Antimicrobial Therapies Flashcards
What type of antibiotic is prontosil?
Sulphonamide
What is prontosil used to treat? (4)
- UTIs
- RTIs (respiratory tract)
- Bacteraemia
- HIV prophylaxis
What are the 9 types of antibiotic?
(Guys Let’s Do Something to Mitigate Bacterial Antibiotic Resistance Quickly!)
- Glyopeptides
- Linezoid
- Daptomycin
- Sulfonamides
- Macrolids
- Beta-lactams
- Aminoglycosides
- Rifamycins
- Quinolones
What may be used in conjunction with sulphonamides?
Trimethoprim
What type of bacteria does prontosil work against?
Gram positive
Which 5 antibiotics work against gram-positive bacteria only?
- Sulphonamides
- Beta-lactams
- Glycopeptides
- Linezoid
- Daptomycin
What are 2 examples of sulphonamides?
- Prontosil
- Sulpha-methoxazole
How do beta-lactams act as antibiotics?
Cell wall
- Bind to penicillin binding proteins (PBPs)
- PBPs catalyse peptidoglycan synthesis
- Cell wall can’t be synthesised
What are 2 examples of beta-lactams?
- Penicillin
- Methicillin
What type of antibiotic is penicillin?
Beta-lactam
What type of antibiotic is methicillin?
Beta-lactam
What do beta-lactams bind to?
PBPs
What is the shape of a beta-lactam ring?
Square
When are antibiotics administered? (3)
- Bacterial infections
- Surgery —> prevent infection
- Cancer therapies —> weakened immune system
What are the 4 antimicrobial mechanisms?
- Inhibit peptidoglycan cell wall synthesis
- Inhibit translation
- Inhibit transcription
- Target cell membrane
What is an antibiotic?
Antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms
What are most antibiotics produced by today? (2)
- Soil-dwelling fungi
- Bacteria
Which antibiotics are produced by soil-dwelling fungi? (2)
- Penicillin
- Cephalosporium
Which antibiotics are produced by bacteria?
- Streptomyces
- Bacillus
What is the difference between bactericidal and bacteriostatic antibiotics?
- -Cidal —> kills
- -Static —> stops growth
What is an antiseptic?
Topical chemical that kills/inhibits microbes
What does antimicrobial mean?
Chemical that selectively kills/inhibits microbes
What is the main problem of antibiotics?
Resistance
What is the antibiotic breakpoint?
Concentration of drug past which bacteria will develop resistance (at MIC)
What is the minimal inhibitory concentration (MIC)?
Lowest AB concentration required to inhibit growth
How are antibiotic dosages decided?
MIC
Why does the use of antibiotics lead to resistance?
Act as selection pressure
What are the 3 steps of bacteria developing antibiotic resistance?
- Mutation —> bacteria in population has AB resistance
- Selection pressure of AB
- AB resistant bacteria outcompete non-resistant
What type of gene transfer also leads to other species of bacteria gaining resistance?
Horizontal
How long after the arrival of a new antibiotic does resistance usually emerge?
Soon
What does antibiotic resistance lead to? (5)
In mortality, morbidity, cost
1. Inc time for therapy effectivity
2. Treatment requires other approaches eg. surgery/IV
3. Expensive therapies used
4. More toxic drugs used
5. Less effective ABs used
Which 6 gram-negative bacteria are multi-drug resistant?
- P. aeruginosa
- E. coli
- Salmonella
- A. baumannii
- N. gonorrhoeae
Which 5 gram-positive bacteria are multi-drug resistant?
- S. aureus
- S. pneumoniae
- C. difficile
- E. spp
- M. tuberculosis
How do aminoglycosides act as antibiotics?
Translation
-Target 30S ribosomal subunit —> interfere will RNA proofreading —> inhibit protein synthesis —> damage cell membrane
What are 2 examples of aminoglycosides?
- Gentamicin
- Streptomycin
What type of antibiotic is gentamicin?
Aminoglycoside
What type of antibiotic is streptomycin?
Aminoglycoside
How does rifampin act as an antibiotic?
Translation
-Targets RpoB subunit of RNA polymerase —> inhibits translation
Why are there issues with rifampin compliance?
Turn secretions orange/red
What is a major issue of rifampicin regarding AB resistance?
Frequent spontaneous resistance
What is rifampin used to treat?
TB
How does vancomycin act as an antibiotic? (2)
Cell wall
- Targets Lipid II —> inhibit cell wall biosynthesis
- Targets D-ala residues —> inhibits cell wall crosslinks
Which 4 antibiotics have some toxicity?
- Sulphonamides
- Aminoglycosides
- Vancomycin
4.
Which 3 antibiotics are only bacteriostatic?
- Sulphonamides
- Linezoid
- Macrolides
How does linezolid act as an antibiotic?
Translation
- Binds to 50S rRNA subunit
What type of bacteria does linezolid work against?
Gram-positive
How does daptomycin act as an antibiotic?
Targets cell membrane
Why are antibiotics selectively toxic?
Can kill bacterial cells without harming host cells
Which organ can antibiotics collect in and cause issues?
Kidney
- If UTI —> good
What are the 4 mechanisms of antibiotic resistance?
- Altered target protein
- Inactivation of antibiotic
- Altered metabolism
- Decreased drug accumulation
How does an altered target site lead to AB resistance? (3)
- Mutation —> change target protein —> AB can’t bind
- Mutation —> different binding protein acquired
- Target site methylated
Which 2 bacteria acquired AB resistance via an altered target site?
- MRSA
- S. pneumoniae
How is MRSA resistant to beta-lactams?
Acquired PBP2a with low affinity for beta-lactams
How is streptococcus pneumoniae resistant to erythromycin?
erm gene acquired —> enzyme produced methylates target site in 50S ribosomal subunit
How does an inactivation of an antibiotic work?
Enzymic degradation/alteration
What are 2 examples of enzymes that can inactivate ABs?
- Beta-lactamase (bla)
- Chloramphenicol acety-transferase (cat)
think: BLAck CAT
What are 2 examples of broad-spectrum beta-lactamases?
- ESBL
- NDM-1
Why does altered metabolism lead to AB resistance? (2)
- Inc production of enzyme substrate —> out-compete AB inhibitor
- Switch to other metabolic pathway —> bypass AB target
How does AB resistance to sulphonamides occur?
Altered metabolism
- Inc production of PABA
- Switch to pathway that doesn’t use PABA
How does decreased drug accumulation work for AB resistance? (2)
- Dec penetration of AB into bacteria
- Inc efflux of AB out of bacteria
How do macrolides act as antibiotics?
Translation
- Target 50S ribosomal subunit —> prevent amino-acyl transfer —> truncates polypeptides
What are 2 examples of macrolids?
- Erythromycin
- Azithromycin
What type of antibiotic is erythromycin?
Macrolides
What type of antibiotic is azithromycin?
Macrolides
How do quinolones act as antibiotics? (2)
Transcription
1. Gram - —> target DNA gyrase
2. Gram + —> target topoisomerase IV
What is special about quinolone production?
Completely synthetic
What are the 3 sources of AB resistant genes?
- Plasmids
- Transponons —> allows gene transfer between plasmids and chromosome
- Naked DNA —> dead bacteria release DNA to environment
What are the 5 non-genetic mechanisms of AB resistance? (SPIBS)
- Slow growth
- Persistors
- Intracellular location
- Biofilm
- Spores
What are 5 reasons for AB treatment failure?
- Inappropriate choice of drug/dose/administration
- Poor AB penetration to target site
- AB resistance in commensal flora (eg. flora secrete beta-lactamase)
How is AB resistance identified?
- Swabs —> onto agar lorn
- AB test strips onto agar lorn
- Miro-dilution
- PCR detection of resistance genes
What are the 8 hospital acquired infections?
- MRSA
- VISA (vancomycin-insensitive)
- VRE (vancomycin-resistant enterococci)
- C. difficile
- E. coli
- P. aeruginosa
- A. baumannii
- S. maltophilia
What are hospital-acquired infections so common? (2)
- Many infected people
- Lots of AB use
—> Strong selective pressure
What are the 7 risk factors for hospital acquired infections?
- Many ill people - immunosuppressed
- Crowded wards
- Pathogens present
- Broken skin - after surgery/IV/catheter
- Intubation in indwelling devices
- AB therapy suppressing normal flora
- Single staff in contact with many patients - spread
How can antibiotics affect microbiota?
Out-compete flora
How is AB resistance being addressed? (5)
- Prescribing strategies
- Dec broad-spectrum AB use
- Quicker identification
- Combination therapy (eg. coamoxiclav)
- Knowledge of local strains
How can AB resistance be overcome? (2)
- Modify existing meds
- Combination of antibiotic and inhibitor
- eg. coamoxiclav = amoxicillin + clavulanic acid