Aminoglycoside Ototoxicity Risk Factors and Prevention

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Which aminoglycoside has the broadest spectrum of activity?

Paromomycin

Gentamicin (correct)

Streptomycin

Framycetin

What contributes to the basic nature of aminoglycoside antimicrobials?

The chemical structure of apramycin

The aminocyclitol group

Hydroxyl groups on the sugar moieties

Amino sugars attached to the aminocyclitol ring (correct)

Which aminoglycoside has synergistic activity toward selected gram-positive organisms?

Neomycin (correct)

Kanamycin

Amikacin

Tobramycin

What is characteristic of the chemical structure of aminoglycosides?

Amino sugars attached to the aminocyclitol ring in glycosidic linkage Signup and view all the answers

What is the recommended method for obtaining evidence-based withdrawal recommendations for apramycin in the US?

Contacting the Food Animal Residue Avoidance Databank (FARAD) Signup and view all the answers

What is the elimination half-life of apramycin in calves?

~4–5 hours Signup and view all the answers

How is apramycin primarily excreted from the body?

Unchanged in the urine Signup and view all the answers

What is the recommended dosage of apramycin for swine?

22.5 mg/kg, PO, every 24 hours for 7 consecutive days Signup and view all the answers

How does spectinomycin primarily interfere with bacteria?

Interferes with protein synthesis Signup and view all the answers

What percentage of spectinomycin can be recovered unchanged in the urine over 24–48 hours?

~80% Signup and view all the answers

What is the main site of action for aminoglycosides?

Bacterial ribosome Signup and view all the answers

What effect does low oxygen tension have on the efficacy of aminoglycosides?

Diminishes their transfer into bacteria Signup and view all the answers

Which type of microorganisms are aminoglycosides principally effective against?

Gram-negative organisms Signup and view all the answers

What is the pKa range of aminoglycoside drugs?

8-10 Signup and view all the answers

What is the driving force for the transfer of aminoglycosides into bacteria?

Membrane potential Signup and view all the answers

In what environment is the efficacy of aminoglycosides markedly curtailed?

Anaerobic environment Signup and view all the answers

What process is required for aminoglycosides to reach the bacterial ribosome?

Active transport process Signup and view all the answers

What can interfere with the transport of aminoglycosides into bacteria?

Divalent cations located in the LPS, cell wall, or membrane Signup and view all the answers

Which type of antimicrobials commonly demonstrate synergism when used in combination with aminoglycosides?

Beta-lactams (penicillins and cephalosporins) Signup and view all the answers

What effect does an alkaline pH have on the passive movement of aminoglycosides across bacterial cell membranes?

Facilitates it Signup and view all the answers

Which ribosomal subunit is irreversibly bound by aminoglycosides?

30S subunit Signup and view all the answers

Which type of organisms can aminoglycosides be less effective against at low concentrations?

Gram-positive organisms Signup and view all the answers

What is the main reason aminoglycosides are relatively ineffective against facultative anaerobes in a low-oxygen environment?

Oxygen is necessary for active transport of the drug into the microbe. Signup and view all the answers

What is the main factor that leads to indirectly proportional changes in the concentration of an aminoglycoside?

Dehydration Signup and view all the answers

In which body compartment do aminoglycosides accumulate as ionization increases?

Extracellular fluid Signup and view all the answers

What is the main reason for administering aminoglycosides via once-daily treatment?

To minimize adaptive resistance Signup and view all the answers

Why are aminoglycosides contraindicated for short dosing intervals, including continuous infusions?

To minimize adaptive resistance Signup and view all the answers

What is the main reason that aminoglycosides are relatively ineffective against obligate anaerobic bacteria and fungi?

Lack of active transport into the microbe in low-oxygen environments Signup and view all the answers

What is the main route of excretion for aminoglycosides?

Via glomerular filtration in the kidneys Signup and view all the answers

In which body compartment do aminoglycosides reach therapeutic concentrations?

In the synovial, pleural, and peritoneal fluids Signup and view all the answers

What is the most common method of administering aminoglycosides?

Slow intramuscular injection Signup and view all the answers

What complication may arise from excessive accumulation of aminoglycosides in tubular cells?

Tubular cell necrosis Signup and view all the answers

What is the main reason that once-daily treatment with aminoglycosides is indicated?

To prevent adaptive resistance Signup and view all the answers

Which of the following is a mechanism of resistance to aminoglycoside antimicrobials that is plasmid or chromosomally mediated?

Increased production of outer cell membrane protein, H1 Signup and view all the answers

In which bacterial species does impaired transport across the cell membrane occur as a mechanism of nonplasmid-mediated resistance to aminoglycosides?

Clostridium perfringens Signup and view all the answers

Which of the following is a characteristic of streptomycin and dihydrostreptomycin?

Resistance limited by narrow spectra Signup and view all the answers

Under which condition will the efficacy of aminoglycosides be reduced?

Decreased pH Signup and view all the answers

What is the most frequently observed phenomenon in P aeruginosa and other gram-negative bacilli, where bacterial cells develop a reversible resistance to aminoglycosides if they survive the initial ionic binding?

Adaptive resistance Signup and view all the answers

Which aminoglycoside has the broadest spectrum among the group?

Amikacin Signup and view all the answers

Which bacteria are still susceptible to streptomycin and dihydrostreptomycin?

Actinomyces bovis and Pasteurella spp Signup and view all the answers

What happens to adaptive resistance after multiple daily dosing or constant rate infusions?

It persists Signup and view all the answers

What is the effect of once-daily dosing on adaptive resistance?

It reduces adaptive resistance Signup and view all the answers

Which mechanism of resistance increases in P aeruginosa mutants, resulting in resistance to gentamicin?

Increased production of outer cell membrane protein, H1 Signup and view all the answers

Which bacterial species are sensitive to streptomycin?

Mycobacterium tuberculosis, Salmonella spp, E coli, Proteus spp, and Acinetobacter spp Signup and view all the answers

What is the most common route of excretion for aminoglycosides?

Renal excretion Signup and view all the answers

Which phase of elimination reflects the gradual release of the antimicrobial from renal intracellular binding sites?

Gamma phase Signup and view all the answers

What is the recommended peak concentration of aminoglycosides for efficacy?

$10-12$ times the MIC Signup and view all the answers

What is the ideal time to collect a trough concentration for safety monitoring?

Just before the next dose Signup and view all the answers

How should the dosage regimen of aminoglycosides be altered to minimize nephrotoxicity?

By administering lower doses at more frequent intervals Signup and view all the answers

In cases of renal failure, what should be done with the treatment interval for aminoglycosides?

It should be increased Signup and view all the answers

What is the recommended action if plasma creatinine concentrations are increased in cases of renal failure?

Increase the treatment interval Signup and view all the answers

What should be done to assure that 10 times the MIC is achieved at peak concentrations?

Increase the dose rate and frequency Signup and view all the answers

What is the preferred number of time points to monitor when administering aminoglycosides intravenously?

$2$ time points (peak and trough concentrations) Signup and view all the answers

When should trough concentrations generally be collected?

Just before the next dose Signup and view all the answers

What is the most common method of excretion for aminoglycosides?

Renal excretion Signup and view all the answers

What factor determines how half-life will vary?

Volume of the extracellular fluid compartment Signup and view all the answers

What is the order of aminoglycosides from most ototoxic to least ototoxic?

Gentamicin, sisomicin, neomycin, netilmicin Signup and view all the answers

Which drug has been shown to decrease the risk of aminoglycoside ototoxicity in people?

N-acetylcysteine Signup and view all the answers

What is the effect of aminoglycosides on muscle weakness and respiratory arrest?

Causes muscle weakness and respiratory arrest Signup and view all the answers

What is the mechanism behind the neuromuscular blockade caused by aminoglycosides?

Competitive inhibition of acetylcholine release Signup and view all the answers

Which drug antagonizes the neuromuscular blockade caused by aminoglycosides?

Neostigmine Signup and view all the answers

What adverse effect may be aggravated by aminoglycosides when administered to animals under halothane anesthesia?

Cardiovascular depression Signup and view all the answers

What laboratory finding is a noteworthy adverse effect associated with aminoglycosides?

Proteinuria Signup and view all the answers

What happens if aminoglycosides are administered with loop-acting diuretics, especially furosemide?

Enhanced nephrotoxicity Signup and view all the answers

What do high concentrations of carbenicillin, ticarcillin, and piperacillin do to aminoglycosides?

Inactivate them Signup and view all the answers

Which of the following is true about withdrawal intervals for aminoglycosides in production animals?

Aminoglycosides are not prohibited from extralabel use in production animals in the US. Signup and view all the answers

Which can enhance the antibacterial efficacy of aminoglycosides?

Beta-lactam antimicrobials Signup and view all the answers

What should veterinarians be aware of regarding the withdrawal times for aminoglycosides used in an extralabel fashion in production animals?

Withdrawal times vary depending on the specific drug used. Signup and view all the answers

What is the primary concern associated with aminoglycoside nephrotoxicity?

Renal failure due to acute tubular necrosis Signup and view all the answers

How can nephrotoxicity be detected in animals undergoing aminoglycoside treatment?

Increased fractional sodium excretion Signup and view all the answers

What role does mitochondria play in aminoglycoside-induced ototoxicity?

Prominent role in ototoxicity Signup and view all the answers

Which animals are particularly sensitive to the toxic vestibular effects of aminoglycosides?

Cats Signup and view all the answers

What characteristic reflects permanent damage and loss of the hair cells in the organ of Corti due to aminoglycoside-induced ototoxicity?

Loss of high-frequency hearing Signup and view all the answers

In renal insufficiency, what alteration is generally made to the interval between doses of aminoglycosides?

Prolonged interval Signup and view all the answers

What is the driving force for the transfer of aminoglycosides into proximal tubular epithelial cells?

Active uptake due to lower pH Signup and view all the answers

What should be considered for treatment to minimize aminoglycoside nephrotoxicity?

[N-acetylcysteine] treatment Signup and view all the answers

What is necessary for kidneys to eliminate accumulated aminoglycosides?

Drug-free period before next dose Signup and view all the answers

What is indicative of aminoglycoside nephrotoxicity based on laboratory tests?

Increased BUN and creatinine concentrations Signup and view all the answers

In cases of excessive accumulation, what complication may arise from aminoglycosides in tubular cells?

Tubular necrosis and injury Signup and view all the answers

What contributes to the reduction of toxicity and negative impact on efficacy while treating renal insufficiency with aminoglycosides?

Decreasing plasma drug concentrations below recommended levels Signup and view all the answers