Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Reviewed/Revised May 2022
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* Should be used topically or orally only.


Aminoglycosides are poorly absorbed orally but are well absorbed from the peritoneum, pleural cavity, joints , and from denuded skin.

Aminoglycosides are usually given IV but may be given IM if IV access is unavailable. Aminoglycosides are distributed well into extracellular fluid except for vitreous humor, cerebrospinal fluid, respiratory secretions, and bile (particularly in patients with biliary obstruction). Intravitreous injection is required to treat endophthalmitis. Intraventricular injection is often required to reach intraventricular cerebrospinal fluid levels high enough to treat meningitis.

Aminoglycosides are excreted by glomerular filtration and have a serum half-life of 2 to 3 hours; the half-life increases exponentially as the glomerular filtration rate falls (eg, in renal insufficiency, in older people).

Indications for Aminoglycosides

Aminoglycosides are used for

Aminoglycosides are active against most gram-negative aerobic and facultative anaerobic bacilli but lack activity against anaerobes and most gram-positive bacteria, except for most staphylococci Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more Staphylococcal Infections ; however, some gram-negative bacilli and staphylococci are resistant.

Aminoglycosides that are active against P. aeruginosa include tobramycin (particularly), gentamicin, and amikacin. Streptomycin, neomycin, and kanamycin are not active against P. aeruginosa. Gentamicin and tobramycin have similar antimicrobial spectra against gram-negative bacilli, but tobramycin is more active against P. aeruginosa, and gentamicin is more active against Serratia marcescens. Amikacin is frequently active against gentamicin- and tobramycin-resistant pathogens.

Aminoglycosides are infrequently used alone, except when used for plague Plague and Other Yersinia Infections Plague is caused by the gram-negative bacterium Yersinia pestis. Symptoms are either severe pneumonia or large, tender lymphadenopathy with high fever, often progressing to septicemia... read more Plague and Other <i >Yersinia</i> Infections and tularemia Tularemia Tularemia is a febrile disease caused by the gram-negative bacterium Francisella tularensis; it may resemble typhoid fever. Symptoms are a primary local ulcerative lesion, regional lymphadenopathy... read more Tularemia . They are usually used with a broad-spectrum beta-lactam for severe infection suspected to be due to a gram-negative bacillary species. However, because of increasing aminoglycoside resistance, a fluoroquinolone can be substituted for the aminoglycoside in initial empiric regimens depending on the susceptibility patterns to fluoroquinolones in the local community. If the pathogen is found to be susceptible to the accompanying antibiotic, the aminoglycoside can be stopped after 2 to 3 days unless an aminoglycoside-susceptible P. aeruginosa is identified.

Gentamicin or, less commonly, streptomycin may be used with other antibiotics to treat endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more Infective Endocarditis due to streptococci or enterococci. Enterococcal resistance to aminoglycosides has become a common problem. Because treatment of enterococcal endocarditis requires prolonged use of a potentially nephrotoxic and ototoxic aminoglycoside plus a bacterial cell wall–active drug (eg, penicillin, vancomycin) to achieve bactericidal synergy, the choice of aminoglycoside must be based on special in vitro susceptibility testing. Susceptibility only to high levels of aminoglycosides in vitro predicts synergy when low-dose aminoglycoside therapy is combined with a cell wall–active drug. If the strain is susceptible to high levels of gentamicin and streptomycin, gentamicin is preferred because serum levels can be readily determined and toxicity is less. High-level enterococcal resistance to gentamicin in vitro does not rule out susceptibility of these strains to high levels of streptomycin; in such cases, streptomycin should be used if these strains are susceptible to high levels of streptomycin.

Few therapeutic options are available for endocarditis due to enterococci that are resistant to high levels of gentamicin and streptomycin; no synergistic cell wall–active drug/aminoglycoside combination exists for endocarditis due to such strains, but the combination of the cell wall–active drugs ampicillin and ceftriaxone has recently been shown to be effective and minimizes the risk of nephrotoxicity. Many clinicians have begun to use ampicillin plus ceftriaxone rather than ampicillin plus gentamicin for Enterococcus faecalis endocarditis, even for strains without aminoglycoside resistance, because efficacy is similar and toxicity is less.

Because of toxicity, neomycin is limited to topical use in small amounts. Neomycin is available for eye, ear, oral, and rectal use and as a bladder irrigant. Oral neomycin is used topically against intestinal microbiota to prepare the bowel before surgery and to treat hepatic coma.

Contraindications to Aminoglycosides

Aminoglycosides are contraindicated in patients who are allergic to them.

Use During Pregnancy and Breastfeeding

With aminoglycosides, there is evidence of risk to the fetus (eg, auditory toxicity), but clinical benefits may outweigh risk. If an aminoglycoside is used during pregnancy or if the patient becomes pregnant while taking an aminoglycoside, she should be apprised of the potential hazard to the fetus.

Aminoglycosides enter breast milk but are not well absorbed orally. Thus, they are considered compatible with use during breastfeeding.

Adverse Effects of Aminoglycosides

All aminoglycosides cause

  • Renal toxicity (often reversible)

  • Vestibular and auditory toxicity (often irreversible)

  • Prolongation of effects of neuromuscular blockers

Symptoms and signs of vestibular damage are vertigo and ataxia.

Risk factors for renal, vestibular, and auditory toxicity are

  • Frequent or very high doses

  • Very high blood levels of the drug

  • Long duration of therapy (particularly > 3 days)

  • Older age

  • A preexisting renal disorder

  • Coadministration of vancomycin, cyclosporine, amphotericin B, iodinated contrast agents, or other nephrotoxins

  • For auditory toxicity, a genetic predisposition, preexisting hearing problems, and coadministration of loop diuretics

High doses given over a long period of time typically cause more concern about renal toxicity, but even low doses given for a short time can worsen renal function.

Patients receiving aminoglycosides for > 2 weeks and those at risk of vestibular and auditory toxicity should be monitored with serial audiography. At the first sign of toxicity, the drug should be stopped (if possible), or dosing should be adjusted.

Aminoglycosides can prolong the effect of neuromuscular blockers (eg, succinylcholine, curare-like drugs) and worsen weakness in disorders affecting neuromuscular transmission (eg, myasthenia gravis). These effects are particularly likely when the drug is given too rapidly or serum levels are excessively high. The effects sometimes resolve more rapidly if patients are given neostigmine or IV calcium. Other neurologic effects include paresthesias and peripheral neuropathy.

Hypersensitivity reactions are uncommon except for contact dermatitis due to topical neomycin. High oral doses of neomycin can cause malabsorption.

Dosing Considerations for Aminoglycosides

Because toxicity depends more on duration of therapeutic levels than on peak levels and because efficacy is concentration-dependent Time vs concentration of a single dose of a theoretical antibiotic Time vs concentration of a single dose of a theoretical antibiotic rather than time-dependent, frequent doses are avoided. Once/day IV dosing is preferred over traditional intermittent dosing for most indications. Once/day dosing may not be preferred when used for gram-positive synergy (eg, enterococcal endocarditis) or in patients who are pregnant, have significant burns (> 20% of body surface area), or have renal failure (creatinine clearance < 40 mL/minute). IV aminoglycosides are typically infused over 30 to 60 minutes.

If a patient is below their ideal body weight (IBW), their total body weight (TBW) should be used to calculate doses. If TBW is greater than IBW but less than 120% of IBW, dosing should be based on IBW. If TBW is greater than 120% of IBW, adjusted body weight (ABW) should be used to calculate doses:

  • IBW in kg (males): 50 + (2.3 × inches above 60 inches)

  • IBW in kg (females): 45.5 + (2.3 × inches above 60 inches)

  • ABW in kg: IBW + [0.4 × (TBW – IBW)]

In patients with normal renal function, once/day dosing is

  • Gentamicin or tobramycin: 5 mg/kg (7 mg/kg if patients are critically ill) every 24 hours

  • Amikacin: 15 mg/kg every 24 hours

If patients respond to the 7-mg/kg dose of gentamicin or tobramycin clinically and renal function continues to be normal, the once/day dose can be reduced to 5 mg/kg after the first few days of treatment.

In critically ill patients, peak serum levels should be determined after the first dose. In all patients, peak and trough levels are measured after the 2nd or 3rd dose (when the daily dose is divided) or when therapy lasts > 3 days, as well as after the dose is changed. Serum creatinine is measured every 2 to 3 days, and if it is stable, serum aminoglycoside levels do not need to be measured again. Peak concentration is the level 60 minutes after an IM injection or 30 minutes after the end of a 30-minute IV infusion. Trough levels are measured during the 30 minutes before the next dose.

With once/day dosing, peak levels in serum of at least 10 times the minimum inhibitory concentration (MIC) are desirable. This desired peak level is typically 15 to 20 mcg/mL for gentamicin (31.35 to 41.80 micromol/L) and tobramycin (32.08 to 42.78 micromol/L). Dosing is adjusted to ensure a therapeutic peak serum level (to facilitate concentration-dependent activity) and nontoxic trough levels. In critically ill patients, who are likely to have expanded volumes of distribution and who are given higher initial doses, target peak serum levels are 16 to 24 mcg/mL for gentamicin (33.44 to 50.16 micromol/L) and tobramycin (34.22 to 51.34 micromol/L) and 56 to 64 mcg/mL (95.65 to 109.31 micromol/L) for amikacin. For gentamicin and tobramycin, trough levels should be < 1 mcg/mL (< 2.09 micromol/L for gentamicin and < 2.14 micromol/L for tobramycin) at 18 to 24 hours after the first dose with once/day dosing and between 1 and 2 mcg/mL (between 2.09 and 4.18 micromol/L for gentamicin and between 2.14 and 4.28 micromol/L for tobramycin) with traditional intermittent dosing.

For patients with renal insufficiency on traditional intermittent dosing, the loading dose is the same as that for patients with normal renal function; usually, the dosing interval is increased rather than the dose decreased. Guidelines for maintenance doses based on serum creatinine or creatinine clearance values are available (see table Traditional Intermittent Dosing for Aminoglycosides in Adults Dosing for Aminoglycosides in Adults Dosing for Aminoglycosides in Adults ), but they are not precise, and measurement of blood levels is preferred.

If patients are taking a high dose of a beta-lactam and an aminoglycoside, the high serum levels of the beta-lactam can inactivate the aminoglycoside in vitro in serum specimens obtained to determine drug levels unless the specimen is assayed immediately or frozen. If patients with renal failure are concurrently taking an aminoglycoside and a high-dose beta-lactam, the serum aminoglycoside level may be lower because interaction in vivo is prolonged.


Drugs Mentioned In This Article

Drug Name Select Trade
AK-Tob, BETHKIS, Kitabis Pak, Nebcin, Tobi, TOBI Podhaler, Tobrasol , Tobrex
Garamycin, Genoptic, Genoptic SOP, Gentacidin, Gentafair, Gentak , Gentasol, Ocu-Mycin
Amikin, Amikin Pediatric, ARIKAYCE
No brand name available
FIRVANQ, Vancocin, Vancocin Powder, VANCOSOL
Ceftrisol Plus, Rocephin
Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia, Vevye
Amphocin, Fungizone
Anectine, Quelicin
BLOXIVERZ, Prostigmin
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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