Aminoglycoside

What are Aminoglycosides?

Aminoglycosides are a class of antibiotics used mainly in the treatment of aerobic gram-negative bacilli infections, although they are also effective against other bacteria including Staphylococci and Mycobacterium tuberculosis. They are often used in combination with other antibiotics.

Aminoglycosides are thought to work by inhibiting protein synthesis inside bacteria. Kill rates of bacteria are increased when higher concentrations of aminoglycosides are present; however, the margin between a safe and a toxic dose is narrow and monitoring is often needed, although once daily dosing increases the safety window. Impairment of kidney function and hearing loss are the most common side effects of aminoglycosides. Aminoglycosides tend to be used when other less toxic antibiotics are contraindicated or ineffective.

Aminoglycosides are not well absorbed when given by mouth, so need to be given by injection by healthcare personnel.

What are aminoglycoside antibiotics used to treat?

Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis.

 Aminoglycosides are used for

• Serious gram-negative bacillary infections (especially those due to Pseudomonas aeruginosa)

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; however, some gram-negative bacilli and methicillin-resistant 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 and tularemia. They are usually used with a broad-spectrum β-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, or 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-sensitive P. aeruginosa is identified.

Gentamicin or, less commonly, streptomycin may be used with other antibiotics to treat 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.

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.

Streptomycin has limited uses because of resistance and toxicity. It is used to treat tularemia and plague and, with other antibiotics, to treat TB.

Because of toxicity, neomycin and kanamycin are 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 flora to prepare the bowel before surgery and to treat hepatic coma.