Antibiotics Flashcards
What are Diesinfectants, Antiseptics and Antibiotics?
Disinfectants - applied to inanimate objects
Antispetics - sufficiently non-toxic to be applied to living tissue (hand sanatizer)
Antibiotics - produced by bacteria and fungi, exploited by humans
Who discovered penicillin
Alexander Flemming in 1928
- discovered it by accident from leaving staph plates out and observing that the staph could not grow around a contaminating mold
- won nobel prize in physiology and medicine (1945)
Antibiotics are…
- The most effective therapeutic treatment against bacterial infections
- enables chemotherapy, organ transplantation and all invasive surgeries
What are 2 major problems posed by antibiotics?
- Diminished interest from pharmaceutical companies to develop new antibiotics
- Bacterial resistance to antibiotics always happens
- because of resistance no guarentee that a drug made will be used for a long time
- not many make it to the last stage of testing
When was the golden age of antibiotics?
1940-1960 = 11 discovered
1960 - present = 4 discovered
How old is antibiotic resistance?
Ancient…DNA from frozen permafrost (~30,000 years old) found antibiotic resistance genes (still able to work)
What are the 2 ways antibiotics work?
Kill bacteria (bactericidal) Stop them from gowing (bacteriostatic)
How does one measure antibiotic activity?
Minimum Inhibitory Concentration (MIC)
- Series of culture tubes with varying [agent]
- check for visible growth
- MIC = lowest [agent] that inhibits growth
Zone of Inhibition
- Antibiotic strips on a plate of bacteria
- most effective antibiotic will have largest zone of inhibition where the bacteria was not able to grow
How do antibiotics work?
Target essential bacterial components not present (or different) in eukaryotic cells
- cell wall synthesis
- protein synthesis
- DNA/RNA synthesis
- Folate Synthesis
- Cell membrane alteration
Describe Beta-Lactam Antibiotics
e. g. Penicilin
- contains a Beta lactam ring
- Binds to bacterial penicillin binding proteins
- Stops peptide cross-links = weak cell wall = cell death
How can bacteria be resistant to penicillin, how can this be countered?
Resistance: Beta-lactamase produced by some bacteria can destroy the ring
Response to resistance: Chemically modified penicillin can’t be cleaved by beta-lactamases
- Some bacteria produce a different penicillin binding protein encoded by ‘mec’ (PBP2a)
- This doesn’t bind methicillin and is therefore resistant to it
What does Vancomycin do?
Inhibits cell wall synthesis in Gram+ bacteria
- glycopeptide antibiotic
- last resort drug
- Binds to peptide linkage at terminal D-Ala-D-Ala inhibiting transpeptidation
Resistance: Bacteria can change to D-Ala-D-Lac and vancomycin can no longer bind
- encoded by van genes
What do Protein synthesis inhibitors do?
Protein synthesis inhbitors:
- Bacteria contain 70S (30S + 50S)ribosomes
- Eukaryotes contain 80S (40S + 60S)
- Many antibiotics target bacterial ribosomes and block translation
What do Folic acid (vitamin B9 for humans) inhibitors do?
Trimethoprim and Sulfonamides
- Folic acid = thymidine synthesis in bacteria
- Must synthesize their own
- Inhibition of folic acid synthesis blocks DNA replication
What do DNA/RNA synthesis inhibitors do?
e. g. Flouroquinolones
- interfere with DNA gyrase needed for supercoiling of DNA
e. g. Rifampicin
- Inhibits bacterial RNA polymerase
What is Cell membrane alteration?
Polymyxin B
- Used on Gram-
- Bind to LPS
- Hydrophobic tail inserts and disrupts outer and inner membranes
What are some stratagies for antibiotic resistance?
Prevention of antibiotic entry
antibiotic modification
Efflux of antibiotic (pump out)
Alteration of antibiotic target (prevents binding)
Bypassing the antibiotic action (use environmnetal folic acid)
What are antibiotic resistance genes?
called R genes
- often encoded on mobile genetic elements (e.g. plasmids) leading to horizontal gene transfer -> superbugs
What are 3 ways to horizotally transfer genes?
Transformation: Uptake of short fragments of naked DNA by naturally transformable bacteria
Transduction: transfer of DNA from one bacterium into another via bacteriophages (viruses that infect bacteria)
Conjugation: Transfer of DNA via sexual pilus (cell-cell contact)
- very efficient
Paradoxically, the use of antibiotics…
actively selects for resistant bacteria
What are overuses/misuse of antibiotics?
Empiric use (blinded use)
- acceptable for septic shock
- Increase use of broad spectrum agents (kills more than necessary)
- Pediatric use for viral infections
- Patients who do not complete the course (surviving bacteria will be resistant)
- Antibiotics in animal feed
What are the ESKAPE bacteria?
Enterococcus faecium Staphylococcus aureus Klebsiella species Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter species - Cause 2/3 of all health care associated pathogens
Describe Enterococci
Species: faecalis, faecium(less virulent, more drug resistant)
- Gram+, non-motile, grows in chains
- Normal colonizers of intestinal tracts in mammals
Causes: UTIs, endocarditis, surgical infections
What is VRE?
Vancomycin resistant enterococci
- first reported in 1989, now globablly disseminated
- has can genes which give resistance
- nosocomial (hospital aquired infection)
Describe Acinetobacter baumannii
- Gram- aerobe, Iraqibacter, nosocomial (hospital aquired infection)
- found on the skin of healthy people
- Causes: UTI ventilator pneumonia, bacteremia and spesis
- can be resistant to virtually all antibiotics
Describe Klebsiella pneumoniae
Gram-, facultative anaerobe, important cause of noscomial pneumonia
- produces a capsule which is resistant to multiple antibiotics
What is NDM-1
- New delhi Metallo-beta-lactamase-1(carbapenems)
- Beta-lactamase resistant with broad spectrum activiy (lots of resistance)
- NDM-1 is now widespread in other Gram- bacteria
How long does antibiotic resistnace take to evolve?
If widely used, 1-2 years
Penicillin
- introduced in 1941, resistant S. aureus in 1942
Methicillin
- introduced 1959, resistant S. aureus in 1961
Vanomycin
- introduced 1950s, reintroduced in `1960s, resistance in enterococci in 1989
- emergance of Multi-resistant S. aureus (MRSA) - 1999
- linezolid introduced to treat pneumococci (2000)
- Linezolid resistnace reported in S. aureus and VRE(2001)
- Vanomycin resistant S. aureus (VRSA)
