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Gentamicin/Garamycin


- See: Aminoglycocides

- Discussion:
    - indicated for serious Gm Neg infections caused by suseptable Pseudomonas, Proteus,  E. coli, Klebsiella, Enterobacter sp., Serratia, and Gm Neg Sepsis;
    - as with all aminoglycocides, gentamicin binds to bacterial ribosomes and inhibits protein synthesis;
    - tobramycin is more active than gentamicin against Pseudomonas, including gentamicin-resistant strains, and is usually indicated over gentamicin for pseudomonas infections, in combination with an antipseudomonal penicillin (AMA, 1983).
     - reference:
           - Aminoglycoside therapy. Current use and future prospects.


- Dosage:
    - base dosage on Renal function and serum; 3-5 mg/kg/day in 3 divided doses / 24-36 hrs, or 1.5mg/8hrs - Loading Dose 2mg/kg;
    - usual dose for serious infections is 1 mg/kg q 8 hrs;
    - dose for Life Threatening Infections: 1.7 mg/kg q 8hr (reduce ASAP)
    -  peak: 5-8 ug/ml; trough: 1-2 ug/ml;
    - w/ osteomyelitis
          Dose        time p admin.  Mean Ser conc (ug/ml)    Mean Bone conc (ug/gm)
           1.7 mg/kg/8hr IM  120-60         3.7-6.0                   3.66
    - references:
           - Gentamicin volume of distribution in critically ill septic patients.
           - Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function.
           - Increased burn patient survival with individualized dosages of gentamicin.
           - Kinetic model for gentamicin dosing with the use of individual patient parameters.
           - Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients.
           - Bactericidal activity of gentamicin against S. aureus. In vitro study questions value of prolonged high concentrations.
           - Gentamicin pharmacokinetics in 1,640 patients: method for control of serum concentrations.
    - peds: 7.5 mg/kg/day q8hr (levels: trough < 2, peak:4-8)
            - Gentamicin in neonates: the need for loading doses.


Role of Gentamicin in Bone Cement:
    - addition of antibiotics to bone cement
    - osteomyelitis
    - references:
           - Release of gentamicin from acrylic bone cement. Elution and diffusion studies.
           - Role of gentamicin-impregnated cement in total joint arthroplasty.
           - Prophylaxis with systemic antibiotics versus gentamicin bone cement in total hip arthroplasty. A five-year survey of 1688 hips.

Local Antibiotics:
      -
Locally administered antibiotics for prophylaxis against surgical wound infection. An in vivo study.


- Complications:
   - renal failure: (Gentamicin in Renal Failure)
          - note nephrotoxicity, ototoxicity, decrease dose with renal failure;
          - parental aminoglycosides: Will interact with cephalothin  (nephrotoxicity), Cis platin (nephrotoxicity,ototoxicity)
          - ether and neuromuscular blocking agents (apnea or respiratory paralysis), loop diuretics, (ototoxicity), Pen in RF
          - decreased aminoglyc effectiveness) vancomycin (nephrotoxicity),  oral anticoagulants (Increase PT);
          - dosing Regimens for Patients with Renal Insufficiency:  (Dose for 70 kg Adult (gm/dosing interval in hours):
          - CrCl: >80: = 0.10-0.14/8; CrCl: 50-79 = 0.10-0.14/12-18;;
          - CrCl:30-49 = 0.10-0.14/12-18;; CrCl::10-29 = 0.10-0.14/24-36;;
          - 70% of drug will be excreted in to urine (w/ nl RF(x))
    - references:
          - Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients.
          - The absence of nephrotoxicity and differential nephrotoxicity between tobramycin and gentamicin.


Misc:
    - diffusion from Blood into CSF minimaleven w/Inflammation;
    - note: ratio of CSF to blood level (%): normal meninges: nil; inflammed meninges: 10-30