Antibiotics, Pt. 2 Flashcards
Inhibitors of cell wall biosynthesis:
What was the first alternative to penicillins?
Cephalosporins
- considered to be among the safest antimicrobials
What is the mechanism of action of Cephalosporins? What causes resistance?
binds PBPs to interfere with peptidoglycan synthesis
bacterial β-lactamase production
How have the 5 generations of Cephalosporins developed?
- potent activity against G+, mediocre against G-
- not used in vet med - extended spectrum against G- with better cell penetration, and improved resistance to β-lactamase
- improved activity against G-, better cell penetration, higher binding to target
- improved resistance to β-lactamase, wider spectrum with higher activity against G+ and G-
- approved for treatment of critical MRSA infection
What is MRSA? What is the equivalent in animals? How is it treated?
methicillin-resistant Staphylococcus aureus (superbug), typically causing sepsis in humans
MRSP (methicillin-resistant Staphylococcus pseudintermedius), typically infected through wounds, surgical sites, and ears
5th generation Cephalosporins - Ceftobiprole
What 2 first-generation Cephalosporins are used in veterinary medicine? What is their therapeutic use?
- Cephalexin
- Cephalothin
antibiotic prophylaxis and treatment of infection in penicillin-intolerant patients of all species
What 6 third-generation Cephalosporins are used in veterinary medicine? What are their therapeutic uses?
- Ceftiofur - respiratory disease, cattle mastitis, UTI and soft tissue infections
- Cefoperazone - soft tissue infections and G- bacteremia in dogs
- Cefotaxime - G- sepsis, soft tissue infections, meningitis, and CNS infection in dogs, cats, and foals
- Cefpodoxime - skin infections in dogs and cats
- Cefixime - UTI, respiratory infections
What Cephalosporins are used for bovine mastitis and bacterial endocarditis in dogs?
Ceftiofur
Cefixime
(3rd gen)
What is the mechanism of action of Carbapenems? What is their spectrum like? What 3 are commonly used?
bind to penicillin-binding proteins to prevent cell wall biosynthesis
BROAD - G+, G-, aerobic, anaerobic, an Pseudomonas
Imipenem, Meropenem, Doriopenem
What causes resistance to Carbapenems?
β-lactamase (carbapenemases) that cleaves β-lactams
What is the mechanism of action of Monobactams? Which ones is most commonly used? What is its therapeutic use?
bind to penicillin-binding proteins (PBPs) to prevent cell wall biosynthesis
Aztreonam - reserve antibiotic to treat severe G- infections
What class of β-lactam is less likely for resistance to develop?
Monobactams - stable to most β-lactams
What are the main 2 targets of inhibitors of protein biosynthesis?
- 30S RIBOSOME SUBUNIT - impairs proofreading ability and blocks association with rRNA (Aminoglycosides, Tetracyclines)
- 50S RIBOSOME SUBUNIT - blocks peptide bond formation between amino acids (Chloramphenicol, Macrolides, Lincosamides)
How does the bacterial activity of protein synthesis inhibitors compare?
- 30S RIBOSOME target - Aminoglycosides = bactericidal; Tetracyclines = bacteriostatic
- 50S RIBOSOME target - Florfenicol = bactericidal; Chloramphenicol, Macrolides, Lincosamides = bacteriostatic
How do Aminoglycosides and Tetracyclines compare?
AMINOGLYCOSIDES = bactericidal; irreversibly binds to the 30S ribosome and inhibits the rate of protein synthesis and the fidelity of mRNA translation
TETRACYCLINES = bacteriostatic; reversibly binds to 30S ribosome and prevents the attachment of tRNA to the mRNA complex
What is the main therapeutic use of Aminoglycosides? What is the oldest member of the class?
bactericidal to G- aerobes
Streptomycin - use has declined
What are 3 common Aminoglycosides? What are they used for?
- Gentamicin, Amikacin - controls uterine, skin, respiratory, urinary tract, ear, and eye infections and septicemia
- Neomycin - enteric infections (orally), skin, ear, and eye infections (topical)
- Kanamycin - bacterial enteritis (orally), symptomatic relief of diarrhea
What Aminoglycoside has an expanded spectrum?
Gentamicin and Amikacin —> effective against G+
What next-generation Aminoglycoside is currently in use? How has it been improved?
Plazomicin
lacks nephrotoxic and ototoxic side effects
How does the mechanism of action of Aminoglycosides affect their therapeutic use?
their uptake includes an oxygen-linked energy-dependent step —> only works against aerobic bacteria
How does the chemical structure of Aminoglycosides affect their distribution?
highly polar, poorly lipid soluble
- minimum distribution into the CNS
- accumulates in renal cortex and otic endolymph
- poorly absorbed from GI tract
What causes resistance against Aminoglycosides? What 2 are exceptions?
inactivation of various bacterial enzymes
- Amikacin
- Plazomicin
What 3 adverse effects are commonly caused by Aminoglycosides?
- nephrotoxic
- ototoxic
- neurotoxic (neuromuscular blockade)
What is the therapeutic uses of Tetracyclines?
BROAD SPECTRUM: G- and G+; aerobes and anaerobes + bacteriostatic
