Untitled Quiz

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.