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Paul A. Pham Pharm.D. and John G. Bartlett M.D.
12-18-2009
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Available formulation in Zambia: Solution (eye drops): 0.3% (sulfate). Injection: 10mg; 40 mg per 2ml vial.
- In combination with a penicillin or cephalosporin, aminoglycosides are generally recommended for the initial management of life-threatening infections likely to be caused by Gram- negative organisms (e.g. septicaemia).
- Acute pyelonephritis: Gentamicin 5mg/kg/day then switch to ciprofloxacin 500 mg PO q12h x 7 days when pt can tolerate PO.
Zambia Information Author: Paul A. Pham, Pharm. D.
- Serious infections caused by susceptible strains of organism. With the exception of uncomplicated UTI, aminoglycosides are generally used in combination.
- Bacterial septicemia, including neonatal sepsis
- Skin, bone and soft tissue infections (including burns)
- Meningitis (poor penetration)
- Urinary tract
- Respiratory tract (poor penetration)
- Gastrointestinal tract (including peritonitis) 8) Inflammatory ocular conditions that are steroid-responsive (opthalmic ointment and suspension)
- Pneumonia, hospital-acquired(in combination with a beta-lactam, beta-lactam/beta-lactamase inhibitor, or a 3rd/4th generation cephalosporin)
- Intra-abdominal infection (in combination with an agent with gram-positive and anaerobe coverage)
- Enterococcal endocarditis (in combination with ampicillin)
- Pelvic Inflammatory Disease (PID) (in combination with clindamycin)
- Pseudomonad infections (in combination with a beta-lactam, beta-lactam/beta-lactamase inhibitor, or a 3rd/4th generation cephalosporin)
- Brucella Species
brand
name
| generic
| Mfg
| brand
forms
| cost*
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| Gentamicin | Gentamicin sulfate | ~Various generic manufacturers | IV
vial
10mg/ml (2ml) | $5.00 per vial |
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| IV
vial
40mg/ml (2ml) | $0.90 per vial |
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| topical
cre
0.1% (15g) | $360 |
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| topical
cre
0.1% (30g) | $4.90 |
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| topical
oint
0.1% (15g) | $3.60 |
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| topical
oint
0.1% (30g) | $4.90 |
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| topical
oph gtt
3mg/mL (5mL) | $8.17 |
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| topical
oph gtt
3mg/mL (15mL) | $10.78 |
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| topical
oph oint
0.3% (3.5g) | $19.67 |
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| topical
oph gtt
0.3% (5mL) | $9.54 |
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*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
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Once daily dosing:: 5-7mg/kg IV. Therapeutic drug monitoring generally not recommended. Consider trough in patients at risk for nephrotoxicity (ICU pts, elderly, and concomitant nephrotoxin). Target trough <1 mcg/ml. Don't use Once-daily dosing in pts w/ unstable renal fxn, CrCl <60ml/min, endocarditis, meningitis, or increased Vd (pregnancy, ascites, edema).
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Traditional dosing (mild-moderate infections): 2mg/kg load, then 1.7-2 mg/kg IV q8h (goal peak >6 mcg/ml and trough <2mcg/ml).
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Traditional dosing (severe infections, e.g. Pseudomonas, pneumonia): 3 mg/kg load, then 2mg/kg IV q8h (goal peak >8 mcg/ml and trough <2 mcg/ml).
- Synergy w/ beta-lactams for Gram-positive infections: 1mg/kg IV q8h (goal peak 3-5 mcg/ml). 3 mg/kg once daily synergy dosing may be considered for S. bovis or viridans streptococci (MIC <0.5 mcg/mL only).
- Consider a higher loading dose and obtain a peak and trough after first dose in severe infections (+/- diffuse edema, ascites, shock, burns, CF, and pregnancy) in order to calculate patient-specific pharmacokinetic dose. Doses need to be adjusted based on changing renal function and/or volume status.
- Trough should be obtained (generally after 3rd dose) immediately before next dose.
- Peak should be obtained 30 mins after the end of a 30 mins infusion (generally after 3rd dose) .
- For obese patients: use calculated lean body weight plus 40% of excess fat (Dosing Body Weight (DBW) = Ideal Body Weight (IBW) + 0.4 (actual body weight-IBW).
- IBW= 50kg (for males) OR 45.5kg (for females) PLUS (2.3 x inches over 5ft).
- Intraventricular or intrathecal administration: preservative free gentamicin 5 mg q24h (range 4-10 mg).
Standard loading dose for all levels of renal function. GRF>70 ml/min: Use standard dose. GFR 50-69 ml/min: calculated GFR x 0.045 = "mg/kg" q12h (Ex. for GFR 56 ml/min: 56 x 0.045 = "2.5" mg/kg q12h. Monitor peak and trough.
Standard loading dose for all levels of renal function. GFR 40-49 ml/min: calculated GFR x 0.045 = "mg/kg" q12h (Ex. for GFR 45 ml/min: 45 x 0.045 = "2" mg/kg q12h). GFR 20-39: calculated GFR x 0.09 = "mg/kg" q24h. Monitor peak and trough.
Standard loading dose for all levels of renal function. GFR <20 ml/min: 2-2.5 mg/kg x 1, then redose when level <2 mcg/mL. . Monitor peak and trough.
Standard loading dose, then 1.7-2 mg/kg post-HD (treatment doses) or 1.0 mg/kg post-HD (for synergy). Peak (measure 2 hours-post dose, target 7-10 mcg/mL) and trough (before next HD session, depending on residual renal function, expect 3-5 mcg/mL.)
2-4 mg per Liter of dialysate exchange per day. Aminoglycosides given for prolonged periods to patients receiving continuous peritoneal dialysis have been associated with high rates of ototoxicity.
CVVH or CVVHD: loading dose 3 mg/kg, then 2mg/kg q24-48 (measure peak 2 hours-post dose, target 7-10 mcg/mL). Check a 24-h concentration (redose <2 mcg/mL).
- Renal failure (usually reversible). Risk factors: older patients, preexisting renal and hepatic disease, volume depletion, traditional Q8h dosing, large doses, concomitant nephrotoxic drug (including vancomycin ), use of gentamicin, and length of therapy (most important). Controversial but trough may be associated with nephrotoxicity.
- Irreversible vestibular toxicity (4-6%). Most patient compensate with visual and proprioceptive cues. Monitor for nausea, vomiting, nystagmus and vertigo (exacerbated in the dark).
- Irreversible cochlear toxicity (3-14%). Risk factors: repeated exposure (cumulative dose and duration of therapy), genetic predisposition, renal impairment, specific aminoglycoside (neomycin>streptomycin>gentamicin>tobramycin>amikacin>netilmicin), elderly, age, bacteremia, hypovolemia, degree of temp elevation and liver dysfunction (JID 1984:149:23-30). 62% of hearing lost were at frequency above 9kHz (high pitch) at a mean of 9 days of therapy (JID 1992; 165:1026-1032).
- Genetic predisposition in some cases vestibular and cochlear toxicity. Check family Hx for aminoglycoside ototoxicity.
- Monitor for ototoxicity in any patients receiving >3 days of aminoglycoside. Vestibular toxicity monitoring: check baseline visual acuity using a Snellen pocket card. After 3 days of aminoglycoside, have patient shake head (side to side) while reading a line. Early sign of otoxicity if patient loses 2 lines of visual acuity. Check Romberg sign. Cochlear toxicity monitoring: audiology test.
- Neuromuscular blockade (esp with myasthenia or Parkinsons and rapid infusion of large aminoglycoside doses)
- Allergic reaction (secondary to sulfites in some formulations)
- Cephalothin: increased risk of nephrotoxicity.
- Loop diuretics (bumetanide, furosemide, ethacrynic acid, torsemide):cochlear toxicity (esp. w/ ethacrynic acid). Avoid co-administration.
- Nondepolarizing musclerelaxants (atracurium, pancuronium, tubocurarine, gallamine triethiodide): possible enhanced action of nondepolarizing muscle relaxant resulting in possible respiratory depression.
- Other nephrotoxic agents (e.g.,amphotericin B , foscarnet , cidofovir , and IV contrast dyes): additive nephrotoxicity. Avoid co-administration.
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Penicillins:in vitro inactivation. Do not mix or run in the same tubing.
- Vancomycin: increased risk of nephrotoxicity.
- MIC breakpoint for Enterobacteriaceae and Gram-negative non-lactose fermenters including P. aeruginosais 4 mcg/mL.
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Enterococci synergy with ampicillin if MIC <500 mcg/mL. If >500 mcg/mL to gentamicin, test for streptomycin sensitivity.
Enterococcal endocarditis andtularemiamay be among the few infections in which gentamicin have a clearly defined role. Gentamicin appears more nephrotoxic but less ototoxic than tobramycin. Monitor renal function and watch for ototoxicity (auditory and vestibular). Don't use once daily dosing in pts w/ unstable renal fxn, CrCl <60ml/min, endocarditis, meningitis, or increased Vd (eg pregnancy, ascites, edema).
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