Aminoglycosides Antibiotics

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Questions and Answers

Which mechanism primarily contributes to bacterial resistance against aminoglycosides?

  • Increased production of bacterial cell wall porins preventing aminoglycoside entry.
  • Enzymatic degradation of aminoglycosides within the bacterial cytoplasm.
  • Mutation of mRNA start codon (AUG) to prevent drug binding.
  • Methylation of the ribosome binding site, hindering aminoglycoside attachment. (correct)

A patient with Pseudomonas aeruginosa pneumonia is being treated with tobramycin. Therapeutic drug monitoring reveals a peak concentration of 2 mcg/mL and a trough concentration of 1 mcg/mL. How should the tobramycin dose be adjusted?

  • Decrease the dose and increase the frequency to minimize nephrotoxicity.
  • Increase the dose to achieve a peak level of 4-10 mcg/mL to enhance efficacy. (correct)
  • Maintain the current dose because the trough level is within range.
  • Discontinue tobramycin and switch to an alternative antibiotic due to potential resistance.

Why is it beneficial to administer an aminoglycoside, like gentamicin, in combination with a penicillin for certain infections?

  • Penicillins alter the bacterial cell wall, enhancing aminoglycoside penetration into the cell. (correct)
  • Penicillins enhance aminoglycoside activity by directly inhibiting bacterial ribosome function.
  • Penicillins reduce the nephrotoxic potential of aminoglycosides.
  • Penicillins prevent the development of bacterial resistance to aminoglycosides.

Which of the following is the mechanism of action of aminoglycosides that leads to bacterial cell death?

<p>Blockage of peptide chain translocation and misreading of mRNA during translation. (A)</p> Signup and view all the answers

A patient is receiving aminoglycoside therapy. Which pre-existing condition would be of greatest concern when considering the potential adverse effects of this medication?

<p>Myasthenia gravis. (D)</p> Signup and view all the answers

Flashcards

Aminoglycosides Mechanism

Block translocation of the peptide chain and cause misreading of mRNA, leading to cell death. They bind to the 30S ribosomal subunit, causing misreading and premature termination of translation.

Aminoglycosides Spectrum of Activity

Primarily effective against gram-negative bacteria, including E. coli, Klebsiella pneumoniae, H. influenzae, Pseudomonas, and others. Synergistic activity with vancomycin and penicillin against some gram-positive bacteria.

Aminoglycosides Side Effects

Nephrotoxicity, ototoxicity, neuromuscular blockade (especially in critically ill patients), and teratogenicity.

Aminoglycosides Resistance

Methylation of the ribosome binding site and decreased permeation to the target due to active efflux.

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Aminoglycosides Special Uses

Penicillins enhance aminoglycoside penetration, tobramycin inhalation treats Pseudomonas in cystic fibrosis patients. Target peak levels of 4-10 mcg/mL and trough levels of 0.5-2 mcg/mL for serious infections.

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Study Notes

  • Aminoglycosides are a class of antibiotics that includes gentamycin, amikacin, tobramycin, neomycin, and streptomycin.

Mechanism of Action

  • Aminoglycosides block the translocation of the peptide chain and cause misreading of mRNA, leading to cell death.
  • They bind to the 30S subunit at the start codon (AUG) of mRNA, causing the ribosome to assemble incorrectly.
  • This "misreading" of mRNA results in the wrong amino acids being added or incorrect initiation of translation.
  • Premature termination of translation can occur due to the misreading of mRNA, leading to incomplete protein chains.
  • Abnormal ribosomal complexes, known as streptomycin monosomes, can form, which are nonfunctional units that can't continue translation properly.
  • Mistranslated proteins are nonfunctional or abnormal, disrupting cellular processes and causing toxic effects, contributing to cell damage or death (bactericidal, concentration-dependent).

Special Uses

  • Often used in combination with penicillins, which alter the cell wall and enhance aminoglycoside penetration.
  • Tobramycin inhalation is used for cystic fibrosis patients who acquire Pseudomonas infections.
  • Target peak levels for tobramycin and gentamicin are 4 - 10 mcg/mL depending on the infection.
  • Target trough levels for tobramycin and gentamicin are 0.5 - 2 mcg/mL for serious infections.

Spectrum of Activity

  • Primarily effective against gram-negative bacteria, including BLP (beta-lactamase-producing) E. coli, Klebsiella pneumoniae, H. influenzae, SPACE organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter), ESBL (Extended Spectrum Beta-Lactamase producers), CRE (Carbapenem-resistant Enterobacteriaceae), and Pseudomonas.
  • It has synergistic activity against Staphylococcus, Streptococcus, or Enterococcus species when combined with vancomycin and penicillin.

Resistance

  • Resistance can occur through methylation of the ribosome binding site.
  • Decreased permeation to the target site due to active efflux.

Side Effects

  • Can cause nephrotoxicity, especially when used with other nephrotoxic agents like cyclosporine, cisplatin, NSAIDs, and vancomycin.
  • May lead to ototoxicity, particularly with diuretics.
  • Can cause neuromuscular blockade in critically ill patients (contraindicated in myasthenia gravis).
  • Is teratogenic.

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