Antimicrobial therapy
• Antimicrobials – agent which either kills or stops microbial growth
o Antibiotics
o Antivirals
o Antiparasitic, antimalarials
o Antifungals
• Antibiotics underpin modern medicine
o Given as prophylactic to cancer patients
o Surgery
o Bites wounds
o Minor ailments – e.g., ingrown nail
o Diabetes
o Complications in pregnancy, UTIs etc
• Infection prevention required
o Behavioural changes when prescribing, increased stewardship
o Novel solutions, vaccines, phage therapies
o Surveillance – incidence rates = accurate statistics
o Engage and educate the public
• Bacteria exchange of genetic material
o Transformation
▪ Bacteria pick up genes on plasmids in environment
▪ Seen with resistant genes of Klebsiella in water
o Transduction
▪ Phage-infected bacterial cell releases phage carrying gene which is then inserted into
another bacterial cell
▪ When using phage therapy, don’t know the genetic changes that occur in the
bacteria due to the phage
▪ There is no monitoring of phage-infected bacteria and their genetic alterations
currently
o Conjugation – horizontal gene transfer via pili
• Discovery of antibiotics
o Penicillin G
▪ 1929 Alexander Fleming characterised antibiotic from fungus Penicillum
chysogenum/notatum)
▪ Beta-lactam penicillin G
▪ 1939 Florey and Chain developed process for large scale production of penicillin
▪ Used on soldiers during WW2
▪ General use in 1945
▪ Fleming, Florey, and Chain warned at the start to building of resistance in bacteria to
penicillin by exposing bacteria to sub-lethal concentrations
o ‘Golden era’ of antibiotic discovery 1940s-1960s
▪ 1940s – penicillin, gramicidin, neomycin, streptomycin, cephalosporin
▪ 1950s – chloramphenicol, chlortetracycline, polymyxin, erythromycin, vancomycin,
virginiamycin
▪ 1960s – rifamycin
o Last antibiotic discovered was daptomycin in 2003
o Antibiotics of golden era were overmined, overprescribed and overused (no stewardship or
preservation) = resistance
o Money needed at every step of antibiotic discovery pipeline – very expensive process
o No progression on diagnostics – still use agar plates (created in early 1940s)
• Antibiotic mode of action
o Inhibition of protein synthesis
, ▪ Aminoglycosides – streptomycin
▪ Chloramphenicol
▪ Macrolides
▪ Tetracyclines
▪ Oxazolidinones – linezolid
▪ Streptogramins – pristingamycin
o Inhibition of nucleic acid (DNA) synthesis
▪ Quinolines – ciprofloxacin
o Inhibition of cell wall synthesis
▪ Beta-lactams – penicillin, carbapenem
▪ Glycopeptides – vancomycin (creates pores in crosslink between NAG and NAM)
o Disruption of cell membrane functions
▪ Lipopeptides – daptomycin
o Inhibition of RNA synthesis
▪ Ansamycins – rifamycin
o Prevent growth/multiplication
▪ Sulphonamides – sulphanilamide
• Antibiotics used in combination to attack multiple bacterial processes
o Need a balance between high concentration of antibiotics to kill bacteria but without long
term effects to patient – many doctors will choose a patient to live with kidney/liver
damage than die from infection
• Broad spectrum antibiotics effective against a wide range of bacteria
• Narrow spectrum antibiotics effective against specific bacteria
• Bacteriostatic antibiotics inhibit bacterial growth – e.g., beta-lactams, glycopeptides, colistin
• Bactericidal antibiotics kill bacteria – e.g., macrolides, tetracyclines, chloramphenicol
• Antibiotic resistance on the rise in a lot of antibiotics 0 occurs when bacteria change in response to
use of antibiotics, they evolve to survive
• Human impact
o A global issue
o 10million deaths by AMR resistance by 2050 – more than cancer and diabetes combined
o Burden of infectious comparable to influenza, TB, and HIV/AIDs combined
o Estimated £1 trillion of GDP lost due to efforts combating AMR in patients (without
appropriate R&D) – socioeconomic issue
o Should have an international AMR meeting (like COP with global warming)
• Antimicrobials – agent which either kills or stops microbial growth
o Antibiotics
o Antivirals
o Antiparasitic, antimalarials
o Antifungals
• Antibiotics underpin modern medicine
o Given as prophylactic to cancer patients
o Surgery
o Bites wounds
o Minor ailments – e.g., ingrown nail
o Diabetes
o Complications in pregnancy, UTIs etc
• Infection prevention required
o Behavioural changes when prescribing, increased stewardship
o Novel solutions, vaccines, phage therapies
o Surveillance – incidence rates = accurate statistics
o Engage and educate the public
• Bacteria exchange of genetic material
o Transformation
▪ Bacteria pick up genes on plasmids in environment
▪ Seen with resistant genes of Klebsiella in water
o Transduction
▪ Phage-infected bacterial cell releases phage carrying gene which is then inserted into
another bacterial cell
▪ When using phage therapy, don’t know the genetic changes that occur in the
bacteria due to the phage
▪ There is no monitoring of phage-infected bacteria and their genetic alterations
currently
o Conjugation – horizontal gene transfer via pili
• Discovery of antibiotics
o Penicillin G
▪ 1929 Alexander Fleming characterised antibiotic from fungus Penicillum
chysogenum/notatum)
▪ Beta-lactam penicillin G
▪ 1939 Florey and Chain developed process for large scale production of penicillin
▪ Used on soldiers during WW2
▪ General use in 1945
▪ Fleming, Florey, and Chain warned at the start to building of resistance in bacteria to
penicillin by exposing bacteria to sub-lethal concentrations
o ‘Golden era’ of antibiotic discovery 1940s-1960s
▪ 1940s – penicillin, gramicidin, neomycin, streptomycin, cephalosporin
▪ 1950s – chloramphenicol, chlortetracycline, polymyxin, erythromycin, vancomycin,
virginiamycin
▪ 1960s – rifamycin
o Last antibiotic discovered was daptomycin in 2003
o Antibiotics of golden era were overmined, overprescribed and overused (no stewardship or
preservation) = resistance
o Money needed at every step of antibiotic discovery pipeline – very expensive process
o No progression on diagnostics – still use agar plates (created in early 1940s)
• Antibiotic mode of action
o Inhibition of protein synthesis
, ▪ Aminoglycosides – streptomycin
▪ Chloramphenicol
▪ Macrolides
▪ Tetracyclines
▪ Oxazolidinones – linezolid
▪ Streptogramins – pristingamycin
o Inhibition of nucleic acid (DNA) synthesis
▪ Quinolines – ciprofloxacin
o Inhibition of cell wall synthesis
▪ Beta-lactams – penicillin, carbapenem
▪ Glycopeptides – vancomycin (creates pores in crosslink between NAG and NAM)
o Disruption of cell membrane functions
▪ Lipopeptides – daptomycin
o Inhibition of RNA synthesis
▪ Ansamycins – rifamycin
o Prevent growth/multiplication
▪ Sulphonamides – sulphanilamide
• Antibiotics used in combination to attack multiple bacterial processes
o Need a balance between high concentration of antibiotics to kill bacteria but without long
term effects to patient – many doctors will choose a patient to live with kidney/liver
damage than die from infection
• Broad spectrum antibiotics effective against a wide range of bacteria
• Narrow spectrum antibiotics effective against specific bacteria
• Bacteriostatic antibiotics inhibit bacterial growth – e.g., beta-lactams, glycopeptides, colistin
• Bactericidal antibiotics kill bacteria – e.g., macrolides, tetracyclines, chloramphenicol
• Antibiotic resistance on the rise in a lot of antibiotics 0 occurs when bacteria change in response to
use of antibiotics, they evolve to survive
• Human impact
o A global issue
o 10million deaths by AMR resistance by 2050 – more than cancer and diabetes combined
o Burden of infectious comparable to influenza, TB, and HIV/AIDs combined
o Estimated £1 trillion of GDP lost due to efforts combating AMR in patients (without
appropriate R&D) – socioeconomic issue
o Should have an international AMR meeting (like COP with global warming)
