Indications
Amikacin, gentamicin, and tobramycin: Treatment
of serious gram-negative bacterial infections and infections
caused by staphylococci when penicillins or other
less toxic drugs are contraindicated. Streptomycin: In
combination with other agents in the management of
active tuberculosis. Neomycin: Used orally to prepare
the GI tract for surgery, to decrease the number of ammonia-
producing bacteria in the gut as part of the management
of hepatic encephalopathy, and to treat diarrhea
caused by Escherichia coli. Tobramycin by inhalation: Management of Pseudomonas aerugi- A
nosa in cystic fibrosis patients. Gentamicin, streptomycin:
In combination with other agents in the management
of serious enterococcal infections.
Gentamicin IV: Prevention of infective endocarditis.
Gentamicin (topical): Treatment of localized infections
caused by susceptible organisms. Unlabeled
Use: Amikacin: In combination with other agents in
the management of Mycobacterium avium complex
infections.
Action
Inhibits protein synthesis in bacteria at level of 30S ribosome.
Therapeutic Effects: Bactericidal action.
Spectrum: Most aminoglycosides notable for activity
against: P. aeruginosa, Klebsiella pneumoniae, E.coli,
Proteus, Serratia, Acinetobacter, Staphylococcus aureus.
In treatment of enterococcal infections, synergy
with a penicillin is required. Streptomycin and amikacin
also active against Mycobacterium.
Pharmacokinetics
Absorption: Well absorbed after IM administration.
IV administration results in complete bioavailability.
Some absorption follows administration by other
routes. Minimal systemic absorption with neomycin
(may accumulate in patients with renal failure).
Distribution: Widely distributed throughout extracellular
fluid; cross the placenta; small amounts enter
breast milk. Poor penetration into CSF (qwhen meninges
are inflamed).
Metabolism and Excretion: Excretion is 90%
renal.
Half-life: 2–4 hr (qin renal impairment).
TIME/ACTION PROFILE (blood levels*)
ROUTE ONSET PEAK DURATION
PO (neomycin)
rapid 1–4 hr N/A
IM rapid 30–90 min 6–24 hr
IV rapid 15–30 min† 6–24 hr
*All parenterally administered aminoglycosides.
†Postdistribution peak occurs 30 min after the end of a 30-
min infusion and 15 min after the end of a 1-hr infusion.
Contraindications/Precautions
Contraindicated in: Hypersensitivity to aminoglycosides;
Most parenteral products contain bisulfites
and should be avoided in patients with known intolerance;
Pedi: Products containing benzyl alcohol should
be avoided in neonates; Intestinal obstruction (neomycin
only).
Use Cautiously in: Renal impairment (dose adjustments
necessary; blood level monitoring useful in preventing
ototoxicity and nephrotoxicity); Hearing impairment;
Neuromuscular diseases such as myasthenia gravis; Obese patients (dose should be based on ideal
body weight); OB: Tobramycin and streptomycin may
cause congenital deafness; Lactation: Safety not established;
Pedi: Neonates haveqrisk of neuromuscular
blockade; difficulty in assessing auditory and vestibular
function and immature renal function; Geri: Difficulty in
assessing auditory and vestibular function and age-related
renal impairment.
Adverse Reactions/Side Effects
CNS: ataxia, vertigo. EENT: ototoxicity (vestibular
and cochlear). GU: nephrotoxicity. GI: Neomycin—
diarrhea, nausea, vomiting. F and E: hypomagnesemia.
MS: muscle paralysis (high parenteral doses).
Neuro:qneuromuscular blockade. Resp: apnea;
Tobramycin, Inhaln only, bronchospasm, wheezing.
Misc: hypersensitivity reactions.
Interactions
Drug-Drug: Inactivated by penicillins and cephalosporins
when coadministered to patients with renal
insufficiency. Possible respiratory paralysis after inhalation
anesthetics or neuromuscular blocking
agents.qincidence of ototoxicity with loop diuretics
or mannitol (IV).qincidence of nephrotoxicity with
other nephrotoxic drugs. Neomycin mayqanticoagulant
effects of warfarin. Neomycin maypabsorption
of digoxin and methotrexate.
Route/Dosage
Amikacin
IM, IV (Adults and Children): 5 mg/kg every 8 hr or
7.5 mg/kg every 12 hr (not to exceed 1.5 g/day). Mycobacterium
avium complex—7.5–15 mg/kg/day divided
every 12–24 hr.
IM, IV (Neonates): Loading dose—10 mg/kg; Maintenance
dose—7.5 mg/kg every 12 hr.
Renal Impairment
IM, IV (Adults): Loading dose—7.5 mg/kg, further
dosing based on blood level monitoring and renal function
assessment.
Gentamicin
Many regimens are used; most involve dosing adjusted
on the basis of blood level monitoring and assessment
of renal function.
IM, IV (Adults): 1–2 mg/kg every 8 hr (up to 6 mg/
kg/day in 3 divided doses); Once-daily dosing (unlabeled)—
4–7 mg/kg every 24 hr.
IM, IV (Children 5 yr): 2–2.5 mg/kg/dose every 8
hr; Once daily—5–7.5 mg/kg/dose every 24 hr; Cystic
fibrosis—2.5–3.3 mg/kg/dose every 6–8 hr; Hemodialysis—
1.25–1.75 mg/kg/dose postdialysis.
IM, IV (Children 1 mo–5 yr): 2.5 mg/kg/dose every
8 hr; Once daily—5–7.5 mg/kg/dose every 24 hr;
Cystic fibrosis—2.5–3.3 mg/kg/dose every 6–8 hr;
Hemodialysis—1.25–1.75 mg/kg/dose postdialysis.
IM, IV (Neonates full term and/or 1 wk): Weight
1200 g—2.5 mg/kg/dose every 18–24 hr; Weight
1200–2000 g—2.5 mg/kg/dose every 8–12 hr;
Weight2000 g—2.5 mg/kg/dose every 8 hr;
ECMO—2.5 mg/kg/dose every 18 hr, subsequent
doses based on serum concentrations; Once daily—
3.5–5 mg/kg/dose every 24 hr.
IM, IV (Neonates premature and/or 1 wk):
Weight1000 g—3.5 mg/kg/dose every 24 hr;
Weight 1000–1200 g—2.5 mg/kg/dose every 18–24
hr; Weight 1200 g—2.5 mg/kg/dose every 12 hr;
Once daily—3.5–4 mg/kg/dose every 24 hr.
IT (Adults): 4–8 mg/day.
IT (Infants 3 mo and Children): 1–2 mg/day.
IT (Neonates): 1 mg/day.
Topical (Adults and Children 1mo): Apply cream
or ointment 3–4 times daily.
Renal Impairment
IM, IV (Adults): Initial dose of 2 mg/kg. Subsequent
doses/intervals based on blood level monitoring and renal
function assessment.
Neomycin
PO (Adults): Preoperative intestinal antisepsis—1
g every hr for 4 doses, then 1 g every 4 hr for 5 doses or
1 g at 1 PM, 2 PM, and 11 PM on day before surgery;
Hepatic encephalopathy—1–3 g every 6 hr for 5–6
days; may be followed by 4 g/day chronically.
PO (Children): Preoperative intestinal antisepsis—
15 mg/kg every 4 hr for 2 days or 25 mg/kg at 1 PM, 2
PM, and 11 PM on day before surgery; Hepatic encephalopathy—
12.5–25 mg/kg every 6 hr for 5–6
days (maximum dose12 g/day).
Streptomycin
IM (Adults): Tuberculosis—1 g/day initially,pto 1 g
2–3 times weekly; Other infections—250 mg–1 g
every 6 hr or 500 mg–2 g every12 hr.
IM (Children): Tuberculosis—20 mg/kg/day (not to
exceed 1 g/day); Other infections—5–10 mg/kg
every 6 hr or 10–20 mg/kg every 12 hr.
Renal Impairment
IM (Adults): 1 g initially, further dosing determined by
blood level monitoring and assessment of renal function.
Tobramycin
IM, IV (Adults): 1–2 mg/kg every 8 hr or 4–6.6 mg/
kg/day every 24 hr.
IM, IV (Adults): 3–6 mg/kg/day in 3 divided doses,
or 4–6.6 mg/kg once daily.
IM, IV (Children 5 yr): 6–7.5 mg/kg/day divided
every 8 hr, up to 13 mg/kg/day divided every 6–8 hr in
cystic fibrosis patients (dosing interval may vary from every 6 hr–every 24 hr, depending on clinical situation).
IM, IV (Children 1 mo–5 yr): 7.5 mg/kg/day divided
every 8 hr, up to 13 mg/kg/day divided every 6–8
hr in cystic fibrosis.
IM, IV (Neonates): Preterm 1000 g—3.5 mg/kg/
dose every 24 hr; 0–4 weeks, 1200 g—2.5 mg/kg/
dose every 18 hr; Postnatal age 7 days—2.5 mg/
kg/dose every 12 hr; Postnatal age 8 days, 1200–
2000 g—2.5 mg/kg/dose every 8–12 hr; Postnatal
age 8 days, 2000 g—2.5 mg/kg/dose every 8 hr.
Inhaln (Adults and Children 6 yr): Nebulizer solution—
300 mg twice daily for 28 days, then off for 28
days, then repeat cycle; Powder for inhalation—Inhale
contents of four 28-mg capsules twice daily for 28
days, then off for 28 days, then repeat cycle.
Renal Impairment
IM, IV (Adults): 1 mg/kg initially, further dosing determined
by blood level monitoring and assessment of
renal function.
Availability
Amikacin (generic available)
Injection: 250 mg/mL.
Gentamicin (generic available)
Injection: 10 mg/mL, 40 mg/mL. Premixed injection:
60 mg/50 mL, 80 mg/50 mL, 80 mg/100 mL, 100
mg/50 mL, 100 mg/100 mL, 120 mg/100 mL. Topical
cream: 0.1%. Topical ointment: 0.1%.
Neomycin (generic available)
Tablets: 500 mg. In combination with: other topical
antibiotics or anti-inflammatory agents for skin, ear,
and eye infections. See Appendix B.
Streptomycin (generic available)
Lyophilized powder for injection: 1 g/vial.
Tobramycin (generic available)
Injection: 10 mg/mL, 40 mg/mL. Nebulizer solution
(TOBI, Kitabis Pak): 300 mg/5 mL. Nebulizer solution
(Bethkis): 300 mg/4 mL. Powder for inhalation
(TOBI Podhaler): 28 mg/capsule. Powder for
injection: 1200 mg/vial. Premixed injection: 80 mg/
100 mL.
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