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Tobramycin


- See: aminoglycosides and addition of aminoglyocides to cement

- Discussion:
    - adult dose w/ normal renal F(x) & serious infection: 1mg/kg q8hr;
    - peds: 7.5 mb/kg/day q8hr (Levels: trough <2; peak: 4-8 hr)
    - for life threatening infection may use 1.66mg/kg q8hr (reduce dose as soon as possible);
    - commonly added to cement for treatment of infections; (see: addition of tobra to cement / addition of antibiotics to cement)
    - gent and tobra may have similar antibacterial spectra; however, in vitro a given concetration of tobra is may be twice as effective as
           gent against pseudomonas
           - tobra is more active than gent against pseudomonas, including gent-resistant strains, and is usually indicated over gent for
                      pseudomonas infections, in combination with an antipseudomonal penicillin (AMA, 1983).
    - diffusion from blood into CSF minimal even w/Inflammation;

- Cautions:
    - in patients with impaired renal f(x);
         - give initial loading dose of 1mg/kg;
         - additional doses should be adjusted based on the creatinine clearance;
         - must measure serum levels; use with caution in patients w/ renal failure;
         - avoid other nephrotoxic, ototoxic drugs; Monitor CN VIII F(x);
         - note that advanced age and dehydration increase the risk of toxicity;
         - dosing regimens for patients with renal insufficiency: dose for 70kg adult: gm / dosing interval (hr):
                - >80: 0.10-.14/8; CrCl:50-79:.10-.14/8-12hr;
                - CrCl:30-49:0.10-0.14/12-18hr; CrCl:10-29:: 0.10-0.14/24-36hr;
                - 84-93% of drug will be excreted in to urine (w/ nl RF(x));
         - supplement dose after dialysis:
                - hemo: 1-2 mg/kg
                - CAPD: 3-4 mg/Lit of dialysis
    - neuromuscular blockade; hallucinations;
    - interactions:
         - will interact with cephalothin (nephrotoxicity), Cis platin (nephrotoxicity, ototoxicity)
         - neuromuscular blocking agents (apnea or respiratory paralysis), loop diuretics (ototoxicity), penicilln in RF (decrease
                   aminoglycocans effectiveness) vancomycin (nephrotoxicity), oral anticoagulants (increase PT)


- References for Tobramycin: 

- References for use with Calcium Sulfate Beads:
     - Local and Systemic Levels of Tobramycin Delivered from Calcium Sulfate Bone Graft Substitute Pellets 
     - Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material
     - Effectiveness of commercially-available antibiotic-impregnated implants
     - Antibiotic Beads and Osteomyelitis: Here Today, What's Coming Tomorrow?
     - Antibiotic-impregnated Calcium Sulfate Use in Combat-related Open Fractures
     - In vitro gentamicin release from calcium phosphate bone substitutes influence of carrier type on duration of the release profile 
     - Tobramycin-impregnated Calcium Sulfate Prevents Infection in Contaminated Wounds
     - The treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant
     - USE OF BIODEGRADABLE ANTIBIOTIC BEADS IN ORTHOPAEDIC INFECTIONS
     - Treatment of Infected Hip Arthroplasty with Antibiotic-Impregnated Calcium Hydroxyapatite. 
     - Antimicrobial Bone Graft Substitutes
     - The in vitro elution characteristics of vancomycin from calcium phosphate-calcium sulfate beads. 
     - Locally-administered antibiotics in wounds in a limb
     - Clinical Application of Tobramycin-Impregnated Calcium Sulfate Beads in Six Dogs (2002-2004)
     - In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate 
     - Effectiveness of Local Antibiotic Delivery with an Osteoinductive and Osteoconductive Bone-Graft Substitute

The absence of nephrotoxicity and differential nephrotoxicity between tobramycin and gentamicin.
Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures.
Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients.
Comparative cost effectiveness of gentamicin and tobramycin.
Systematically individualizing tobramycin dosage regimens.

What Is the Role of Antibiotic-Containing Cement in Total Knee Arthroplasty?: Commentary on articles by Robert S. Namba, MD, et al.: “Risk Factors Associated with Deep Surgical Site Infections After Primary Total Knee Arthroplasty. An Analysis of 56,216 Knees,” and Pedro Hinarejos, MD, PhD, et al.: “The Use of Erythromycin and Colistin-Loaded Cement in Total Knee Arthroplasty Does Not Reduce the Incidence of Infection. A Prospective Randomized Study in 3000 Knees”