Aminoglycosides: Definition, Pharmacology, Clinical Uses and Resistance
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 loveallfind.com are often used in combination with other antibiotics. Aminoglycosides are infrequently used alone, except when used for plague and 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.
Objective: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years. Design: retrospective multicenter study. Setting: hospital department, rehabilitation, long-term care center. Results: patients, mean age: One hundred and twenty-seven patients received other nephrotoxic drug s.
Average treatment period was 2. The monitoring of maximal plasmatic concentration Cmax was done in 37 patients, 9 of them had probabilistic treatment. Conclusion: aminoglycosides dosing used in elderly patients probably need therapeutic drug monitoring and dose adjustment. Aminoglycosides are used to treat severe infections.
One of the most important side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity, short treatments are necessary and avoiding others nephrotoxic drugs could be relevant. Keywords: aminoglycoside; oldest old; renal failure. All rights reserved. For Permissions, please email: journals. Abstract Objective: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years. Publication types Multicenter Study Observational Study.
Substances Aminoglycosides Anti-Bacterial Agents.
Clinical uses and toxicities
Oct 20, · Because aminoglycosides are normally used to treat serious infections, they are typically administered into the veins of the body (intravenously, or IV). However, some aminoglycosides can be . The aminoglycosides are natural products and semisynthetic derivatives from a variety of actinomycetes and have potent activity against many gram negative bacteria. The first aminoglycoside used in clinical practice was streptomycin which was derived from Streptomyces griseus and was the first effec . Aminoglycoside, any of several natural and semisynthetic compounds that are used to treat bacterial loveallfind.com term aminoglycoside is derived from the chemical structure of these compounds, which are made up of amino groups (?NH 2) attached to glycosides (derivatives of sugar).The first aminoglycoside, the antibiotic streptomycin, was discovered in by American biochemists .
The gentamycin is the most commonly used aminoglycoside, amikacin but may be particularly effective against resistant organisms. Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis , especially against endocarditis.
Resistance is rare but increases in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially nephrotoxic agents decreases the risk of toxicity. The single daily dosage of aminoglycosides is possible due to its rapid death dependent on the concentration and the effect subsequent to antibiotics, and has the potential to decrease toxicity.
The single daily dose of aminoglycosides appears to be safe, effective and cost-effective. In certain clinical situations, such as patients with endocarditis or pediatric patients, the traditional traditional dosage is still generally recommended.
The first aminoglycoside, streptomycin, was isolated from Streptomyces griseus in Neomycin, isolated from Streptomyces fradiae, had better activity than streptomycin against aerobic gram-negative bacilli but, due to its formidable toxicity, could not be used systemically in a safe manner.
Gentamicin, isolated from Micromonospora in , was a breakthrough in the treatment of gram-negative bacillary infections, including those caused by Pseudomonas aeruginosa. Subsequently, other aminoglycosides were developed, including amikacin Amikin , netilmicin Netromycin and tobramycin Nebcin , all currently available for systemic use in the United States. Despite the introduction of newer, less toxic antimicrobial agents, aminoglycosides continue to play a useful role in the treatment of serious bacterial infections and serious enterococci.
Traditionally, it was believed that the antibacterial properties of aminoglycosides were the result of the inhibition of bacterial protein synthesis by irreversible binding to the 30S bacterial ribosome. However, this explanation does not take into account the potent bactericidal properties of these agents, since other antibiotics that inhibit the synthesis of proteins such as tetracycline are not bactericidal.
Recent experimental studies show that the initial site of action is the outer bacterial membrane. Cationic antibiotic molecules create fissures in the outer cell membrane, resulting in leakage of intracellular content and improved absorption of antibiotics.
This rapid action on the outer membrane probably accounts for most of the bactericidal activity. Anaerobes have less energy available for this absorption, so aminoglycosides are less active against anaerobes. Aminoglycosides are poorly absorbed from the gastrointestinal tract. After parenteral administration, the aminoglycosides are distributed mainly within the extracellular fluid. Therefore, the presence of disease states or iatrogenic situations that alter the fluid balance may require dosage modifications.
When used parenterally, adequate drug concentrations are typically found in bone, synovial fluid, and peritoneal fluid. Penetration of biological membranes is poor due to the polar structure of the drug, and intracellular concentrations are usually low, with the exception of the proximal renal tubule.
Endotracheal administration results in higher bronchial levels compared to systemic administration, but differences in clinical outcome have not been consistent. After parenteral administration of an aminoglycoside, subtherapeutic concentrations are usually found in the cerebrospinal fluid, vitreous fluid, prostate, and brain. The half-life of the aminoglycosides in the renal cortex is approximately hours, so that repetitive dosing can cause renal accumulation and toxicity.
Aminoglycosides exhibit bactericidal, concentration-dependent killing action and are active against a broad range of aerobic gram-negative bacilli. They are also active against staphylococci and certain mycobacteria. Aminoglycosides are effective even when the bacterial inoculum is large and resistance rarely develops during the course of treatment.
These potent antimicrobials are used as prophylaxis and treatment in a variety of clinical situations. Gentamicin is the aminoglycoside that is used most frequently due to its low cost and reliable activity against gram-negative aerobes. However, local resistance patterns should influence the choice of therapy. In general, gentamicin, tobramycin and amikacin are used in similar circumstances, often interchangeably. Tobramycin may be the aminoglycoside of choice for use in another because it has shown greater in vitro activity.
However, the clinical importance of this activity has been questioned. Amikacin is particularly effective when used against bacteria that are resistant to other aminoglycosides, since its chemical structure makes it less susceptible to inactive enzymes.
Depending on local resistance patterns, amikacin may be the preferred agent for serious nosocomial infections caused by gram-negative bacilli. Most resistance to aminoglycosides is caused by bacterial inactivation by intracellular enzymes. Due to structural differences, amikacin is not inactivated by the common enzymes that inactivate gentamicin and tobramycin.
Therefore, a large proportion of gram-negative aerobes that are resistant to gentamicin and tobramycin are sensitive to amikacin. In addition, with greater use of amikacin, a lower incidence of resistance has been observed compared to an increased use of gentamicin and tobramycin. Aeruginosa may show adaptive resistance to aminoglycosides.
This occurs when previously susceptible populations become less susceptible to the antibiotic as a result of decreased intracellular concentrations of the antibiotic.
This decrease may result in colonization, slow clinical response or failure of the antibiotic despite the sensitivity in in vitro tests. Aminoglycosides are often combined with a beta-lactam drug in the treatment of Staphylococcus aureus infection. This combination increases bactericidal activity, whereas monotherapy with aminoglycosides can allow resistant staphylococci to persist during treatment and cause a clinical relapse once the antibiotic is stopped. The infectious endocarditis is due to enterococci with high levels of resistance to aminoglycosides is becoming more common.
All enterococci have a low level resistance to aminoglycosides due to their anaerobic metabolism. In the treatment of bacterial endocarditis, a beta-lactam drug is also used synergistically to facilitate the penetration of aminoglycosides into the cell. When high level resistance occurs, it is usually due to the production of inactivating enzymes by bacteria. Due to the increasing frequency of this resistance, all enterococci must be analyzed to detect susceptibility to antibiotics.
As with all antibiotics, resistance to aminoglycosides is increasingly prevalent. The repeated use of aminoglycosides, especially when a single type is used, leads to a higher incidence of resistance. However, resistance to aminoglycosides requires long periods of exposure or inocula of very large organisms and occurs less frequently than with other agents, such as the third -generation of cephalosporins, which are also effective against gram-negative organisms.
She specializes in family medicine. They are potent bactericidal antibiotics that act by creating fissures in the external membrane of the bacterial cell and are particularly active against aerobic bacteria. About The Author Dr. Cameron Troup MD Dr. No comments yet Leave Comments Cancel reply.