Antibiotics Flashcards
Why are antimicrobials so important?
Before anti-microbials, 90% of children with bacterial meningitis died. Strep throat was at times fatal, and ear infections sometimes spread to the brain. A third of patients with pneumonia died.
What is meant by selective toxicity?
Compounds harm pathogen not host.
What was the first effective antisyphilitic discovered in 1909?
“Salvarsan”
Arsenic containing
When was penicillin discovered and by who?
1928
Fleming
When was prontosil discovered?
1932
Domagk
Define antimicrobial.
Any substance active against microbes
Define antibiotic.
A 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
Bacteriostatic vs Bactericidal - depends on..? (2)
– Microorganism (bacterial inoculum)
– antibiotic concentration
When is bactericidal preferred? (2)
When inadequate penetration to infection site e.g. endocarditis, meningitis, osteomyelitis
If immune system is compromised e.g. neutropenia, renal failure, diabetes
Give examples of bacteriostatic antibiotics. (6)
Chloramphenicol Clindamycin Erythromycin Tetracyclines Trimethoprim Sulfonamides
Give examples of bacteriocidal antibiotics. (6)
Aminoglycosides Beta lactams Vancomycin Quinolones Rifampin Metronidazole
Describe a synergistic antimicrobial combination.
Give an example.
Their combined activity is greater than the sum of the individual activities – e.g B-lactam and aminoglycoside
Describe a antagonistic antimicrobial combination.
Give two examples.
The activity of one drug is compromised by the other – e.g Tetracycline or Chloramphenicol associated with B-lactam or aminoglycoside, or 2 B-lactams together
Describe the Therapeutic Index curve.
Antimicrobial conc over time - begins sub-therapeutic, then goes to therapeutic, and if rises too high = toxic. Then reduces back down into sub-therapeutic. The therapeutic range is between sub-therapeutic and toxic.
What is the therapeutic index?
Therapeutic Index = Toxic / Therapeutic
Give an example of an antimicrobial with a high therapeutic index.
Beta lactams
Give an example of an antimicrobial with a low therapeutic index.
Aminoglycosides
Beta lactams - bacteriostatic or bacteriocidal? How do they work? What other class works in the same way?
Bactericidal
Aim against cell wall synthesis. They make a hole in the bacterial wall and cells die as they can’t maintain osmosis.
Glycopeptides
How do quinolones work?
Works against DNA gyrase
How does metronidazole work?
Stops DNA replication
Which antimicrobial works on DNA-directed RNA polymerase?
Rifampicin
Which antimicrobials work on protein synthesis? (5)
50S inhibitors - chloramphenicol, macrolide, clindamycin
30S inhibitors - aminoglycosides, tetracyclines
Which antimicrobials work on folic acid metabolism? (2)
Trimethoprim
Sulfonamides
Are most hospital infections gram positive or negative? Why is this an issue?
Negative
Most antimicrobials are for gram positive
Give some examples of anti-Gram-positive antimicrobials.
Penicillins Fusidic acid Macrolides Clindamycin Glycopeptides Oxazolidinones Daptomycin
Effective C diff antimicrobial
Glycopeptides e.g. vancomycin
Give some examples of anti-Gram-negative antimicrobials.
Polymyxin (Colistin) Trimethoprim Aminoglycosides Monobactams (Aztreonam) Temocillin
Give some examples of broad spectrum antimicrobials.
Beta lactams - Carbapenems, Amoxicillin/clavulanate, Piperacillin/tazobactam, Cephalosporins
Chloramphenicol
Tetracycline
Why is Chloramphenicol not used a lot anymore?
Due to adverse reactions
Which two antimicrobials classes act on peptidoglycan/bacterial cell wall synthesis?
Beta-lactam
Glycopeptides
Penicillins used in Barts Trust include..?
Penicillin V (oral)
Benzylpenicillin (iv)
Flucloxacillin (oral and iv)
Amoxicillin +/– clavulanic acid (a beta-lactamase inhibitor) (oral and iv)
Piperacillin + tazobactam (a beta-lactamase inhibitor)
Penicillin - mechanism of action and spectrum?
Route of administration?
Inhibit cell wall synthesis
Gram +
Oral and IV
• Side-effects: rule out penicillin allergy immediate IgE mediated
anaphylaxis (0.05%); safe in pregnancy and in children, Jarisch
Herxheimer reaction, Coombs positive haemoytic anaemia,
interstitial nephritis, serum sickness, hepatitis, drug fever
Why does penicillin need to be given 4-6 times a day?
Rapidly excreted
Penicillin - penetration? Side effects? Interactions?
penetrates most tissues including inflamed meninges
side effects - rule out penicillin allergy immediate IgE mediated anaphylaxis (0.05%); safe in pregnancy and in children, Jarisch Herxheimer reaction, Coombs positive haemoytic anaemia, interstitial nephritis, serum sickness, hepatitis, drug fever
Interactions: Allopurinol, methotrexate
Penicillin - resistance and mechanism of resistance?
> 80% of staphylococci resistant; S. pneumoniae resistance in USA, S. Europe; gonococcal resistance worldwide
Mechanism: production of B-lactamase and alteration of PBPs
Penicillin - clinical uses?
drug of choice streptococcal and meningococcal disease e.g. meningitis, pneumonia and respiratory infections, syphilis,
Amoxicillin mechanism of action.
inhibit cell wall synthesis
Amoxicillin dosing regimen.
Three times a day
Amoxicillin penetration.
penetrates most tissues including inflamed meninges
Side-effects of amoxicillin.
rule out penicillin allergy; safe in pregnancy and in children. AAD*, fever, neutropenia, eosinophilia, rash with monucleosis, increased PT, Kounis syndrome
Clinical uses of amoxicillin.
drug of choice for streptococcal disease except when
used empirically for a sore throat; listeria
Mechanism of penicillin.
bactericidal, inhibits transpeptidation of cell wall
Interactions of amoxicillin.
Allopurinol (rash)
