8.5 Flashcards
What is the difference between ketolides and macrolides?
Ketolides bind to 2 RNA domain vs macrolides bind to only 1.
= kotolides bind tighter, harder to efflux
What are ketolides used for? Spectrum?
Respiratory infections
strep, staph
H. flu, Pertussis
Atypical: Chlamydia, Mycoplasma, and Legionella
What are the toxicities of ketolides?
Erythromycin – GI – N/V/D; Phlebitis
QT prolongation
Erythromycin and Clarithromycin – Cyp 3A4 inhibitors
Blurred vision, diplopia, difficulty focusing
Severe liver damage
What is the mechanism of tetracyclines and Glycylcyclines?
Bind to 30s and prevent protein synthesis
How do bugs become resistant to TCN?
Efflux pumps
Ribosomal mutation
What is the spectrum of TCN?
Strep pneumo, staph aureus
H. flu, Neisseria
Atypical: Rickettsia, Chlamydia, Mycoplasma, Borrelia, Treponema
What TCN is PO and IV?
Doxycycline
What does minocycline treat?
MRSA
Leprosy
How are Glycylcyclines different than TCNs?
Glycl amide group- prevents recognition by efflux pump
What is the coverage of glycylcyclines?
G+: Strep, Staph (including MRSA), Enterococci (including VRE)
G-: H. Flu, Neisseria, Enterobacteriacea
Anarobes: B. fragilis and many other
Atypical: Mycoplasma
What are the toxicities of TCNs?
Rings structure – a potent chelator of metal ions gray to yellow discoloration of growing teeth and bone Contraindicated for pregnant women Cautious for children <8y.o Rashes, anaphylaxis Blue-black hyperpigmentation – minocycline Photosensitivity N/V Hepatoxicity
What is the mechanism of Choramphenicol?
Binds to 50s, blocks formation of peptide bonds
If a bug is resistant to Choramphenicol, what else is it likely resistant to?
also resistant to macrolides/ketolides, clindamycin ***
**These drugs are all similar, if resistant to one, likeley resistant to all
How do bugs become resistant to Choramphenicol?
Producing enz acetylates chloramphenicol prevent binding to target
Efflux pumps
What is the spectrum of chloramphenicol?
Strep
H. Flu, Neisseria, Salmonella, Shigella
**Anaerobes – B fragilis and other
**Atypical – Mycoplasma, Chlamydia, Rickettsia
What are the toxicities of chloramphenicol?
Reversible bone marrow suppression – dose dependent
Bind to mitochondrial ribosome
Irreversible aplastic anemia – occurs after completion a of therapy
Neonates – caused “gray baby syndrome”
Not fully functional liver enz (i.e UDP-glucuronyl transferase) accumulation of unmetabolized chloramphenicol
Optic neuritis
What is the mechanism of clindamycin?
Binds to 50s, inhibits protein synthesis
Similar to macrolides
If a bug is resistant to clindamycin, what else is it likely resistant to?
macrolides
What is the spectrum of clindamycin?
G+: Strep, staph
Anaerobes: B. Fragilis, Clostridium, and most other
**Most G- intrinsically resistant
What are the toxicities of clindamycin?
Induce C diff colitis – 0.01 -10%
Diarrhea
Rashes
What is the mechanism of Streptogramins?
2 different macrocyclic compounds
Binds to 50S prevent protein synthesis
Each compound has moderate antibacterial effects
Dalfopristin binds to ribosome -> induce conformational change -> enhance binding of quinupristin
What other Abx binding sites do streptogramins overlap with?
Macrolides
Clindamycin
What is the coverage of streptogramins?
Covers G+ only (i.e. strep, staph, and enterococcus)
What are the toxicities of streptogramins?
CYP450 inhibitor
Phlebitis – should be given via central line
Arthralgia, myalgias
Hyperbilirubinemia
What is the mechanism of linezolid?
Prevents 30s from joining with 50s= ribosome can’t form
How do bugs become resistant to linezolid?
Mutation of ribosome
Efflux pumps
What is the spectrum of linezolid?
G(+) – strep, staph including MRSA and VRE
When is linezolid used? How dosed?
Reserved for VRE, MRSA
PO/IV = bioavalibility
What are the toxicities of linezolid?
N/V/D Thrombocytopenia Anemia, leukopenia – reversible Not be given with MAO inhibitors Together with SSRI serotonin syndrome
What is the spectrum for nitrofuratonin/macrobid?
Staph enterococcus
UTI only, need good renal fxn
What are the toxicities of nitrofuratonin/macrobid?
N/V, rash, interstitial pneumonitis, hepatitis, hemolytic anemia, and neuropathy
