Aminoglycosides Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology

Aminoglycosides are aminocyclitol derivatives with concentration-dependent bactericidal activity against Gram-negative aerobic bacteria by binding to the 30S and 50S ribosomal subunit interface. Anaerobic bacteria are resistant due to oxygen-dependent transport. Dibasic cations (e.g., magnesium, calcium) and acidic conditions reduce efficacy. Streptomycin and kanamycin have limited activity against some Gram-negatives, especially P. aeruginosa. Gram-positive organisms (e.g., streptococci) are relatively resistant but can be synergistically inhibited with penicillins or vancomycin. Aminoglycosides exhibit a postantibiotic effect, allowing less frequent dosing. Resistance occurs via plasmid-mediated enzymatic modification or reduced uptake.

Administration and Adult Dosage

- IM or IV: Slow intermittent infusion over 30–60 min (15-min infusions safe). Once-daily regimens combine daily dose into a single 60-min IV infusion to leverage concentration-dependent bactericidal and postantibiotic effects, potentially reducing toxicity
- IT or intraventricular: Required for therapeutic CSF levels
- See Aminoglycosides Comparison Chart for specific agents (e.g., gentamicin, tobramycin, amikacin, netilmicin, streptomycin)

Special Populations - Pediatric Dosage

Refer to Aminoglycosides Comparison Chart for specific agents.

Special Populations - Geriatric Dosage

Same as adult dosage, adjusted for age-related renal function decline.

Other Conditions

- Use ideal body weight (IBW) for mg/kg dosing; for morbid obesity, use dosing weight: IBW + 0.4 × (TBW − IBW)
- Conventional dosing: Target serum levels 3–10 mg/L; peaks >6 mg/L (gentamicin/tobramycin) may improve outcomes in bacteremia/pneumonia
- Once-daily dosing: Target higher peaks (>10–20 mg/L for gentamicin/tobramycin) based on disease state/pharmacokinetics
- Renal impairment (initial dosage guidelines):
1. Select loading dose (mg/kg, IBW or dosing weight):
- Tobramycin/Gentamicin: 1–2 mg/kg (peak 3–10 mg/L)
- Amikacin: 5–7.5 mg/kg (peak 15–30 mg/L)
2. Maintenance dose (% of loading dose) based on corrected Clcr and dosing interval (8, 12, or 24 hr):

Clcr (mL/min)	t½ (hr)	8 hr (%)	12 hr (%)	24 hr (%)
90	3.1	84	—	—
80	3.4	80	91	—
70	3.9	76	88	—
60	4.5	71	84	—
50	5.3	65	79	—
40	6.5	57	72	92
30	8.4	48	63	86
25	9.9	43	57	81
20	11.9	37	50	75
17	13.6	33	46	70
15	15.1	31	42	67
12	17.9	27	37	61
10	20.4	24	34	56
7	25.9	19	28	47
5	31.5	16	23	41
2	46.8	11	16	30
0	69.3	8	11	21

Alternatively, give 50% of loading dose at interval ~estimated t½. For Clcr <10 mL/min, use measured serum levels; give 50–75% of loading dose post-hemodialysis
- Critically ill patients (e.g., cystic fibrosis, burns, major surgery) have variable pharmacokinetics, requiring individualized dosing

Dosage Forms

Refer to Aminoglycosides Comparison Chart for specific agents.

Patient Instructions

- Report dizziness, ringing, or fullness in the ears to your physician immediately

Pharmacokinetics - Fate

- Absorption: Poor oral/rectal (0.2–2%); ~5% across denuded skin; IM/IV infusion (30–60 min) yields complete absorption, peak levels in 0.5–1.5 hr
- Protein Binding: Low
- Distribution: Vd ~0.3 ± 0.08 L/kg, increased in fever, edema, ascites, fluid overload, neonates; high renal cortex accumulation, reduced with less frequent dosing
- Penetration: CSF ≤25% of serum levels (higher in neonatal meningitis); poor in eye, lung, sputum; adequate in peritoneal cavity with peritonitis
- Elimination: Glomerular filtration of unchanged drug; Cl ~90% of Clcr; low urinary levels persist days post-discontinuation due to tissue egress

Pharmacokinetics - t¹⁄₂

- α phase: 5–15 min
- β phase: ~2 ± 0.4 hr (normal renal function); 1.5–9 hr (neonates <1 week); 3 hr (older infants); 50–70 hr (anuria); variable in obstetric/burn patients
- γ phase: 60–350 hr (typically 150–200 hr), reflecting deep tissue egress; contributes to gradual serum level rise with continued therapy

Adverse Reactions & Side Effects

- Nephrotoxicity: Mild, reversible (5–30% incidence); elevated Crs, BUN, tubular casts/enzymes, β2-microglobulin; rare progression to severe renal disease
    • Risk factors: Long therapy duration, prior aminoglycoside use, advanced age, pre-existing renal/liver disease, volume depletion, female sex, nephrotoxic drugs
- Ototoxicity:
    • Vestibular: Occasional, often permanent (streptomycin); subclinical in ≥40% patients
    • Cochlear: Early damage detectable only by audiometry; conversational frequency loss indicates advanced impairment
    • Risk factors: Therapy duration, bacteremia, hypovolemia, fever, liver disease
- Other: Magnesium/mineral depletion (renal excretion); rare neuromuscular blockade with respiratory failure (in predisposed patients)
- Oral neomycin: Sprue-like malabsorption syndrome

Contraindications

- Hypersensitivity to aminoglycosides

Precautions & Warnings

- Use cautiously in pregnancy, pre-existing renal impairment, vestibular/cochlear impairment, myasthenia gravis, hypocalcemia, postoperative/neuromuscular transmission disorders

Drug Interactions

- Nephro-/ototoxic drugs increase toxicity risk
- Neuromuscular blockers potentiate blockade, risking respiratory paralysis
- Oral neomycin potentiates oral anticoagulants by reducing vitamin K absorption/synthesis
- Ticarcillin/acylampicillins degrade aminoglycosides in vitro (artificially low levels); in vivo degradation in renal insufficiency; amikacin least susceptible

Parameters to Monitor

- Renal function (Crs, BUN) before therapy and every 2–3 days during
- Audiometry/electronystagmography in cooperative patients
- Serum levels:
    • Conventional therapy: Monitor after steady state
    • Once-daily: After first dose, follow-up if renal function changes
    • Neonates/rapidly changing renal function: Initially and every 2–3 days until stable
    • High-risk (elderly, renal impairment, unstable, high peaks, >10 days therapy): Monitor closely
    • Troughs often undetectable in once-/twice-daily dosing; alternative sampling strategies needed

Class and Drug Brand Names

- Class: Aminoglycosides
- Brand Names: Gentamicin (Garamycin), Tobramycin (Nebcin), Amikacin (Amikin), Netilmicin (Netromycin), Streptomycin, Neomycin, Kanamycin

Notes

- Clinically useful: Gentamicin, tobramycin, netilmicin, amikacin
- Streptomycin: Restricted to enterococcal endocarditis (with ampicillin), tuberculosis, brucellosis, plague, tularemia; available only for compassionate use
- Amikacin: Used in Mycobacterium avium complex treatment; lowest resistance among Gram-negatives
- Neomycin: Highly toxic parenterally; used orally for gut sterilization, topically for minor infections
- Kanamycin: Systemic use limited by resistance
- Tobramycin: 2–4× more active than gentamicin against P. aeruginosa; often active against gentamicin-resistant strains; superior peak-to-MIC ratio

References

Hand of Clinical Drug Data