Antibiotics Flashcards
What is selective toxicity?
Where compounds harm the pathogen but not the host
Define antimicrobial
Any substance active against microbes
Define antibiotic
Naturally occurring product active against bacteria
Define broad spectrum
Kills most germs gram positive and negative or anaerobes
Define narrow spectrum
Kills narrow range of microbes
Define bactericidal
Actively kills bacteria
Define bacteriostatic
Prevents bacteria multiplying
What does an antibiotic’s role of being bactericidal or bacteriostatic depend on?
- microorganism number (if lots of bacteria less likely to be bactericidal)
- antibiotic concentration (if low may not be sufficient to kill so not cidal)
- is immune system compromised as affects antibiotic efficacy
- infection site penetration capability
Bactericidal agent examples
Penicillin
Beta lactams
Aminoglycosides
Bacteriostatic agent examples
Tetracyclines
Chloramphenicol
Azithromycin
What are synergistic antibiotics?
Combined activity is greater than sum of individual activities
Example of synergistic antibiotics
Beta lactams
Aminoglycoside
antagonistic antibiotics define
Activity of 1 drug is compromised by other
Example of antagonistic antibiotics
Tetracycline and chloramphenicol with beta lactam or aminoglycoside
2 beta lactams together (penicillin and flucloxacillin in staph)
What is the significance of a therapeutic index?
Narrower index means more likely to be toxic
= toxic/therapeutic
Example of an antibiotic with a high therapeutic index
Beta lactam
Example of an antibiotic with a low therapeutic index
Aminoglycosides
What do beta lactams and glycopeptides do?
Inhibit cell wall synthesis
What do quinolones do?
Inhibit DNA gyrase
What does trimethoprim and sulfonamides do?
Inhibit folic acid metabolism
What do polymixins do?
Destroy cytoplasmic membrane structure
What does rifampicin do?
Inhibits DNA directed RNA polymerase
What do macrolides, clindamycin and chloramphenicol do?
Inhibit protein synthesis
50S inhibitors
What do aminoglycosides and tetracyclines do?
Inhibit protein synthesis
30S inhibitors
Examples of antibiotics against gram positive bacteria
Penicillins against strep, staph, listeria Fusidic acid Macrolides against strep Clindamycin - strep Glycopeptides against strep and staph Oxazolidinones - strep and staph Daptomycin - strep and staph
Examples of antibiotics against gram negative bacteria?
Polymixin Trimethoprim Aminoglycosides - also against strep and staph which are gram positive Monobactams Temocillin
Examples of broad spectrum antibiotics
Beta Lactams (Carbapenems Amoxicillin Piperacillin Cephalosporins)
Chloramphenicol - also positive, negative, anaerobes
Tetracycline - also positives, negative, anaerobes
What is the bacterial cell wall like?
- peptidoglycan
- not contained in eukaryote cell wall
What do penicillins do? Use, dose, admin, side effects
- inhibit cell wall synthesis
- gram positive
- oral and IV
- 4-6 times a day dose
- penetrate most tissues inc. meninges
- side effect allergy IgE mediated anaphylaxis,
- pregnancy safe
- for streptococcal and meningococcal disease
- produces beta lactamase and alters protein binding protein to bacteria
- resistance to many staphylococcus and S. penumoniae, worldwide gonococcal
- rash with allopurinol
Amoxicillin
- inhibits cell wall synth
- gram positive and negative
- oral and IV
- 3 x a day
- penetrates most
- penicillin allergy, fever, neutropenia, mononucleosis
- pregnancy safe
- resistance staphylococci and pneumoniae, worldwide gonococcal
- for streptococcal drug choice if not sore throat, listeria
- produces beta lactamase and PBP
- rash with allopurinol
Flucloxacillin
- inhibits cell wall synth
- gram positive
- oral and IV
- 4 x a day
- penetrates most
- penicillin allergy, rash, leukopenia
- pregnancy
- same resistance as pen
- S. aureus drug of choice except MRSA
- alters PBP
Co-amoiclav
- amoxicillin and clavulanic acid
- inhibits cell wall synth and beta lactamase inhibitor
- gram +, -, anaerobes
- oral and IV
- 3 x a day
- penetrates most
- liver injury
- MRSA resistance to it
- for polymicrobial infections
- alters PBP, impermeability, efflux
Piptazobactam
- piperacillin and tazobactam
- inhibits cell wall and beta lactamase inhibitor
- gram +, -, anaerobes
- IV
- 3-4 x day
- penetrates most
- pen allergy, neutropenia, hypernatremia
- MRSA resistant
- for polymicrobial inf.
- PBPs, efflux, impermeability
- interacts with methotrexate
Cefuroxime
- cell wall
- +, -, pseudomonas
- IV
- 3 x day
- penetrates most
- allergy, C. difficile
- pregnancy and children
- MRSA res.
- for pneumonia, intra ab serious and UTIs
- PBP, efflux, impermeability, beta lactamases
Ceftriaxone
- cell wall \+, -, not pseudomonas - IV - 1/2 a day - penetrates most and inflamed meninges - allergy, C. difficile - MRSA resistant - for meningitis and pneumonia - PBPs, efflux, imp.
Ceftazidime
- cell wall
- and -, pseudomonas
- IV
3 x day - penetrates most and inflamed meninges
- allergy, C. difficile
- MRSA resistant
- for UTIs, inta ab, not for community acquired infection
- PBPs, efflux, beta lactamase, impermeability
Carbapenems
- cell wall, beta lactamase inhibits
- +, -, anaerobes, pseudomonas
- IV
- 3 x day
- penetrates most inc. inflamed mininges
- allergy, rash, seizures
- MRSA resistant
- for polymicrobial inf.
- PBP, efflux, imp
Glycopeptides - vancomycin
- cell wall
- +, anaerobes
- IV
- 1/2 x day
- poor penetration into CSF
- nephrotoxic
- VRE resistant
- for problem gram positive infections
- alters binding site
Which agents inhibit protein synthesis?
Aminoglycosides Tetracyclines Chloramphenicol Macrolides (erythromycin, clarithromycin) Clindamycin Fusidic acid
Aminoglycosides - gentamicin, amikacin
- acts on 30S ribosome
- gram +, -, pseudomonas
- IV
- 1 a day
- water soluble, poor lung and CNS penetration
- nephrotoxicity and ototoxicity
- gram - org resistant some
- use for serious systemic sepsis
- efflux, imp
- nephrotoic with vancomycin, colistin
Macrolides - erythromycin, azithromycin, clrithromycin
- acts on 50S ribosome
- bacteriostatic
- gram +
- oral and IV
- 1/2 x day
- excellent IC penetration
- children
- QT prolong, inhibits P450, otitis media, pharyngitis, legionnairs
- staph and strep resistance
- for atypical agents, pen allergy and STIs
- mutates binding site
Which drugs affect nucleic acid metabolism
- quinolones
- rifampicin
-metronidazole
(nucleic metabolism similar in bacteria to mammals so selective toxicity is often poor except with these)
Quinolones
- inhibits DNA gyrase
- +, staph not strep, -, pseudomonal
- oral and IV
- 2 x a day
- meninges and most penetrate
- not pregnant
- lowers seizure threshold, tendon rupture
- high resistance rates
- UTI, intra abdom,
- not for pneumonia
- efflux and imperm
Examples of antifolates
Sulphonamides (inhibits dihydropteroate synthase)
Trimethoprim (inhibits dihydrofolate reductase which is in human cells to but is much more active on bacterial enzyme)
Role of dihydrofolate reductase
Dihydrofolate to tetrahydrofolate
- trimethoprim targets
Role of dihydropteroate synthase
Forms dihydropteroate from first molecules
Targeted by sulphonamide
Examples of membrane disorganising agents
Amphotericin (antifungal agent)
Colistin (polymyxin)
Daptomycin
Qualities of an ideal antibiotic
- selectively toxicity
- reach and concentrate target organ
- reach good levels in body fluids infected
- minimally toxic
- does not select resistance
- inexpensive
Antibiotic misuse
Widely prescribed - often when conditions did not require them
- agricultural use (dose cattle to increase yield, battery farming to control infection)
Antimicrobial resistance problems
UTIs RTIs Neisseria gonorrhea M. TB DIarrhoeal disease Penicillin resistance MDR Salmonella H. Influenzae Growing hospital resistant infections (methicillin resistant S. aureus, enterococci) Need in emergency department
