial chromosomal genes encoding targets of common antibioitics (vertical gene transmission)
transfer between organisms of resistance genes carried by plasmids (horizontal gene transmission)
biofilm formation
