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Aminoglycosides
Mainstays for therapy of serious G- infections (usually in combo w/ another agent)
Aminoglycosides MOA
Binds outer G- membrane, rearranges LPS
-into cytoplasm via energy dependent mechanism and now trapped
-binds 30s and 50s subunits
-↓ protein synthesis ↑ mRNA misreads

Bactericidal (counterintuitive)

Has post antibiotic effect
Aminoglycosides PKS
Poorly absorbed GI
Lung concentration 25%-50% serum

Excretion primarily via glomerular filtration, mostly unchanged

Mind alterations in patient Vd & Ke
-elderly, critically ill, renal disease

Aminoglycoside adverse effects
Watch for nephrotoxicity and ototoxicity

Can cause thrombophlebitis 
Aminoglycoside spectrum of activity (SOA)
Mostly G- including SPACE

Will cover staph/enterococcus
-only used in synergy for G+
Aminoglycoside indications
SERIOUS G- infections
-i.e.:
Bacteremias, intra-abdominal infections, lower respiratory, bone/joint, complicated UTI

Use Gentamycin, Tobramycin, Amikacin
Streptomycin/Gentamycin specfic uses:
Streptamycin reserved for Tuberculosis

Gentamycin for Brucellosis
Oral Aminoglycosides
Elective colorectal surgery prophylaxis or Hepatic coma
-Neomycin

Intestinal amebiasis/tapeworm
-Paromomycin
Aminoglycoside dosing guidelines
Narrow theraputic window

Follow pharmacokinetic principles
-most accurate
-lowest toxicity + lowest failure rates

Avoid trial and error
-less accurate
-higher tox, higher failure

Order peak/trough after 3rd dose
-again after any dose adjustment or kidney function alterations
Once-daily aminoglycosides
Based on post antibiotic effect

-trough allowed to fall below MIC
-allows kidneys to process drug
-↓ nephrotoxicity
Topical Aminoglycosides
Ophtalmic solution
-gent/tobra/neo combo

Gentamycin topical preparation

Wound irrigation
-gent/tobra/kana solution
Vancomycin MOA
Glycopeptide antibiotic seeing resurgence  due to increase in MRSA

Inhibits polymerization of d-ala dimers into growing peptidoglycan chain

Bactericial when organisms mulitplying

Has post antiobiotic effect
Vancomycin PKS
Poor GI absorbtion
-given IV except for C. Diff

Distributes to CSF only with inflammation

Excretion via glomerular filtration, mostly unchanged

Mind Vd & Ke altered patients

*NOT removed in dialysis*
Vancomycin adverse effects
New preparations well tolerated
-old mississipi mud not so well

*Unique side effect*
Red Man Syndrome
-histamine like reaction
-erythematous macular rash from upper chest through head
Vancomycin SOA
G+ but NO G-

Will cover some big resistant bugs
-MRSA, MRSE

Won't cover Vancomycin Resistant Enterococcus (VRE)
Vancomycin special indications
CDC has developed special guidelines for Vanco out of fear of resistance

1. Use for serious G+ B-lactam resistant organism
2. Serious B-lactam allergy (includes surgical prophylaxis)

3. Serious C.Diff colitis

4. Prosthesis surgery prophylaxis at compromised institutions

5. Surgical prophylaxis if high risk for endocarditis
When should Vancomycin be discouraged...
1. Routine surgical prophylaxis
2. Emperic therapy
3. C. Diff primary treatment in non-life threatening cases
4. Dosing convenience eventhough organism is B-lactam sensitive
Vancomycin dosing guidelines
Follow pharmacokinetics

Nomograms acceptable for initial dosing

Peak/trough at 3rd dose
-again w/ dose change, renal function change
Quinupristin/Dalfopristin
Synercid®
Combo 30/70

Bind 50s ribosome
Bactericidal together

Gets many resistant G+
-VRE feacium covered but not VRE faecalis
Linezolid
Inhibits protein syntheis by binding 23s & 50s

Also gets many resistant G+

*Can MAO inhibit*
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