Aminoglycosides

Aminoglycosides

Aminoglycosides provide effective bactericidal activity against:

• gram-negative bacilli
• some aerobic gram-positive bacteria
• mycobacteria
• some protozoa.

Common aminoglycosides

Aminoglycosides currently in use include:

• amikacin sulfate
• gentamicin sulfate
• kanamycin sulfate
• neomycin sulfate
• paromomycin sulfate
• streptomycin sulfate
• tobramycin sulfate.

Pharmacokinetics (how drugs circulate)

Because aminoglycosides are absorbed poorly from the GI tract, they’re usually given parenterally. After I.V. or I.M. administration, aminoglycoside absorption is rapid and complete.

Distribution

Aminoglycosides are distributed widely in extracellular fluid. They readily cross the placental barrier, but don’t cross the blood-brain barrier.

Metabolism and excretion

Aminoglycosides aren’t metabolized. They’re excreted primarily unchanged by the kidneys.

 

Pharmacodynamics (how drugs act)

Aminoglycosides act as bactericidal drugs (remember, this means they kill bacteria) against susceptible organisms by binding to the bacterium’s 30S subunit, a specific ribosome in the microorganism, thereby interrupting protein synthesis and causing the bacterium to die.

Rising resistance

Bacterial resistance to aminoglycosides may be related to:

• failure of the drug to cross the cell membrane
• altered binding to ribosomes
• destruction of the drug by bacterial enzymes.

One-two punch

Some gram-positive enterococci resist aminoglycoside transport across the cell membrane. When penicillin is used with aminoglycoside therapy, the cell wall is altered, allowing the aminoglycoside to penetrate the bacterial cell.

 

Pharmacotherapeutics (how drugs are used)

Aminoglycosides are most useful in treating:

• infections caused by gram-negative bacilli
• serious nosocomial (hospital-acquired) infections, such as gram-negative bacteremia (abnormal presence of microorganisms in the bloodstream), peritonitis (inflammation of the peritoneum, the membrane that lines the abdominal cavity), and pneumonia, in critically ill patients
• urinary tract infections (UTIs) caused by enteric bacilli that are resistant to less toxic antibiotics, such as penicillins and cephalosporins
• infections of the central nervous system (CNS) and the eye (treated with local instillation).

Works well with others

Aminoglycosides are used in combination with penicillins to treat gram-positive organisms, such as staphylococcal or enterococcal

infections. Combination therapy increases the drugs’ effectiveness.

Warning!

Adverse reactions to aminoglycosides

Serious adverse reactions limit the use of aminoglycosides. They include:

• neuromuscular reactions, ranging from peripheral nerve toxicity to neuromuscular blockade
• ototoxicity
• renal toxicity.

Oral history

Adverse reactions to oral aminoglycosides include:

• nausea and vomiting
• diarrhea.

Inactive duty

Aminoglycosides are inactive against anaerobic bacteria.

Role call

Individual aminoglycosides may have their own particular usefulness:

• Streptomycin is active against many strains of mycobacteria, including Mycobacterium tuberculosis, and against the gram-positive bacteria Nocardia and Erysipelothrix.
• Amikacin, gentamicin, and tobramycin are active against Acinetobacter, Citrobacter, Enterobacter, Klebsiella, Proteus (indole-positive and indole-negative), Providencia, Serratia, Escherichia coli, and Pseudomonas aeruginosa.

Drug interactions

Carbenicillin and ticarcillin reduce the effects of amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin. This is especially true if the penicillin and aminoglycoside are mixed in the same container or I.V. line.

Putting up a blockade

Amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin administered with neuromuscular blockers increase neuromuscular blockade, resulting in increased muscle relaxation and respiratory distress.

Kidney punch

Toxicity to the kidneys may result in renal failure; toxicity to the neurologic system results in peripheral neuropathy with numbness and tingling of the extremities. The risk of renal toxicity also increases when amikacin, gentamicin, kanamycin, or tobramycin is taken with cyclosporine, amphotericin B, or acyclovir.

What? Say that again…

The symptoms of ototoxicity (damage to the ear) caused by aminoglycosides may be masked by antiemetic drugs. Loop diuretics taken with aminoglycosides increase the risk of ototoxicity. Hearing loss may occur in varying degrees and may be irreversible.