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RavLect14: AGs

Aminoglycosides

QuestionAnswer
Aminoglycosides Gentamicin Tobramycin Amikacin Streptomycin Neomycin (only used topically)
AG MoA IRREVERSIBLY bind to bacterial ribosome 30S to inhibit protein synthesis Ionic interactions w/ cell wall; mostly CIDAL
AG disadvantage Renal toxicity; must monitor SCr daily against BUN (big hassle!)
AG PK (linear) Concentration Dependent w/ Post-ABx effect 1-compt model; H2O distribution Standard dose = multi-dose vs Once-daily dosing = big dose (safer for kidneys) Do NOT distribute into pus, abscess, & fatty tissue (poor for anaerobic Tx) Poor CNS di
Formulas for AG dosing T ½ = 0.693/Kd Vd = 0.25L/Kg (use adjusted BW if obese) Kd(hr –1 ) = Cl (L/hr)/VD (L) LD (loading dose) = (desired AG serum conc.)CPss*(VD
Cockcroft-Gault formula for eGFR [(140-age)*(kg)*(0.85 if female)]/[72*Scr] ml/min -> liters/h: multiply by 0.06 to put into Kd eqn
AG SoA Combo synergistic therapy, except in kidneys/urine G-: SPACE M. tuberculosis Mycobacterium Avium- intracellular MAI or MAC G+: Enterococci, Streptococci, Staphylococci, Listeria Do NOT cover strict anaerobes (B. frag) without facilitation.
AG ADRs 1) Nephrotoxicity (ATN-acute tubular necrosis, Fanconi's syndrome-casts w/ nonoliguria) 2) Otoxicity (Hearing, vestibular balance problems -> N&V) be careful with Platinum agents and Vinca alkaloids 3) Neuromuscular blockage 4) DDI w/ PCN; Don't
AG Combos (good against anaerobes & harder for resistance to develop b/c different MoA) start as empiric therapy, then drop the AG drug b/c it works slower than the other b-lactam drugs w/ b-lactams (PCN or Amp) for Enterococcus- gent preferred. If resistanct, use w/ vancomycin or linezolid w/ vanco & rifampin for coag (-) staph endocarditis. w/ antistaph PCN for S. aureus endocarditis Listeria: Gent+Amp is 1st line (2nd line: Sep
Clinical Use of AGs Gram (-) Nosocomial (hospital/ventilator associated) pneumonia, bacteremia, pyelonephritis, urosepsis, sepsis serious polymicrobial infections
Conventional or Multiple dose (Standard Dose) Urinary, Tissue, Lung/blood respectively: 1(synergistic dose), 1.5, 2mg/kg for Gent & Tobramcyin 5, 6, 7 mg/kg for Amikacin
Standard Dose Levels, time to gather Drug Levels: Usually obtained after the 3rd dose Peak: obtain 30 min after a 30 min infusion or 15 mins after 60 min infusion Trough: just prior to the 4th dose
Standard Dose: Gent/Tobra Peaks & Troughs Peaks: Urinary tract infections 3-5 mcg/ml Skin & soft tissue infection 5-7 mcg/ml Pneumonia & sepsis 7-10 mcg/ml Trough: <2 mcg/ml
Standard Dose: Amikacin Peaks & Troughs Peaks: Urinary tract infections 25 mcg/ml Skin & soft tissue infection 30 mcg/ml Pneumonia & sepsis 35 mcg/ml Trough: <10 mcg/ml
Peak & Trough problem? Too high peak will harm ears Too high trough will harm kidneys
Once Daily (High Dose, Single Dose, or Extended Interval Dosing) Gent/Tobra: 7mg/kg Amika: 15 mg/kg for peak of about 20mcg/ml or 60mcg/ml Based on actual body weight unless >20% IBW then use an adjusted weight Check random level after the 1st dose between 6-14 hr. NOT a trough/peak.
Once Daily Dosing Interval CrCl 60 ml/min: Q24H CrCl 40-59 ml/min: Q36H CrCl 20-39 ml/min: Q48H CrCl <20 ml/min: monitor serial levels Follow Hartford protocol! Out of bounds, stop drug!
When to NOT use once daily dosing? Enterococcal endocarditis Pregnancy Select Pediatric Populations Cystic fibrosis Burns Renal failure (CrCl<10)
Synergy doses Do NOT require levels but UTI infection dosing at 1mg/kg requires levels to assure efficacy
AG drug comparisons G- (SPACE): Tobramycin>Gent (Amikacin most potent, but very restricted use b/c toxic). Needs combo for anaerobic B. frag. G+: Gent has best activity. Combine w/ b-lactams for Entercoccus, Strep, Staph, and Listeria.
Created by: cheeoh
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