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What is the primary mechanism of action for 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?
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?
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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?
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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?
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Which type of administration is NOT associated with gentamicin?
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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?
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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?
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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?
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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?
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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?
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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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