Antibiotics Flashcards
What are antibiotics made from?
β Natural products of fungi and bacteria
β derived from natural products by fermentation
β then modified chemically to increase antimicrobial effects
Why are other bacteria and fungi used as a source of antibiotics?
β Natural antagonism and selective advantage
β It allows the organism to live in the soil without other organisms killing them
What is an example of a synthetic antibiotic?
β Sulphonamides
How did Fleming discover penicillin?
β He left an agar plate on the windowsill for too long
β mold lysed all S. Aureus colonies
What is selective toxicity due to?
β Differences in structure and metabolic pathways between the host and the pathogen
What is the aim of selective toxicity?
β target the microbe not the host
Why is selective toxicity difficult to achieve?
β There is variation between microbes
β viruses, fungi and parasites are intracellular
What is the active dose like for toxic drugs?
β Narrow
What does the dose need to be?
β high enough to kill the pathogen but low enough to not cause harm to the body
What is it called if the difference between the effective dose and the toxic dose is small?
β Narrow therapeutic margin
What is the minimum inhibitory concentration?
β concentration at which the drug needs to be effective
If someone is on vancomycin why do you have to do blood tests?
β to make sure that the levels of antibiotics have not reached toxic levels
What type of toxicity do aminoglycosides and vancomycin have?
β ototoxicity and nephrotoxicity
What is microbial antagonism?
β one organism producing something that inhibits the growth of another due to competition between flora
What does loss of flora lead to?
β Bacterial or pathogen overgrowth
How can antibiotics cause C.diff?
β lots of people have C.diff as a commensal in their gut and if they take antibiotics C. diff can outgrow the flora
What is pseudomembranous colitis?
β swelling or inflammation of the colon due to overgrowth of C.diff
What antibiotics cause antibiotic associated colitis?
β Clindamycin
β Broad spectrum lactams
β Fluoroquinolones
Why is it difficult to decontaminate a C.diff infection?
β The spores are volatile and get everywhere
What does antibiotic + immunity lead to?
β bacterial clearance
What modifications do you have to do to an antibiotic course to people who are imunosuppressed?
β more toxic antibiotics
β combinations of antibiotics
What are the three ways antibiotics are classified by?
β Type of activity
β Structure
β Target site for activity
What do bactericidal antibiotics do and when are they used?
β Kill bacteria
β used when the host defense mechanisms are impaired
β required in endocarditis, kidney infection
What do bacteriostatic antibiotics do and when are they used?
β Inhibit bacteria
β used when the host defense mechanisms are intact
β used in many infectious diseases
What is the concentration like comparing bactericidal vs bacteriostatic?
β bacteriostatic is usually lower
What is an example of a bacteriostatic antibiotic?
β Tetracycline
What is an example of a broad spectrum antibiotic and what are they effective against?
β Cefotaxime
β Effective against many types
What is an example of a narrow spectrum antibiotic and what are they effective against?
β Penicillin G
β effective against very few types
What are first generation cephalosporins effective for?
β effective for gram + but not gram -
What do you need to do to drugs to make them effective against gram - bacteria?
β chemically modify them
What are second generation cephalosporins effective for?
β they were modified to be more effective against gram - but as a result their gram + effectiveness was also reduced
What are third generation cephalosporins useless against?
β S. aureus
What type of antibiotics are beta lactams?
β structural mimics of natural substrates for enzymes
What antibiotics have beta lactam rings?
β penicillins
β cephalosporins
What can bacteria have that makes beta lactams ineffective?
β beta lactamases which degrade the beta lactam structure
Which two antibiotic inhibit folic acid metabolism?
β Trimethoprim
β Sulfonamide
Why is inhibiting folic acid effective?
β Humans donβt have folic acid enzymes
Which two antibiotics inhibit the cell membrane synthesis?
β Colistin (cyclic polypeptide)
β Daptomycin (lipopeptide)
Which 7 antibiotics inhibit cell wall synthesis?
β Cycloserine β Vancomycin, Teichoplanin β Bacitracin β penicillins β Cephalosporins β Monobactams β carbapenems
Which 3 antibiotics inhibit 50S ribosome subunit and hence protein synthesis?
β Erythromycin
β Chloramphenicol
β Clindamycin
Which 8 antibiotics inhibit the 30S ribosome subunits and hence protein synthesis?
β Tetracycline β Spectinomycin β Streptomycin β Gentamycin, Tobramycin β Amikacin β Tigecycline β Doxycycline
Which antibiotic inhibits DNA and RNA processing?
β Quinolones
How do antibiotics interfere with DNA and RNA processing?
β inhibit DNA Gyrase
β inhibit DNA directed RNA polymerase
How does Rifampicin work?
β Inhibits bacterial RNA polymerase
What is the function of DNA gyrase?
β uncoiling DNA during replication
What are anaerobic bacteria treated with?
β Metronidazole
Why is colistin given even though it is toxic?
β they are effective against UTIs
What is the structure of a gram positive cell wall?
β lipid bilayer plasma membrane with integral proteins
β peptidoglycan cell wall
β lipoteichoic acids traversing the cell wall and are anchored in the cell membrane
What is the structure of a gram negative cell wall?
β lipid bilayer plasma membrane with integral proteins
β periplasmic space
β outer membranes with porins
How do antibiotics work on gram positive bacteria?
β they target the enzymes that make peptidoglycan
β the enzymes are on the outer side of the lipid bilayer
How do antibiotics penetrate gram positive bacteria?
β they can penetrate the porous structure
Why canβt you use antibiotics on gram negative bacteria?
β the outer membrane is impermeable
β the only way things can cross through is through porins
What are peptidoglycans made from?
β cross linked pentapeptides
Why does a beta lactam that inhibits S aureus not work on E.coli?
β The peptidoglycan structure is different
Describe how bacterial cell walls get synthesized?
βThe synthesis starts off by a precursor monomer of a disaccharide with 5 peptides
βThe last 2 peptides in the monomer are alanines (isomers specific to bacteria D-ala)
βAfter this the precursor is linked to a lipid transport molecule which transports it across the membrane
β5 cross linked amino acids are added to the peptide chain
βIt is polymerised in the cell wall by enzymes
βThe enzyme recognises the terminal D-ala and cleaves it off, it then attaches it to the next pentapeptide
βThe cross linking is done by enzymes called trans and carboxypeptidases
βThey are only found in bacterial cell walls
How do antibiotics interfere with the production of the bacterial cell wall?
βblock the production of D-ala (cycloserine)
β prevent the transport of the D-ala across the membrane
βBeta lactams inhibit enzymes that do the crosslinking
How does vancomycin work to inhibit the production of the bacterial cell wall?
βVancomycin is not a beta lactam but it affects peptidoglycan synthesis by recognising the D-ala terminal and binds to it
βThis means the carboxypeptidases canβt act on the D-ala substrate because the vancomycin is attached to it
What do beta lactams act as?
β substrate mimics and competitive inhibitors for the trans and carboxypeptidases
What happens if you destroy the beta lactam ring?
β It breaks up the structure and is not a competitive inhibitor
What does the periplasmic space in gram negative bacteria contain?
β peptidoglycan structure
What are PBP?
β penicillin binding proteins
What kind of response do bacteria have if they cannot produce peptidoglycan?
β Autolytic response
Why can some bacteria not be treated with beta lactams?
β Not all bacteria have peptidoglycan cell walls
What is an example of bacteria that beta lactams do not work on?
β mycoplasma pneumoniae
How do cell walls get made in gram negative bacterial cell wall?
βPBP (penicillin binding proteins) are cross linking proteins in the cytoplasmic membrane
βThe precursors are made and they are added to the pentapeptide by the PBP then transferred to the periplasmic space
What do sulfonamides inhibit and how?
β dihydropteroate synthetase which is unique to bacteria
β the sulfonamide structure is almost identical to PABA and competes against it
How is tetrahydrofolic acid synthesized?
Dihydropteroate diphosphate + p-aminobenzoic acid (PABA) enz : (dihydropteroate synthase)
β
dihydropteroic acid
β
tetrahydrofolic acid enz : (dihydrofolate reductase)
Why does trimethoprim not act on host enzymes?
β It has very low affinity for the host enzyme but high affinity for the bacterial enzyme
How does streptomycin work?
β binds to the 30S ribosome
β preventing binding of fmet t-RNA to the A site
β preventing initiation complex formation
How does gentamicin work?
β preventing translocation of fmet tRNA to P site
How does tetracyline work?
β competition with new aminoacyl t-RNA at the A site
How does chloramphenicol work?
β Blocks formation of peptide bond peptidyl transferase
β binds to 50S subunit
How does erythromycin and fusidic acid work?
β blocks translocation of peptidyl t-RNA
What are the 7 reasons that antibiotics are used?
β Treatment of bacterial infections β prophylaxis β decreased carriage rates β prevention of infections β peri-operative cover for gut surgery β people with higher susceptibility to infection β inappropriate use
What are the 3 methods of administration for antibiotics?
β IV
β topical
β oral
Why would you give IV antibiotics?
β Vomiting, unconscious, poor gut absorption due to trauma
β unable to take oral
Why would you give topical antibiotics?
β Conjunctivitis β superficial skin infections β burns β antiseptic creams β heavy metal ointments
What does the dose of antibiotic depend on?
β age β weight β renal and liver function β severity of the infection β susceptibility of the organism β properties of the antibiotic
In what 5 situations do you give antibiotic combinations?
β before an organism identified in life-threatening conditions
β polymicrobial infections
β less toxic doses of an individual drug possible
β synergy
β reduce antibiotic resistance
What are two life threatening conditions where an antibiotic combination has to be taken?
β endocarditis
β septicaemia
What are 2 examples of polymicrobial infections?
β Abscess
β GI perforation
What are 4 examples of cephalosporins?
β Cefalexin
β Cefuroxime
β Cefotaxime
β Ceftazidime
What is Cefalexin used to treat?
β An oral agent primarily used to treat UTIs
What is Cefuroxime used for?
β Parenteral 2nd generation agent with good activity against many gram + and gram - organisms
What is Cefotaxime used for?
β A parenteral 3rd generation agent with greater activity against many gram - and retaining gram + activity
What is Ceftazidime used for?
β A parenteral 3rd generation agent with a spectrum of activity extended to include pseudomonas aeruginosa
What are the 3 aminoglycosides?
β Gentamicin
β Amikacin
β Streptomycin
How must aminoglycosides be given and why?
β they cannot be absorbed from the gut and must be given parenterally
What are aminoglycosides active against?
β Predominantly against gram - bacteria including pseudomonas aeruginosa
Why must serum levels be monitored with aminoglycosides?
β these agents are nephrotoxic and ototoxic
What is an example of a macrolide?
β Erythromycin
What is erythromycin used to treat?
β gram + infections
β especially in those allergic to beta lactams
β mycoplasma pneumoniae and legionella pneumophilia
What are 2 examples of glycopeptides?
β Vancomycin and teicoplanin
What are glycopeptides used to treat?
β Active against only gram +
How should glycopeptides be given and when?
β For use when other agents cannot be used e.g MRSA
β Parenteral only
What are 2 examples of tetracyclines?
β Oxytetracycline
β Doxycycline
What kind of spectrum are tetracyclines?
β broad
What are tetracyclines used to treat?
β Chlamydia
β acne
β mycoplasma pneumoniae
What are two examples of quinolones?
β Ciprofloxacin
β Moxifloxacin
What are quinolones used for?
β complicated UTIs and GI infections
β respiratory tract infections
What is trimethoprim used for?
β UTIs
What is trimethoprim combined with?
β Sulfamethoxazole as co-trimoxazole
What is metronidazole effective against?
β anaerobic bacteria (and some parasites)
What spectrum is chloramphenicol?
β broad
What is chloramphenicol used for?
β topically for eye infections
Why is chloramphenicol not used systemically?
β because of side-effects
What kind of spectrum is fusidic acid?
β narrow
What is fusidic acid used to treat?
β staphylococcal infections only
What is nitrofurantoin useful for?
β UTIs
What type of drug is linezolid?
β Oxazolidinone
What is linezolid used for?
β Multi resistant gram + infections only
What kind of a drug is daptomycin and what is its spectrum like?
β lipopetide
β similar to vancomycin
What is tigecycline used for?
β used against multiply resistant gram + and -
