LEC 36 Antimicrobials IV Flashcards
What is the DOC for MRSA?
Vancomycin
What clinical resistance is associated with vancomycin?
- Enterococcal Resistance (VRE)
- Enterococus faecium
However: Enterococcus faecalis is 100% suseptible to Vancomycin
What are the pharmacokinetics of vancomycin?
- No absorption from GI tract - IV only
- t1/2 = 6 hrs
- Penetrates CSF when meninges inflamed
- Eliminated by kidney (glomerular)
What are the adverse effects associated with vancomycin?
- Hypersensitivities
- Rapid IV injection - “vancomycin infusion reaction” - tx with benadryl and slow the infusion
- Nephrotoxicity - less than aminoglycosides
What are the pharmacokinetics of beta lactams?
- Food adsorbs penicillins - decreases F
- Poor penetration into CSF (unless meninges inflamed) and prostate
- Little to no liver metabolism - some ceph’s do liver metab and biliary excretion
- Kidney elimination - t1/2 = 30-90 mins - Probenecid can compete and extend half life of drug
Which penicillinase-resistant penicillins are the DOC for susceptible strains of Staph aureus?
Nafcillin (IV/IM) or Oxacillin (oral)
“think staph… think naf”
What are the adverse effects of penicillins?
- Hypersensitivities - rash (mild or severe - Stevens-Johnson syndrome), fever, serum sickness, anaphylaxis
- Impaired platelet function (rare)
- CNS toxicity - seizures if not dosed for CrCl
- Alterations in normal microflora
How do beta lactams cause hypersensitivity rxns?
- Beta-lactam rings bind amino groups on proteins
- Antibodies recognize this compound as a hapten-protein complex and creates an immune response to the drug
Essentially creates a hapten-protein complex vaccine
What is different about cephalosporin metabolism compared to penicillins?
- Many cephalosporins have longer half lives than penicillins
- Some cephalosporins are metabolized by the liver by deacetylation
What is the spectrum of coverage of first gen cephalosporins?
- Gram Positive cocci (Strep & Staph, but not MRSA or MRSE)
- Gram Negative organisms: Proteus, E. coli, Klebsiella pneumoniae
Mnemonic: SS PEcK
Cephalexin is what generation cephalosporin?
First Generation
Given PO; Cefadroxil has better oral absorption and BID dosing
What is the spectrum of activity of the second generation cephalosporins?
- Reduced gram positive compared to first gen
- Increased gram neg compared to first gen: H. influenzae, Enterobacteriaceae, Neisseria (gonorrhoeae, meningitidis), P. mirabilis, E. coli, K. pneumoniae, Serratia
Mnemonic: HENPEcKS
Which two second generation cephalosporin drugs are effective against anaerobes?
Cefoxitin and Cefotetan
What is the spectrum of activity of third gen cephalosporins?
- reduced gram positive
- Increased gram neg:
- H. influenzae
- Enterobacteriaceae
- Neisseria
- P. mirabilis
- E. coli
- K. pneumoniae
- M. catarrhalis
- Better activity against Enterobacter
Mnemonic: HENPEcK ME
What is the DOC for Neisseria (gonorrheae, meningitidis) infxn?
Ceftriaxone
Which two 3rd gen cephalosporins are active against P. aeruginosa?
Cefoperazone and Ceftazidime
What are the adverse effects of cephalosporins?
- Hypersensitivities
- some nephrotoxicity
What is the spectrum of activity of fluoroquinilones?
- more potent against gram neg
- more active against gram pos
- more active against intracellular organisms
- poor activity against anaerobes (not for pus)
What are the pharmacokinetics of fluoroquinilones?
- Most are well absorbed orally - good for IV to PO switch
- Chelators of divalent cations (Ca or Mg) - decrease absorption
- Widely distributed in body
- Elimination varies by drug
What are the adverse effects of fluoroquinolones?
- GI upset - N/V, abdominal discomfort
- Hypo/Hyperglycemia
- Photosensitivity
- CNS: GABA inhibition, HA, dizziness, insomnia
- Connective tissue - tendon rupture; do not use in kids & pregnant women
Which two fluoroquinolones are the “respiratory quinolones”?
Moxifloxacin and Levofloxacin
Ciprofloxacin is used to treat what?
Anthrax
2nd gen fluoroquinolone
Aminoglycosides target what kind of bacteria?
Gram negative
What is the DOC for VRE?
Vancomycin resistant enterococcus
Aminoglycoside + Beta-lactam
They are synergistic
Describe the synergistic relationship of aminoglycosides and beta lactams when treating Enterococcus.
- The beta lactam helps break down the cell wall
- This helps the aminoglycoside penetrate the cell to reach its target (30S)
What are the pharmacokinetics of aminoglycosides?
- Renal elimination - t1/2 = 2-3 hours
- t1/2 from tissues (renal & inner ear) = 30-700hrs
- half life longer in pts with little or no renal function
- At high concentrations - can disrupt cell membrane and can inhibit mitochondria
What toxicities are associated with aminoglycosides?
- Cochlear and Vestibular (Ototoxicity)
- Nephrotoxicity
Hearing loss and vertigo type stuff
Which aminoglycoside has the highest risk of nephrotoxicity?
Neomycin
Which aminoglycoside has the lowest risk of nephrotoxicity?
Streptomycin
Tetracyclines are the drug of choice for which infections?
- Rickettsiae (Rocky Mt. Spotted Fever)
- Chamydiae
- Borrelia (Lyme)
- Mycoplasma pneumoniae
useful against: H. pylori, Propionibacterium acnes, Treponema (syphilis)
What are the adverse effects of tetracyclines?
- GI - irritation/diarrhea; superinfection (pseudomembranous colitis)
- Photosensitivity
What are the adverse effects of macrolides?
- GI - “gastric prokinetic activity”
- Cholestatic jaundice
- Cardio - prolonged QTc interval
Which drug is commonly given to children to treat constipation?
Erythromycin
Which two drug classes cause prolonged QTc intervals?
- Macrolides
- Fluoroquinolones
