Polymyxins, Macrolides and Lincosamides

• When were polymyxins discovered?

  In 1947
• What are the two types of polymyxins?

  Polymyxin B and polymyxin E (colistin)
• What is the molecular weight of polymyxins?

  1400
• What are the components of polymyxins?

  They are cationic detergents consisting of a fatty acid chain (lipophilic) and an amino acid group (lipophobic)
• How do polymyxins act on bacterial membranes?

  They act as detergents that disrupt the integrity of the bacterial outer membranes
• What happens to the bacterial cell membrane when polymyxins interact with it?

  The lipophilic portion interacts with the fatty acid part of the phospholipid, leading to cell leakage and cell death
• What type of effect do polymyxins have on bacteria?

  Bactericidal
• What determines the susceptibility of bacteria to polymyxins?

  The concentration of phospholipids in the bacterial cell
• Why are Gram-negative microbes more susceptible to polymyxins?

  They have a higher concentration of phospholipids, decreasing resistance and making therapy effective
• Why are Gram-positive microbes resistant to polymyxins?

  They have a lower concentration of phospholipids, higher resistance and intact cell membrane integrity
• How are polymyxins absorbed when given orally?

  They are poorly absorbed-> used to treat diarrhea
• Why are polymyxins not used parenterally?

  Due to acute nephrotoxicity
• When are polymyxins recommended to be administered intravenously?

  For ICU patients with very resistant Gram-negative bacterial infections
• Polymyxins poorly penetrate tissues, except where in the body?

  Except for the kidneys
• How are polymyxins excreted from the body?

  They are excreted renally and concentrate in renal tissues
• What is the antimicrobial spectrum of polymyxins?

  They are more effective against Gram-negative bacteria, especially coliform organisms and Pseudomonas spp.
• What is the primary clinical use of polymyxins?

  They are mainly used as topical medications for skin, eye, or ear infections
• Why is there an increased parenteral use of polymyxins being advocated today?

  Recent research findings suggest that the toxicity potential is overblown
• What type of nephrotoxicity is associated with polymyxins?

  Tubular necrosis
• What are the neurotoxic(rare) effects of polymyxins?

  They can cause neuromuscular blockade and respiratory paralysis (when used with muscle relaxants in surgery)
• What are the main macrolides mentioned?

  Erythromycin, clarithromycin, azithromycin, and telithromycin
• What is the antimicrobial spectrum of macrolides?

  They are effective against Gram-positive organisms and some Gram-negative cocci. (strep pyogens, pneumoni, mycoplasma pneumonia and legionella)
• How does the antimicrobial activity of macrolides vary?

  It can be bactericidal or bacteriostatic, depending on the concentration
• At what pH are macrolides more active?

  At alkaline pH
• What is the mechanism of action of macrolides?

  They bind to the 50S ribosomal subunit and inhibit peptide bond formation
• What is a common mechanism of resistance to macrolides?

  Modification of the ribosomal binding site
• What can hydrolyze macrolides?

  Production of esterase
• What is the effect of reduced permeability of the cell membrane on macrolides?

  It contributes to resistance against macrolides
• What is the relationship between erythromycin and other macrolides?

  There is complete cross-resistance between erythromycin and other macrolides
• How are stearate and ester forms of erythromycin characterized?

  They are fairly acid-resistant and somewhat better absorbed
• How does food affect the absorption of macrolides?

  Food interferes with absorption
• Do macrolides cross the blood-brain barrier?

  No, they do not cross the blood-brain barrier
• Where do erythromycin and its metabolites concentrate in the body?

  In the liver
• What is the spectrum of antibacterial activity of macrolides compared to penicillins?

  Macrolides are similar to penicillins regarding their spectrum of activity
• What are some adverse reactions associated with macrolides?

  GI effects, hepatotoxicity, cardiotoxic effects, ototoxicity, and hypersensitivity reactions
• What is a common GI effect of macrolides?

  Nausea, vomiting, and abdominal cramps
• What type of hepatitis can macrolides cause?

  Cholestatic hepatitis
• What is a potential effect of erythromycin on the heart?

  Cardiotoxic effects
• What is a rare adverse effect associated with erythromycin?

  Transient deafness with erythromycin at high doses
• What can inhibit cytochrome P450 enzyme?

  Erythromycin metabolites