Flashcards
Treatment and prevention: Bacteria
Cards in this deck (130)
- 1What are the two sources of antibacterial agents?Natural and synthetic
- 2What is an antibiotic?A natural antimicrobial substance produced by a microorganism
- 3Give two example of fungal antibiotics1) Penicillium spp - penicillin
2) Cephalosporium - cephalosporins - 4What are actinomycetes?Soil bacteria
- 5Give an example of an actinomycetes antibiotic?Streptomyces spp
- 6Define antimicrobialAny substance, natural, semi-synthetic (chemically modified natural substance) or synthetic origin that kills or inhibits the growth of microorganisms
- 7What were the first antimicrobials to be synthesised? From what? What year? By who?1) Sulphonamides
2) The dye prontosil
3) 1935
4) Beyer in Germany - 8What is ampicillin?A semi-synthetic anti-microbial; group added to penicillin
- 9What are quinolines?Adapted penicillin
- 10What are the ways in which antibiotics can be classified?1) Based on spectrum of activity (broad vs. narrow)
2) Based on mode of action (bacteriostatic vs. bactericidal) - 11Give examples of a bactericidal antimicrobials (5)1) Penicillins
2) Cephalosporins
3) Fluoroquinolones
4) Glycopeptides
5) Monobactams - punch holes into membrane - 12Give examples of bacteriostatic antimicrobials (6)1) Sulphonamides
2) Chloramphenicol
3) Tetracylines
4) Macrolides
5) Trimethoprim
6) Clindamycin - 13What are chloramphenicol used to treat?Conjunctivitis
- 14What can determine whether a antimicrobial is bacteriostatic or bactericidal (most have the capacity to be either)? (3)1) Dose
2) Duration of exposure
3) The state of invading bacteria - 15Give three examples of antimicrobials which are effective against gram +tive aerobes ONLY.1) Glycopeptides
2) Bacitracin
3) Penicillin - 16Give example of a narrow spectrum antimicrobial which is only effectives Gram -tive aerobes.Polymixins
- 17Give an three examples of narrow spectrum antimicrobials which are effective at treating both gram +tive and gram -tive aerobes.1) Aminoglycosides
2) Sulfonamides
3) Actinomycin - 18Give an example of a narrow spectrum antimicrobial which is effective against anaerobesNitroimidazoles
- 19Give five examples of broad spectrum antimicrobials.1) Tetracyclines
2) Phenicols
3) Fluoroquinolones
4) Third generation cephalosporins
5) Fourth generation cephalosporins - 20What does the spectrum of activity of antimicrobials depend on?1) Mode of action of that antibiotic
2) Type of bacteria - 21How is the therapeutic index calculated?Therapeutic index = TD50/ED50
i.e. dose of the drug (IN PLASMA) which is toxic in 50% of the population divided by the dose which is effective in 50% of the population. - 22What type of therapeutic index do aminoglycosides have? Penicillins?1) Low TI
2) High TI - 23How does antibiotic selectivity occur? (4)1)Biochemistry of bacteria is different - bacteria produce vit K
2) Bacterial cell wall and membrane while animal cell only has a plasma membrane
3) Bacteria ribosomes 70S (50S + 30S); Eukaryotes 80S (40S + 60S)
4) DNA directed RNA polymerases are different - 24Why do you have to be careful when using antimicrobials which target bacterial ribosomes?Mitochondria also have 70S ribosomes
- 25How many conserved regions are there in bacteria?~200
- 26How many conserved bacterial regions are exploited? What are they?4
1) Inhibition of bacterial cell wall synthesis
2) Inhibition of bacterial protein synthesis
3) Inhibition of DNA transcription and replication
4) Inhibition of RNA synthesis and replication - 27How many targets/pathways do even the most successful antibiotics hit? What are they?Three
1) The ribosome (inhibit bacterial protein production)
2) Cell wall synthesis
3) DNA gyrase or DNA topoisomerase - 28What class of antibiotics interfere with cell wall synthesis? What type of antibiotic is included within this?1) Beta Lactams
2) Penicililns - 29How does vancomycin exert its effect on bacteria?Interferes with cell wall synthesis
- 30How do polymyxins exert their antimicrobial effect?Punch holes in bacterial cell wall membrane
- 31Which two classes of antibiotics interfere with the 30S subunit of bacterial ribosomes?1) Tetracyclines
2) Aminoglyosides - 32How do streptogramins, chloramphenicol and clindamycin interefere with bacteria?Target the 50S subunit of bacterial ribosomes
- 33How does rifampin exert an effect on bacteria?Targets bacterial RNA polymerase (interferes with nucleic acid synthase)
- 34How do quinolones interfere with bacteria?Interfere with DNA gyrase and therefore bacterial nucleic acid synthesis
- 35How do sulfonamides and trimethoprim damage bacteria?Affect folate synthesis and therefore interefere with nucleic acid synthesis
- 36Describe the structure of beta-lactam ring. Give two examples of antibiotics which contain B-lactam ring? What other ring does it contain?1) C4NO (contains a nitrogen group)
2) Penicillin and Cephalosporins
3) Thiazolidine ring (contains a sulphur) - 37What do most beta-lactam antibiotics do?Inhibits a specific step in the synthesis of peptidoglycans (most common mechanism on antibiotics)
- 38Describe the typical structure of a cell wall of S. aureusAlternating sugars along the backbone - N-acetylglucosamine (NAG), N-acetylmuramic acid (NAM). Each sugar is attached to four amino acids. Amino acid chains are linked by a five pentaglycine link.
- 39What are NAG and NAM derived from?Glucose
- 40What are the four amino acids attached to each sugar?1) L-Alanine
2) L-Lysine
3) D-Glucamine
4) D-Alanine - 41Which enzyme is responsible for the synthesis of the formation of the pentaglycine cross link to be synthesised (and thus the cell wall)? What happens the bridge is formed?1) Transpeptidase
2) Before there was a pentaglycine cross link there was a fifth amino acid on the chain (D-alanine) which is removed by transpeptidase. - 42How does penicillin interfere with transpeptidase?The structure of penicillin is very similar to the structure of the substrate for the transpeptidase (two alanines joined together - mimics dialanine peptide). Transpeptidase enzyme interacts with penicillin forming penicilloylated transpeptidase enzyme - penicillin covalent activates serines in the active site, preventing it from functioning. Transpeptidase is a penicillin binding protein
- 43What therefore are the 3 roles of transpeptidase1) Formation of crosslinks between D-amino acids
2) Hydrolysis of peptide bonds
3) Hydrolyses peptide bond in penicillin - 44What class of antibiotics do vancomycin and teicoplanin belong to?Glycopeptide antibiotics
- 45Describe the structure of glycopeptide antibiotics7 amino acids - heptapeptide antibiotics
- 46What type of bacteria can glycopeptide antibiotics target?Gram-positive bacteria - cannot penetrate the wall of gram-negative bacteria.
- 47How do glycopeptide antibiotics interefere with bacteria?Forms hydrogen bonds between the two terminal alanines of the 5-amino acid chain (attached to the NAG and NAM sugars). Thus the terminal alanines are masked by the vancomycin and are not available to form the pentaglycine cross link - no cell wall biosynthesis
- 48How is vancomycin delivered? What is it used to treat?1) Intravenously
2) Allergic patients or for MRSA - 49What is vancomycin considered a last resort medication for?Treatment of septicaemia and lower respiratory tract, skin, and bone infections caused by Gram-positive bacteria
- 50What are the two types of polymyxin? What do they do? What are they used to treat?1) B and E (Colisitin)
2) Membrane disrupting agents - cationic antimicrobial agents
3) paediatric diarrhea - 51How is colistin used? Why?As a last resort - resistant has started to develop (mainly due to use in pig farming in china)
- 52How do polymyxins work? Which type of bacteria do they taregt?Compete and displace cations (Ca2+ and Mg2+) from phosphate and bind to negatively charged PLS (lipopolysaccharide) and PL (phospholipid). This destabilises the outer membrane. The polymyxin can then enter the periplasmic space. This damages the inner membrane. Increases membrane permeability - leakage from cell; osmotic lysis.
- 53What type of bacteria do polymyxins target?Gram-negative
- 54How does chloramphenicol interefere with protein synthesis?Binds to 50S ribosomes - inhibits formation of peptide bond between already bound amino acid and formation of peptide bond.
- 55What are the three other classes of antibiotics which inhibit protein synthesis?1) Macrolides
2) Tetracylines
3) Aminoglycosides - 56Give two examples of macrolides and explain how they works. Which other class of antibiotics does the same thing (give an example). What are they good at treating?1) Erythromycin; clarithomycin - bind to the 50S subunit and prevents movement (of the transfer tRNA) along mRNA.
2) Lincosamides -clindamycin
3) Anaerobic bacteria - bone and joint infections - 57How do tetracyclines function? Give two examples.1) Prevent tRNA from binding to the mRNA-ribosome complex by binding to the 30S subunit. Prevents in the incorporation of amino acids and results in incomplete non-functional proteins.
2) Doxycycline and minocycline - 58Give an example of an aminoglycoside and explain how it worksStreptomycin - changes the shape of the 30S subunit causing the code on the mRNA to be read incorrectly. Prevents initiation of protein synthesis
- 59Which type of bacteria is streptomycin effective against?M tuberculosis
- 60Give three more examples of aminoglycosides - what type(s) of bacteria are they effective against?1) Gentamicin; tobramycin; amikacin
2) Most gram-negative and gram-positive bacteria - 61How are aminoglycosides delivered? What can they cause at high doses?1) Intravenous
2) Renal impairment and hearing loss. - 62What class of antibiotics do tetracyclines, macrolides and lincosamides all belong to? What are they good at treating and why?1) Bacteriostatic
2) Intracellular pathogens - achieve high intracellular concentrations in host tissues. - 63Give examples of quinolones/fluoroquinolones. What type of antibiotic are they (spectrum)?1) Ciprofloxacin and levofloxacin
2) Broad spectrum - bactericidal synthetic antimicrobials - 64What is the mechanism of action of quinolones and fluoroquinolones?Inhibit DNA synthesis and promote DNA cleavage by binding to topoisomerase II (DNA gyrase) and topoisomerase IV (DNA topoisomerase).
- 65What is the function of topoisomerase II (DNA gyrase) and topoisomerase? How does antibiotic binding interact with this?Responsible for nicking the DNA to prevent DNA supercoiling, and then repairs the nick. Once the antibiotic binds DNA cleavage will still occur but the synthesis of the DNA will not.
- 66What type of pathogen are quinolones and fluoroquinolones active against? Give three examples - why can't antibiotics which damage cell walls have an effect? Where are these types of bacteria increasingly being seen?1) Intracellular
2) Chlamydia spp, legionella spp, mycoplasma spp - very small, no cell walls.
3) STIs
One of the most widely prescribed antibiotics (particularly fluoroquinolones) - 67What is rifampicin? What are they particularly effective against?1) Inhibitor of prokaryotic transcription initiation - only binds to DNA dependent RNA polymerase.
2) Gram-positive bacteria - 68Why is rifampicin good at treating TB meningitis? What else can it be used to treat?1) Lipophilic and so can cross the BBB
2) Can be used in combination with other drugs to treat mycobacterium tuberculosis and some staphylococcal infections. - 69What do sulphonamides do? Give two examples?1) Folic acid inhibitors
2) Co-trimoxazole-trimethoprim/sulfamethoxazole - 70What system do sulphonamides take advantage of?Bacterias synthesise their own folic acid. p-Aminobenzoic acid (PABA) is a precursor of folic acid. Sulphonamides are a structural analogue of PABA.
- 71What is folic acid used for?Production of DNA (purines
- 72What is the bacteria only part of the biosynthesis of purines?1) Pteridine + p-Aminobenzoic acid + glutamic acid
2) Dihydropteroate synthase converts those into dihydropteroic acid.
3) dihydropteroic acid is converted into dihydrofolic acid by addition of glutamate - 73What is the rest of the biosynthesis pathway (eukaryotes + prokaryotes)?1) Dihydrofolic acid is converted into tetrahydrofolic acid by dihydrofolate reductase and the into purines
- 74How precisely do sulphonamides interfere with folic acid biosynthesis?Competitive inhibitor of dihydropteroate synthase (as they are structural analogues of PABA)
- 75What stage of biosynthesis of purines do trimethoprim interfere with? Why is this safe to use in humans?Conversion of dihydrofolic acid into tetrahydrofolic acid by dihydrofolate reductase. Human dihydrofolate reductase is resistant to trimethoprim.
- 76Who needs to be immunised and against what?1) Students (university, since Aug. 2015) - meningitis A/C/W/Y
2) Babies and children - Death (measles, pertussis); Clinical manifestation (polio-virus)
3) Travellers/workers abroad - latent infection (Hep B)
4) Healthcare workers - chickenpox, TB
5) Elderly -pneumococcal (sometimes) and flu
6) Pregnancy - fetal infection (rubella) and flu
7) At risk patients - chronic respiratory or heart disease - 77What is an ideal vaccineTo produce the same immune protection which usually follows a natural infection but without causing the disease - generates long-lasting immunity and interrupts the spread of infection
- 78What is a primary failure?Inadequate response to initial vaccination - e.g. 10% measles and mumps vaccines
- 79What is a secondary failure?Initial immunity decreases over time - boosters required.
- 80What is the issue surrounding inactivated vaccinesfrequency of adverse events increases with number of doses (e.g. tetanus and pertussis). If there is a good secondary immune response in may cause inflammation (i.e. a sore arm). Can present with milder forms of the condition.
- 81Why might some individuals produce an immune response?If they are immunocompromised of immunosuppressed - e.g. cancer or HIV patients
- 82What do most antibacterial vaccines offer? What are the two types?1) Protection against pathogenicity of toxins
2) Live attenuated (weakened) or inactivated. - 83How are live attenuated bacterial vaccines produced? What is the difference compared to more virulent strains?1) Bacteria are cultured over a long period of time
2) Multiply more slowly than virulent strains - 84What is the BCG? TY21a (live typhoid vaccine)? CBD 103-HgR (cholera vaccine)?1) Bovine strain of tuberculosis
2) Strain of salmonella typhi bacteria - oral typhoid
3) Live attenuated vibrio cholerae and a recombinant cholera toxin B subunit (oral) - 85How are inactivated bacterial vaccines produced?Chemical treatment (formalin), heat or purification of polysaccharide components - large amount of antigen produced (antigen only) without the risk of infection
- 86What are the different forms of inactivated bacterial vaccines? (3)1) Whole killed bacteria
2) Protein subunits
3) Toxoid (inactivate toxins) - 87Give four examples of whole killed bacteria vaccinations.1) Anthrax
2) Cholera
3) Plague
4) Pertussis - 88Give an example of a vaccine which uses a protein subunitacellular pertussis
- 89Give two examples of a toxoid vaccinationTetanus and diptheria
- 90What are the two types of polysaccharide vaccines?1) Pure polysaccharide
2) Conjugate vaccines - 91Give three examples of pure polysaccharide vaccines. What do they predominantly lead to the production of? How immunogenic are they?1) Pneumococcal, meningococcal, and salmonella typhi
2) Produce IgM
3) Not very immunogenic within 2 years - 92What are conjugate vaccine? Give three examples. How immunogenic are they?1) Polysaccharide linked to a bacterial protein carrier
2) Hib B; pneumococcal; meningococcal A and C
3) Immunogenic - last more than 2 years - 93How do vaccinations affect the humoral immune response?1) Leads to production of IgM (short lived) via Th Helper cell interaction (lag period first)
2) TH2 cells also leads to production of memory cells which lead to the rapid production of IgG upon re-encountering the antigen (or in response to booster). No/very little lag phase. - 94Which combined vaccination is given at 6 weeks? Single vaccinations?1) 6 in 1: diphtheria, tetanus, pertussis, polio, haemophilus influenzae type b (Hib) and hep B
2) Pneumococcal (PCV), rotavirus, Men B - 95Which combined vaccination is given at 12 weeks? Single vaccination?1) 6 in 1 - second dose
2) Rotavirus - second dose - 96Which combined vaccination is given at 16 weeks? Single vaccination?1) 6 in 1 - second dose
2) Pneumococcal - second dose; Men B - second dose - 97Which combined vaccination is given at 1 year? Single vaccination?1) MMR; Hib - 4th dose; MenC - first dose
2) Pneumococcal - third dose; Men B - third dose - 98Which combined vaccination is given at 2-8 years? Single vaccination?1) None
2) Flu vaccine - 99Which combined vaccination is given at 3 years and four months? Single vaccination?1) MMR second dose; 4 in 1 (diphtheria, tetanus, pertussis and polio)
2) None - 100Which combined vaccination is given at 12-13 (girls only)? Single vaccination?1) HPV - 2 injections (6-12 months apart)
2) None - 101Which combined vaccination is given to teenagers and first year university students?? Single vaccination?1) 3 in 1 diphtheria, tetanus and polio; Men A/C/W/Y
- 102What five factors are contributing to antimicrobial resistance?1) Poor sanitation
2) Poor hygiene
3) Antibiotic misuse
4) Immunocompromised patients
5) Travel - 103How much do antibiotics increase our lifespan by?~20 years
- 104What are antibiotics essential for?Invasive surgery and treatments like chemotherapy
- 105How many deaths per year in Europe are attributed to multi-drug resistance?25,000 deaths
- 106Define intrinsic resistance.Ability to resist the action of that antibiotic as a result of inherent structural or functional characteristics.
- 107What is acquired resistance? What transfers this resistance?Mutations and horizontal gene transfer-plasmids (e.g. hospital setting - poor adherence to infection control protocols). Plasmids during conjugation reactions.
- 108What is MRSA?methicillin resistant staphylococcus aureus
- 109What can MRSA cause?Endocarditis and septicaemia.
- 110How is MRSA resistant to penicillin?An alternative transpeptidase enzyme is produced which has much lower affinity for B-lactams (MecA gene).
- 111What can antimicrobial resistant E. coli cause? How is it resistant?1) Diarrhea, UTIs, neonatal meningitis and septicaemia.
2) It is an enterobacteriaceae - produces extended-spectrum B-lactamase (ESBL) which damage the B-lactam ring - 112What are carbapenems used for? Give an example.1) Reserved for serious, highly drug-resistant gram-negative pathogens as they are resistant to most B-lactamases.
2) Klebsiella - can cause surgical site infections - 113What is the major concern with carbapenems?Rise of carbapenem resistant - extended range of ESBL activity to produce carbanpenemases. Bacteria are becoming resistant to cephalosporins (same mechanism of B-lactams but much more resistant to B-lactamases).
- 114How many deaths per year are caused by resistant pathogens~40,000?
- 115What are the three intrinsic mechanism of antimicrobial resistance.1) Gram-negative has a less permeable outer membrane which forms a permeability barrier (e.g. vancomycin cannot cross)
2) Efflux pumps are active transporters which transport a large number of unrelated antibiotics - multidrug resistance. - 116What are the 5 types of acquired antibiotic resistance?1) Drug inactivation - hydrolysis or other modification
2) Activation of drug pumps - antibiotic efflux or poor penetration into bacterium
3) Modification of target - by mutation or posttranslational modification
4) Alternative metabolic pathways - occurs when mutations change the target enzyme - 117Which antibiotics are susceptible to degradation/modification?B-lactams, aminoglycosides and macrolides
- 118Which antibiotic can B-lactamases hydrolyse?Penicillins, cephalosporins, monobactams and carbapenems.
- 119What are isolates which are resistant to all B-lactam antibiotics called? How is B-lactam resistance spread?1) Extended spectrum beta lactamases
2) Clones and plasmids - 120What are the two beta-lactamase inhibitors which are often given with penicillins?Clavulanic acid and tazobactam (both are B lactams)
- 121What is used to treat resistant strains of S. aureus, E. coli and H. influenzae?Co-amoxyclav = amoxicillin and clavulanic acid
- 122How do efflux pumps lead to increased resistance? How is this spread? What range of antibiotics can be inhibited?1) Overexpression of pumps
2) Integrated into plasmids and can transfer between bacteria
3) Some of the pumps (broad range antibiotic efflux pump as opposed to single antibiotic pump in inner membrane + porin in the outer membrane) have two binding pockets allowing the binding and transport of a wide range of antibiotics. E.g. P. aeruginosa and S. aureus - 123How do mutations in target proteins lead to resistance?Prevent antibiotic binding but allow the protein to function.
- 124How does bacterial protein point mutations and antibiotics interact? Give an example.1) Antibiotic use can select for a point mutation which can then be transferred at high frequency by homologous recombination.
2) S. pneumoniae after linezolid use - 125Give an example of how modifications of target proteins causes resistance to macrolides.Erythromycin induces the expression of bacterial erythromycin ribosome methylase (erm) - this methylates the 30S ribosome and changes the drug binding site. Prevents macrolides from binding 50S.
- 126Give an example of an antibiotic resistance cause by bypass mechanisms and explain how it works.Trimethoprim resistance - drug resistant dihydrofolate reductase acquired via plasmids or transposons - dfr genes encode resistant DHFR. Spontaneous mutations encode resistant DHFR. Gene duplication then passes on resistance.
- 127When was the last antibiotic discovered which can treat systemic bacterial infections?1987
- 128What is colistin (polymyxin E for)Antibiotic of last resort for nosocomial or hospital acquired infections (HAI) but is toxic and now horizontal gene transfer has results in resistant pathogens.
- 129What has teixobactin shown to be successful in treating? What is not able to treat?1) Animal testing has shown that it is effective against clostridium difficile, mycobacterium tuberculosis and staphylococcus aureus BUT are all gram-positive.
2) Doesn't work against gram-negative bacteria which include some of the most worrying antibiotic-resistant pathogens, such as klebsiella, E. coli and pseudomonas. - 130What are the four main solutions to the current crisis in antimicrobial resistance?1) More effective prevention in antibiotic use
2) Targeted treatments (limit use of broad spectrum antibiotics)
3) More informed clinical decisions
4) Public education