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What is the primary mechanism of action for aminoglycosides?
What is the primary mechanism of action for aminoglycosides?
Which of the following is a common mechanism by which bacteria develop resistance to aminoglycosides?
Which of the following is a common mechanism by which bacteria develop resistance to aminoglycosides?
In relation to antibiotic treatment, what does the term 'post-antibiotic effect' (PAE) refer to?
In relation to antibiotic treatment, what does the term 'post-antibiotic effect' (PAE) refer to?
What is the recommended target concentration (Cmax) for aminoglycosides in relation to the minimum inhibitory concentration (MIC)?
What is the recommended target concentration (Cmax) for aminoglycosides in relation to the minimum inhibitory concentration (MIC)?
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Which of the following describes aminoglycosides in terms of their effectiveness?
Which of the following describes aminoglycosides in terms of their effectiveness?
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What is a significant risk associated with the use of gentamicin?
What is a significant risk associated with the use of gentamicin?
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Which of the following is NOT a common use for gentamicin?
Which of the following is NOT a common use for gentamicin?
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What is the primary purpose of Therapeutic Drug Monitoring (TDM) when using gentamicin?
What is the primary purpose of Therapeutic Drug Monitoring (TDM) when using gentamicin?
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Which of the following bacteria is amikacin particularly effective against due to its resistance to enzymes?
Which of the following bacteria is amikacin particularly effective against due to its resistance to enzymes?
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Which type of administration is NOT associated with gentamicin?
Which type of administration is NOT associated with gentamicin?
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What is a major advantage of tobramycin compared to gentamicin?
What is a major advantage of tobramycin compared to gentamicin?
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What potential side effect of gentamicin can lead to permanent hearing loss?
What potential side effect of gentamicin can lead to permanent hearing loss?
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Which of the following bacteria are aminoglycosides effective against?
Which of the following bacteria are aminoglycosides effective against?
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What is a significant adverse effect associated with aminoglycosides when used for prolonged periods?
What is a significant adverse effect associated with aminoglycosides when used for prolonged periods?
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What is the route of administration for most aminoglycosides due to poor absorption?
What is the route of administration for most aminoglycosides due to poor absorption?
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Which factor increases the risk of nephrotoxicity when taking aminoglycosides?
Which factor increases the risk of nephrotoxicity when taking aminoglycosides?
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Which of the following combinations is an acceptable use for streptomycin?
Which of the following combinations is an acceptable use for streptomycin?
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For which condition is streptomycin primarily used as a second-line agent?
For which condition is streptomycin primarily used as a second-line agent?
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What is a potential effect of aminoglycosides on pregnant women?
What is a potential effect of aminoglycosides on pregnant women?
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What is required for aminoglycoside use in patients with renal impairment?
What is required for aminoglycoside use in patients with renal impairment?
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Study Notes
Aminoglycosides
- Bactericidal antibiotics targeting bacterial ribosomes (30S subunit).
- Broad spectrum, mostly bacteriostatic; resistance is common.
- Used for serious infections caused by aerobic gram-negative bacilli (bacteremia, sepsis, endocarditis, tuberculosis).
- Often combined with vancomycin/penicillin.
- Serious toxicities possible; safer alternatives exist (cephalosporins, fluoroquinolones, carbapenems).
- Therapeutic drug monitoring (TDM) is recommended.
Aminoglycosides: Mechanism of Action
- Cross bacterial cell walls via porin channels; active transport across cell membranes (oxygen-dependent).
- Bind to 30S ribosomal subunit, causing misreading of genetic code.
- Leads to incorporation of incorrect amino acids and non-functional/toxic proteins, impacting bacterial metabolism.
- Bactericidal, concentration-dependent (Cmax 8-10 times > MIC).
- Post-antibiotic effect (PAE) lengthens with higher doses; allows extended interval dosing (single large dose).
Aminoglycosides: Antibiotic Resistance
- Production of inactivating enzymes.
- Decreased uptake (porin mutations, impaired oxygen-dependent transport).
- Increased efflux.
- Alterations in the 30S ribosomal subunit receptor protein.
Aminoglycosides: Antibacterial Spectrum
- Effective against most aerobic gram-negative bacilli, including multidrug-resistant strains ( Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter sp.).
- Synergistic effects with β-lactam antibiotics (e.g., treating Enterococcus faecalis and Enterococcus faecium endocarditis).
Aminoglycosides: Adverse Effects
- Ototoxicity and nephrotoxicity (risk increases with treatment duration > 5 days, high doses, age, renal insufficiency).
- Concurrent use with ototoxic (cisplatin, loop diuretics) or nephrotoxic drugs (vancomycin, amphotericin) should be avoided.
- Vertigo (especially with streptomycin).
- Neuromuscular paralysis (high doses, short infusion periods, concurrent neuromuscular blockers).
Aminoglycosides: Pharmacokinetics
- Poor absorption; parenteral administration (except neomycin).
- 30-60 minute infusions
- Hydrophilicity limits tissue concentrations; subtherapeutic levels possible.
- Inadequate CSF concentrations (intrathecal administration may be used); crosses placental barrier, accumulating in fetal plasma and amniotic fluid (risk of fetal deafness).
- 90% excreted unchanged in urine (TDM needed for renal impairment
Streptomycin
- Resistance develops readily; mainly second-line agent for tuberculosis (combination therapy needed).
- Used with tetracycline (plague, tularemia, brucellosis) or penicillin (enterococcal/viridans streptococcal endocarditis); gentamicin often preferred.
- Ototoxicity, nephrotoxicity, fetal auditory toxicity, neuromuscular paralysis.
Gentamicin
- Isolated from Micromonospora purpurea.
- Active against gram-positive and gram-negative bacteria; synergistic with β-lactams against resistant organisms (Pseudomonas, Proteus, Enterobacter, Klebsiella, Serratia, Stenotrophomonas).
- Not recommended as monotherapy for staphylococcal infections (rapid resistance).
- TDM advised.
- Topical use (burns, wounds, IV catheter prophylaxis).
- Intrathecal administration for gram-negative meningitis.
Gentamicin: Adverse Effects
- Nephrotoxicity (reversible, mild, occurs in 5–25% of patients after 3–5 days); TDM needed.
- Ototoxicity (potentially irreversible, may cause deafness).
Amikacin
- Effective against many gram-negative enteric bacteria resistant to gentamicin and tobramycin inactivation enzymes.
- Used for severe, hospital-acquired infections with multidrug-resistant gram-negative bacteria (Pseudomonas aeruginosa, Acinetobacter, Enterobacter).
- Liposomal amikacin (inhalation) under development for respiratory diseases.
Tobramycin
- Similar antibacterial spectrum and pharmacokinetics to gentamicin.
- Narrow spectrum; active against gram-negative bacteria (except S. aureus).
- Used for Pseudomonas aeruginosa in cystic fibrosis (good lung penetration; lower nephrotoxicity/ototoxicity risk via inhalation).
- Indicated for life-threatening gram-negative infections (neonatal meningitis, brucellosis, pelvic inflammatory disease, plague).
Neomycin & Kanamycin
- Closely related; active against gram-positive and gram-negative bacteria, some mycobacteria.
- Pseudomonas and streptococci often resistant.
- Topical/oral use only (too toxic for parenteral administration).
- Topical: infected skin lesions.
- Oral: bowel surgery preparation, hepatic coma.
Netilmicin
- Similar to gentamicin and tobramycin; used for serious infections resistant to gentamicin.
- Dosage and administration routes are the same as gentamicin.
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