aminoglycoside

aminoglycoside /ami·no·gly·co·side/ (-gli´ko-sīd) any of a group of antibacterial antibiotics (e.g., streptomycin, gentamicin) derived from various species of Streptomyces or produced synthetically; they interfere with the function of bacterial ribosomes.

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a·mi·no·gly·co·side (-mn-glk-sd, m-n-)

n.

Any of a group of bacteriocidal antibiotics derived from species of Streptomyces or Micromonosporum that are effective against aerobic gram-negative bacilli and Mycobacterium tuberculosis.

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aminoglycoside

any of a group of bacterial antibiotics derived from various species of Streptomyces that interfere with the function of bacterial ribosomes. These compounds contain an inositol moiety substituted with two amino or guanidino groups and with one or more sugars or aminosugars.

The aminoglycosides include gentamicin, streptomycin, tobramycin, amikacin, kanamycin and neomycin. They are used to treat infections caused by gram-negative organisms and are classified as bactericidal agents because of their interference with bacterial replication. All of the aminoglycoside antibiotics are highly toxic, requiring monitoring of blood serum levels at frequent intervals and careful observation of the patient for early signs of toxicity, particularly ototoxicity and nephrotoxicity.

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aminoglycoside 

Any one of a group of antibiotics composed of amino sugars in glycoside linkage which act by interfering with the synthesis of bacterial proteins. It is used in the treatment of infections caused by Gram-negative bacteria. Examples: framycetin, gentamicin, neomycin and tobramycin.

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streptomycin sulfate

Pharmacologic class: Aminoglycoside

Therapeutic class: Anti-infective

Pregnancy risk category D

FDA Boxed Warning

• Risk of severe neurotoxic reactions (including vestibular and cochlear dysfunction) is markedly higher in patients with impaired renal function or prerenal azotemia. Incidence of clinically detectable, irreversible vestibular damage is particularly high.
• Neurotoxicity can lead to respiratory paralysis from neuromuscular blockade, especially when drug is given soon after anesthesia or muscle relaxants.
• Monitor renal function carefully; reduce dosage in patients with renal impairment or nitrogen retention.
• Avoid concurrent or sequential use of other neurotoxic or nephrotoxic drugs, including cephaloridine, colistin, cyclosporine, gentamicin, kanamycin, neomycin, paromomycin, polymyxin B, tobramycin, and viomycin.
• Reserve parenteral administration for settings where adequate laboratory and audiometric studies are available during therapy.

Action

Binds to 30S ribosomal subunit, inhibiting protein synthesis in bacterial cell, which causes misreading of genetic code and, ultimately, cell death

Availability

Injection: 400 mg/ml in 2.5-ml ampules, 200 mg/ml in 1-g vials

⊘Indications and dosages

➣ Adjunct in tuberculosis and other mycobacterial infections

Adults: 15 mg/kg/day I.M., up to 1 g/day

Children: 20 to 40 mg/kg I.M. daily, up to 1 g/day

➣ Enteroccocal or streptococcal infections

Adults: 1 g I.M. b.i.d. for 1 week, then 500 mg I.M. b.i.d. for 1 week. For enterococcal endocarditis, 1 g I.M. b.i.d. given with penicillin for 1 week, then 500 mg I.M. b.i.d. for 4 weeks.

➣ Brucellosis

Adults: 1 g I.M. once or twice daily with tetracycline or doxycycline for 1 week, then once daily for at least 1 more week

➣ Tularemia

Adults: 1 to 2 g I.M. daily in divided doses for 7 to 14 days until patient is afebrile for 5 to 7 days. For tularemia caused by Francisella tularensis, 1 g I.M. b.i.d. for 10 days or 7.5 to 10 mg/kg I.M. b.i.d. for 10 to 14 days.

➣ Plague caused by Yersinis pestis

Adults: 1 g I.M. b.i.d. for 10 to 14 days

Dosage adjustment

• Renal impairment
• Elderly patients

Off-label uses

• Mycobacterium avium-intracellulare complex in AIDS patients

Contraindications

• Hypersensitivity to drug, other aminoglycosides, or bisulfites

Precautions

Use cautiously in:
• renal impairment, hearing impairment, neuromuscular disease (such as myasthenia gravis)
• elderly patients
• pregnant or breastfeeding patients
• infants and neonates (safety not established).

Administration

• Inject I.M. deep into upper outer quadrant of buttock.
• Alternate injection sites.
• Know that drug may be given with other antituberculars.
• Be aware that streptomycin will be withdrawn after several months or when bacteriologic smears are negative and other antituberculars are continued for 1 year.

Route	Onset	Peak	Duration
I.M.	Rapid	30-90 min	Unknown

Adverse reactions

CNS: vertigo, numbness and tingling, peripheral neuropathy, myasthenia gravis-like syndrome, neuromuscular blockade, seizures

CV: myocarditis

EENT: amblyopia, ototoxicity

GI: nausea, vomiting

GU: azotemia, nephrotoxicity

Hematologic: eosinophilia, hemolytic anemia, pancytopenia, leukopenia, thrombocytopenia

Hepatic: hepatic necrosis

Musculoskeletal: muscle weakness, twitching

Respiratory: apnea

Skin: rash, urticaria, exfoliative dermatitis, toxic epidermal necrolysis, angioedema

Other: fever, superinfection, serum sickness, anaphylaxis

Interactions

Drug-drug. Acyclovir, amphotericin B, cephalosporin, cisplatin, potent diuretics, vancomycin: increased risk of ototoxicity and nephrotoxicity

Depolarizing and nondepolarizing neuromuscular blockers, general anesthetics: potentiation of neuromuscular blockade

Dimenhydrinate: masking of ototoxicity symptoms

Indomethacin: increased streptomycin peak and trough blood levels

Parenteral penicillins (ampicillin, ticarcillin): streptomycin inactivation

Drug-diagnostic tests. Bilirubin, blood urea nitrogen, creatinine, lactate dehydrogenase, nonprotein nitrogen: increased levels

Granulocytes, hemoglobin, platelets, white blood cells: decreased levels

Patient monitoring

• Draw blood for peak drug level 1 hour after I.M. injection. Draw blood for trough level just before next dose.
• Monitor liver and kidney function tests. Watch for evidence of hepatotoxicity and nephrotoxicity.
• Monitor temperature. Stay alert for fever and other signs and symptoms of superinfection.
• Assess neurologic status and sensory function carefully. Watch closely for neurotoxicity, neuromuscular blockade, and seizures.
• Assess for signs and symptoms of ototoxicity.
• Monitor CBC. Watch for evidence of blood dyscrasias.

Patient teaching

• Instruct patient to report unusual bleeding or bruising.
☞ Inform patient that drug can be toxic to many body systems. Teach him to recognize and immediately report serious adverse reactions.
☞ Tell patient drug may promote growth of certain organisms. Advise him to immediately report signs and symptoms of superinfection.
• Inform patient that drug may impair cognitive, motor, and sensory function. Advise him to use caution when driving and performing other hazardous activities.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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tobramycin sulfate

Pharmacologic class: Aminoglycoside

Therapeutic class: Anti-infective

Pregnancy risk category B (inhalation, ophthalmic), D (parenteral)

FDA Boxed Warning

The following boxed warnings apply to parenteral administration only:
• When giving drug by injection, observe patient closely for potential ototoxicity and nephrotoxicity. Rarely, nephrotoxicity doesn't emerge until first few days after therapy ends.
• Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. Auditory changes are irreversible and usually bilateral. Eighth-nerve impairment and nephrotoxicity also may develop, mainly in patients with preexisting renal damage and in those with normal renal function who receive drug for longer periods or in higher doses than those recommended. Other neurotoxicity manifestations may include numbness, skin tingling, muscle twitching, and seizures. Risk of drug-induced hearing loss increases with degree of exposure to high peak or high trough drug blood levels. Patients who develop cochlear damage may lack symptoms during therapy to warn of eighth-nerve toxicity, and partial or total irreversible bilateral deafness may continue to develop after withdrawal.
• Monitor renal and eighth-nerve function closely in patients with known or suspected renal impairment and in those whose renal functional initially is normal but who develop signs of renal dysfunction during therapy. Monitor peak and trough drug blood levels periodically during therapy; avoid levels above 12 mcg. Rising trough levels (above 2 mcg) may indicate tissue accumulation. Such accumulation, excessive peak levels, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity. Examine urine for decreased specific gravity and increased protein, cells, and casts. Measure blood urea nitrogen (BUN), serum creatinine, and creatinine clearance periodically. When feasible, obtain serial audiograms. Evidence of impairment of renal, vestibular, or auditory function warrants drug withdrawal or dosage adjustment.
• Avoid concurrent or sequential use of other neurotoxic or nephrotoxic antibiotics, especially other aminoglycosides (such as amikacin, gentamicin, kanamycin, neomycin, and streptomycin), cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin. Advanced age and dehydration also increase risk.
• Don't give concurrently with potent diuretics (such as furosemide and ethacrynic acid), because these drugs are also ototoxic. Also, I.V. diuretics may increase tobramycin toxicity by altering antibiotic serum and tissue levels.
• Use drug cautiously in premature infants and neonates.
• Drug may harm fetus when given to pregnant women.

Action

Interferes with protein synthesis in bacterial cell by binding to 30S ribosomal subunit

Availability

Injection: 10 mg/ml, 40 mg/ml, 1.2-g vial

Nebulizer solution: 300 mg/5 ml in 5-ml ampule

Ophthalmic ointment: 0.3%

Ophthalmic solution: 0.3%

Pediatric solution for injection: 20 mg/2 ml

⊘Indications and dosages

➣ Serious infections caused by susceptible organisms

Adults: 3 mg/kg/day I.V. or I.M. in evenly divided doses q 8 hours. For life-threatening infections, may increase up to 5 mg/kg/day I.V. or I.M. in three or four evenly divided doses, then reduce to 3 mg/kg/day as soon as possible.

Children older than 1 week: 6 to 7.5 mg/kg/day in three or four evenly divided doses, such as 2 to 2.5 mg/kg I.V. or I.M. q 8 hours or 1.5 to 1.9 mg/kg I.V. or I.M. q 6 hours

Neonates less than 1 week old: Up to 4 mg/kg/day I.V. or I.M. in evenly divided doses q 12 hours

➣Pseudomonas aeruginosa in cystic fibrosis patients

Adults and children older than age 6: 300 mg inhalation b.i.d. (preferably q 12 hours but no less than 6 hours apart) for 28 days, then off for 28 days; then repeat cycle

➣ Ocular infections caused by susceptible organisms

Adults and children: For mild to moderate infections, apply a ribbon of ophthalmic ointment (approximately 1 cm) to infected eye two or three times daily, or instill one to two drops of ophthalmic solution into infected eye q 4 hours. For severe infections, apply ophthalmic ointment q 3 to 4 hours or instill two drops of ophthalmic solution into infected eye q 30 to 60 minutes; decrease dosing frequency when improvement occurs. Therapy should continue for at least 48 hours after infection is under control.

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug, other aminoglycosides, bisulfites (with some products), or benzyl alcohol (in neonates, with some products)

Precautions

Use cautiously in:
• renal or hearing impairment, neuromuscular diseases, obesity
• elderly patients
• pregnant or breastfeeding patients
• neonates and premature infants.

Administration

• Dilute I.V. dose in 50 to 100 ml of normal saline solution or dextrose 5% in water. For child, smaller volumes are needed.
• Infuse over at least 30 minutes. Flush line after administration.
• Give cephalosporins or penicillin, if ordered, 1 hour before or after tobramycin.
• Give inhalation doses by nebulizer over 10 to 15 minutes.

Route	Onset	Peak	Duration
I.V.	Rapid	15-30 min	Unknown
I.M.	Rapid	30-90 min	Unknown
Inhalation, ophthalmic	Unknown	Unknown	Unknown

Adverse reactions

CNS: confusion, lethargy, headache, delirium, dizziness, vertigo

EENT: eye stinging (with ophthalmic form), ototoxicity, hearing loss, roaring in ears, tinnitus

GI: nausea, vomiting, diarrhea, stomatitis

GU: proteinuria, oliguria, nephrotoxicity

Hematologic: anemia, eosinophilia, leukocytosis, leukopenia, thrombocytopenia, granulocytopenia

Metabolic: hypocalcemia, hyponatremia, hypokalemia, hypomagnesemia

Musculoskeletal: muscle weakness

Respiratory: apnea

Skin: rash, urticaria, itching

Other: superinfection, fever, pain and irritation at injection site

Interactions

Drug-drug. Cephalosporins, vancomycin: increased risk of nephrotoxicity

Dimenhydrinate: masking of ototoxicity symptoms

General anesthetics, neuromuscular blockers: increased neuromuscular blockade and respiratory depression

Indomethacin: increased tobramycin trough and peak levels

Loop diuretics: increased risk of ototoxicity

Penicillins: physical incompatibility, tobramycin inactivation when mixed in same I.V. solution

Polypeptide anti-infectives: increased risk of respiratory paralysis and renal dysfunction

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin, BUN, creatinine, lactate dehydrogenase, nonprotein nitrogen, urine protein: increased levels

Calcium, granulocytes, hemoglobin, magnesium, platelets, potassium, sodium, white blood cells: decreased levels

Patient monitoring

• Draw sample for peak drug level 1 hour after I.M. or 30 minutes after I.V. administration. Draw sample for trough level just before next dose.
• Assess liver and kidney function tests.
• Monitor CBC with white cell differential.
• Closely monitor patient's hearing.

Patient teaching

• Advise patient to report new signs or symptoms of infection.
• With inhalation form, teach patient how to use nebulizer. Instruct him to administer dose over 10 to 15 minutes by breathing normally through mouthpiece while sitting or standing. Remind him to use only the hand-held nebulizer and compressor originally dispensed with drug. Advise him to use a nose clip to help him breathe through his mouth. If he uses other inhaled drugs, instruct him to take tobramycin last.
• Teach patient proper use of eye drops. Caution him not to touch dropper to eye or any other surface.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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aminoglycoside

Therapeutics Any of a family of broad-spectrum antibiotics–amikacin, gentamicin, kanamycin, netilmicin, neomycin, framycetin, streptomycin, tobramycin, which are used primarily against aerobic gram-negative bacteria Pharmacodynamics Poorly absorbed per os, poor penetration of CNS–BBB, rapid excretion if kidneys are normal Types Gentamicin, streptomycin, tobramycin Toxicity Dose-related–kidneys, vestibular, auditory, and neuromuscular systems, minor skin rash, drug fever, ↓ Mg2+, ↓ Ca2+, ↓ K+; it is common practice to monitor Pts receiving AGs. See Therapeutic drug monitoring.