a) It is frequently found in combination with other antibacterials (i.e., polymixin, gramicidin, dacitracin, etc) and corticosteroids for topical use.

1) Retinopathy and visual loss with intraocular administration. Apnea and neuromuscular blockade may occur when aminoglycosides are given rapidly IV with neuromuscular blocking agents, due to aminoglycosides' inhibition of acetylcholine release from presynaptic nerve terminals; patients with abnormal neuromuscular junction function (eg, myasthenia gravis, botulism) can develop respiratory failure or weakness after use of aminoglycosides alone. Rash and hypersensitivity reactions can occur.

1) Toxicity is more closely associated with trough levels of the drug than peak levels. Renal damage (acute tubular necrosis; usually reversible), ototoxicity (irreversible), and vestibular toxicity (irreversible) are most common. Renal injury may often go unnoticed until significant injury has occurred, given the delay between when renal injury occurs and when the elevation in creatinine is evident.

1) Treatment is symptomatic and supportive. Maintain good urine output (3 to 6 mL/kg/hr) with IV fluids. For mild allergic reactions, treat with antihistamines; if severe, airway management, epinephrine, ECG monitoring, IV fluids.

1) GI decontamination is not indicated as aminoglycosides are poorly absorbed orally. OCULAR: Copious irrigation with normal saline.

1) Endotracheal intubation and mechanical ventilation may be required in patients with severe allergic reactions, but this is rare.

1) None

1) Hemodialysis should be considered in renal failure only. Ticarcillin forms a renally eliminated complex with gentamicin and enhances elimination, but should only be used early after large overdoses with apparent toxicity or in renal failure when there is a significant risk of toxicity.

1) HOME CRITERIA: The vast majority of exposures will occur in a healthcare setting. Inadvertent ingestion of ophthalmic, otic or topical preparations can be observed at home.
2) OBSERVATION CRITERIA: Patients with significant overdose should have renal function monitoring and auditory testing performed.
3) ADMISSION CRITERIA: Patients with worsening renal function may require in-patient monitoring and dialysis.
4) CONSULT CRITERIA: Consult a toxicologist after large overdose or if effects are not consistent with the exposure.

1) Poorly absorbed orally (less than 10%). Peak serum concentrations of aminoglycosides are typically reached 30 to 60 minutes after intravenous injection or 30 to 90 minutes after intramuscular injection. Volumes of distribution range from 0.2 to 0.4 L/kg; renally eliminated. Terminal half-life ranges from 1.5 to 4 hours in healthy adults with normal renal function.

1) Other causes of renal failure including medications, infection, shock, or obstruction.

1) At the commercially available concentration, only neomycin showed a toxic effect, as measured by the corneal epithelial cells' ability to take up labeled thymidine after 5 minutes of exposure (Lass et al, 1989).

1) CASE REPORT: Judson (1989) reports a case of a cataract surgery patient who received a standard subconjunctival injection of 20 mg tobramycin. On the fundus exam, a whitish macular infarction and intraretinal hemorrhage were noted, and irreversible loss of acuity occurred.

1) Conjunctival defects healed within 13 days of discontinuing aminoglycoside treatment in all patients (Davison et al, 1991).

1) With neomycin, ototoxicity is characterized by a latency of 2 to 6 weeks after onset of therapy, hearing loss often being noticed days to weeks after the drug has been discontinued.
2) Ototoxicity (eg, deafness and vertigo) has been reported following use of topical neomycin and otic solutions containing gentamicin (Morrell et al, 1985; Lind & Kristiansen, 1986; Leliever, 1985).
3) Gentamicin and tobramycin are toxic to both cochlea and vestibule. Amikacin is more cochleotoxic; kanamycin and streptomycin are more vestibulotoxic (Aran, 1995) (Barkley & Begg, 1994).
4) Matz (1986) reported unilateral, delayed-onset, and reversible auditory and vestibular toxicity as a result of therapy with gentamicin, tobramycin, amikacin, and netilmicin (Matz, 1986).
5) SUSCEPTIBILITY: Patient susceptibility to ototoxicity associated with aminoglycoside administration may be dependent on several factors, including route of administration, genotype, and preexisting medical conditions (ie, renal insufficiency) (Guthrie, 2008).
6) CASE REPORT: Acute and residual ototoxicity was reported in a 39-year-old patient receiving 6 grams of neomycin IM (Krumlovsky et al, 1972).
7) CASE REPORT: CHRONIC topical application of 1% neomycin to large wounds precipitated severe hearing loss in an adult within 3 weeks of beginning the applications. A total of approximately 7 liters of the neomycin solution was applied to the wounds (Johnson, 1988).
8) VESTIBULOTOXICITY: Halmagyi et al (1994) described 36 patients with gentamicin vestibulotoxicity. Effects included ataxia (worse in the dark and on uneven surfaces), vertical oscillopsia while walking, hearing loss, positive Romberg on soft surfaces, decreased visual acuity on rapid head shaking, and saccades on rapid passive head rotation. All patients had bilateral impairment of lateral semicircular canal function on testing. Two patients had sensorineural hearing loss and 16 had increases in serum creatinine of 0.3 mg/dL or more. Vestibulotoxicity was not related to peak or trough serum concentrations or gentamicin dose (Halmagyi et al, 1994).
9) INCIDENCE: El Bakri et al (1998) report an incidence of ototoxicity of 18% (5 of 28 patients) in patients receiving once a day gentamicin for febrile neutropenia (El Bakri et al, 1998).

1) GENTAMICIN/CASE REPORT: A 65-year-old man with end-stage renal disease and on continuous ambulatory peritoneal dialysis developed irreversible vestibular dysfunction and hearing loss after inadvertently receiving gentamicin (1.2 mg/kg intravenously and 200 mg/kg intraperitoneally within 2 days) for treatment of peritonitis. A neurologic exam revealed that the patient had truncal ataxia and laboratory data indicated a serum gentamicin level of 220 mcg/mL. Following hemodialysis and hemoperfusion over a 2-day period, along with continuous peritoneal dialysis, the patient's serum gentamicin level decreased to 10.5 mcg/mL. Although there was improvement with vestibular function, the patient continued to experience moderate hearing loss 3 weeks later (Lu et al, 1996).
2) GENTAMICIN/CASE REPORT: One neonate who received 85 mg of gentamicin for 2 doses developed acute nephrotoxicity which resolved within 3 days and a questionable response to audiometric testing at 18 months of age (2,000 to 4,000 Hz) with normal brainstem evoked potentials (Fuquay et al, 1981).

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) NEPHROTOXICITY

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) ANIMAL STUDIES - Treatment of pregnant rat and guinea pig dams with aminoglycosides resulted in functional and morphologic renal damage in one and three-day-old neonates (Kacew & Bergeron, 1990).

1) Small amounts of aminoglycosides may be excreted into breast milk, therefore it is recommended that the aminoglycosides be administered with caution during lactation due to the risk of adverse effects to the infant (Briggs et al, 1998).

A) Patients with worsening renal function may require in-patient monitoring and dialysis.

A) The vast majority of exposures will occur in a healthcare setting. Inadvertent ingestion of ophthalmic, otic or topical preparations can be observed at home.

A) Consult a toxicologist after large overdose or if effects are not consistent with the exposure.

A) Patients with significant overdose should have renal function monitoring and auditory testing performed.

1) Monitor renal function and serum electrolytes following overdose.
2) Serum concentrations are used for therapeutic drug monitoring for many aminoglycosides and can be used to confirm the diagnosis.
3) Monitor for hearing loss (audiometry).

1) SUMMARY
2) BRONCHOSPASM
3) CORTICOSTEROIDS
4) MILD CASES
5) MODERATE CASES
6) SEVERE CASES
7) AIRWAY MANAGEMENT
8) MONITORING
9) HYPOTENSION
10) H1 and H2 ANTIHISTAMINES
11) DYSRHYTHMIAS
12) OTHER THERAPIES

1) Maintain good urine output (3 to 6 mL/kg/hr) with intravenous fluids. This appears to be the treatment of choice for a single acute overdose of aminoglycosides (Bolam et al, 1982).

1) CASE REPORT: A 70-year-old man, undergoing a vitrectomy for retinal detachment, inadvertently received an intravitreal injection of 0.5 to 1 mL of gentamicin (40,000 mcg/mL). Immediate vitreous lavage with 500 mL of a balanced salt solution was applied with continuous aspiration of the macular zone. Following the procedure, 1 mL of air was injected into the eye and the patient was in a prone position for 3 days. There were no signs of toxicity and, on post-operative day 1, the patient's vision was 6/12, the same as at admission pre-operatively. A fundus examination showed that the retina was attached and there was no sign of vascular damage. Five months later, a follow-up exam showed improvement of his visual acuity at 6/9 with no evidence of perfusion abnormality (Burgansky et al, 2002).

a) AMIKACIN: Five accidental overdoses of amikacin (2 g/dose; 3 g/1 to 6 doses; and 18 g/dose) have been reported (Ho et al, 1979; Flandrois et al, 1979; Green et al, 1981). Observations from these cases indicate that no therapy is necessary after a high overdose of amikacin if the patient has normal renal function and the overdose was not immediately discovered.
b) AMIKACIN: A woman inadvertently received 18 grams of amikacin over 4 hours. Serum levels were increased at least 10-fold over the recommended level. The drug was excreted promptly in the urine following saline diuresis (0.15 M NaCl infusion).
c) GENTAMICIN: Vertigo was reported in a 50-year-old patient 1 week following a 6-week course of an otic solution containing gentamicin (Leliever, 1985).
d) GENTAMICIN: A 30-year-old woman inadvertently received 158 mg gentamicin via epidural catheter over 5 hours; back pain was the only observed effect (Sigg & Leikin, 1999).
e) NEOMYCIN: Topical neomycin was also implicated as the cause of deafness in children and adults when applied to burns and wounds and when instilled into body cavities (Bamford & Jones, 1978).
f) NEOMYCIN: Acute administration of 6 grams of neomycin IV in a 39-year-old patient resulted in acute nephrotoxicity and ototoxicity, with residual deafness (Krumlovsky et al, 1972).

a) KANAMYCIN: Montalbo & Smith (1969) described overdose of kanamycin secondary to erroneous drug administration in a 10-month-old infant. The dose of 1 gram IM (10 times the calculated daily dose) was administered. No distress was observed 1 hour following drug administration; however, peritoneal dialysis was instituted (Montalbo & Smith, 1969).
b) KANAMYCIN: Accidental administration of 66 mg and 200 mg, respectively, in 2 preterm infants resulted in no ototoxicity or nephrotoxicity. Exchange transfusions were performed in both patients. The exchange was reported not to enhance the elimination of the drug, although no data were presented (Bolam et al, 1982).
c) GENTAMICIN: Only 6 published cases describe the inadvertent administration of large doses of gentamicin to neonates (50 mg IM for 2 doses; 85 mg IV for 2 doses; 125 mg IM single dose; and 152 mg IV single dose) (Fuquay et al, 1981; Bolam et al, 1982; Smith, 1982; Koren et al, 1986). In all but 1 case, no evidence of ototoxicity was present at follow-up more than 1 year later.
d) GENTAMICIN: Accidental injection of 320 mg of gentamicin in a 16-month-old infant with normal renal function did not result in renal or otologic sequelae (Rigal et al, 1981).
e) NEOMYCIN: Morrell (1985) reported deafness in a preterm infant diagnosed 11 months after use of an antibiotic spray containing neomycin for the treatment of a cord infection. Concomitant intravenous gentamicin therapy was also administered for a period of 3 days (Morrell et al, 1985).
f) NEOMYCIN: Topical neomycin was also implicated as the cause of deafness in children and adults when applied to burns and wounds and when instilled into body cavities (Bamford & Jones, 1978).

1) AMIKACIN: 15 mg/kg/day IM or IV divided every 8 to 12 hours (Prod Info amikacin sulfate IM, IV injection, 2009).
2) GENTAMICIN : Depending on the severity of the infection, the recommended dose is 3 to 5 mg/kg/day IV in 3 or 4 equally divided doses (Prod Info gentamicin sulfate, sodium chloride injection, 2004).
3) NEOMYCIN: For treatment of hepatic encephalopathy, 4 to 12 g orally daily, given in divided doses, for 5 to 6 days (Prod Info neomycin sulfate oral tablets, 2009).
4) TOBRAMYCIN INHALATION POWDER: For treatment of cystic fibrosis, 4 capsules (28 mg/capsule) by inhalation twice daily (every 12 hours but not less than 6 hours apart) for 28 days. Therapy should be given as a 28 days on/28 days off cycle (Prod Info TOBI(R) PODHALER(TM) oral inhalation, 2013).
5) TOBRAMYCIN INHALATION SOLUTION: For treatment of cystic fibrosis, 300 mg (1 ampule) by inhalation twice daily (every 12 hours but not less than 6 hours apart) for 28 days. Therapy should be given as a 28 days on/28 days off cycle (Prod Info KITABIS(TM) PAK inhalation solution, 2014; Prod Info BETHKIS(R) oral inhalation solution, 2012; Prod Info TOBI(R) inhalation solution, 2009)
6) TOBRAMYCIN SULFATE: Depending on the severity of the infection, the recommended dose is 3 to 5 mg/kg/day IV/IM in 3 or 4 equally divided doses (Prod Info tobramycin IM, IV injection, 2008).

1) AMIKACIN
2) GENTAMICIN
3) TOBRAMYCIN

a) OINTMENTS
b) ADULTS
c) PEDIATRIC

a) ADULTS: Inadvertent administration to adults of 2, 3, 6, and 18 gram single doses has not resulted in nephrotoxicity or ototoxicity (Green et al, 1981; Flandrois et al, 1979; Ho et al, 1979).

a) INFANT: Inadvertent administration of 66 milligrams and 200 milligrams, respectively, to two neonates did not result in ototoxicity or nephrotoxicity (Bolam et al, 1982).
b) INFANT: Administration of 1 gram intramuscularly to a 10-month-old infant resulted in no evidence of renal or otic effects (Montalbo & Smith, 1969).

a) NEONATES: Inadvertent administration of 25 milligrams, 50 milligrams, 85 milligrams, 125 milligrams, and 152 milligrams intramuscularly or intravenously resulted in acute nephrotoxicity in 4 cases, but no residual effects (Fuquay et al, 1981; Bolam et al, 1982; Smith, 1982; Koren et al, 1986).
b) INFANT: Inadvertent administration of 320 milligrams resulted in no adverse sequelae in a 16-month-old infant (Rigal et al, 1981).
c) CASE REPORT: A 14-month-old girl received a 500 mg (56 mg/kg) dose of gentamicin. Serum gentamicin concentration was 89 mg/L 2 hours later. A 4 hour hemodialysis session was initiated 4 hours after the dose. She did not develop nephrotoxicity or ototoxicity. Her serum gentamicin concentration was 3.4 mg/L after 4 hours of hemodialysis and 2.3 mg/L 4 hours after the completion of hemodialysis (Schurman et al, 2009).
d) CASE REPORT/ADULT: A 70-year-old man, undergoing a vitrectomy for retinal detachment, inadvertently received an intravitreal injection of 0.5 to 1 milliliter of gentamicin (40,000 micrograms/milliliter). Immediate vitreous lavage with 500 milliliters of a balanced salt solution was applied with continuous aspiration of the macular zone. Following the procedure, 1 milliliter of air was injected into the eye and the patient was in a prone position for 3 days. There were no signs of toxicity and, on post-operative day 1, the patient's vision was 6/12, the same as at admission pre-operatively. A fundus examination showed that the retina was attached and there was no sign of vascular damage. Five months later, a follow-up exam showed improvement of his visual acuity at 6/9 with no evidence of perfusion abnormality (Burgansky et al, 2002).

1) SPECIFIC SUBSTANCE

1) The most common and serious toxic effect of aminoglycoside use in animals is renal damage. A report exists of 5 dogs on one farm who exclusively ate pig feed containing hygromycin B. All dogs developed irreversible ototoxicity and deafness (Watson & Burnett, 1989).

1) Begin treatment immediately.
2) Keep animal warm and do not handle unnecessarily.
3) Sample vomitus, blood, urine, and feces for analysis.

1) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
2) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
3) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

1) DOGS/CATS
2) RUMINANTS/HORSES/SWINE

1) MAINTAIN VITAL FUNCTIONS - as necessary.
2) VENTILATORY SUPPORT including oxygen, intubation, and artificial ventilation may be necessary in patients experiencing neuromuscular blockade.
3) FLUIDS - Begin intravenous administration of 0.9 percent NaCl or other solution at a rate of up to 60 milliliters/kilogram/hour.
4) CALCIUM chloride or gluconate may assuage signs of neuromuscular blockade. Intravenous infusion of calcium should be performed with EKG monitoring for arrythmias (Beasley et al, 1989).
5) SUPPORTIVE CARE - Other supportive care may be necessary for several days.
6) DIURETICS - DO NOT USE loop diuretics.

1) MAINTAIN VITAL FUNCTIONS - Secure airway, supply oxygen and begin supportive fluid therapy if necessary.
2) VENTILATORY SUPPORT including oxygen, intubation, and artificial ventilation may be necessary in patients experiencing neuromuscular blockade.
3) FLUIDS -
4) SUPPORTIVE CARE for several days may be necessary.
5) DIURETICS - DO NOT USE loop diuretics.

1) AMIKACIN -
2) GENTAMICIN -

1) No specific information on a minimal toxic dose was available at the time of this review.

A) GENERAL TREATMENT
B) ANIMAL POISON CONTROL CENTERS

A) GASTRIC DECONTAMINATION

a) Available in 1 gram vials for injection, 50 mg/ml; trade names: Amiglyde-V(R) and Amikin(R) (Plumb, 1989)

a) Injectable: 40 mg/ml in 20 ml vial; trade names include Gentocin(R).
b) Otic: 3 mg/ml gentamicin in bottles of 7.5 and 15 ml; trade names include Gentocin(R) Otic and Garramycin(R).
c) Ophthalmic: 3 mg/g gentocin in 3.5 g tube of ointment; trade names include Genoptic(R) (Plumb, 1989).

a) Commercial swine feeds contain hygromycin B as a maintenance anthelmintic (Plumb, 1989).

a) Five unrelated dogs on an Australian farm became deaf within 8 months. Although one dog had a history of exposure to topical aminoglycosides to treat chronic otitis externa, the other four were unexposed.

a) Administer aminoglycoside antibiotics cautiously and only when absolutely necessary while neuromuscular blocking agents are used; aminoglycosides prolong their effect (Beasley et al, 1989).
b) Renal dysfunction may occur in 10 to 20 percent of all courses of therapy with aminoglycosides (Beasley et al, 1989).