Wednesday, November 14, 2007

Antibiotics - macrolides, ketolids, streptogramins, clindamycin


  • Have similar activity
  • Major differences in side effects, half lives (frequency of dosage), admin method
  • Obtained from streptomyces erythreus
  • Binds to 50s ribosomal DNA - bacteriostatic/cidal depending on dosage and susceptibility
- Activity

  • G+ve stuff - pneumococci, strep, staph, corynebacterium
  • atypicals - chlamydia, mycoplasma, legionella, helicobacter, listeria
  • mycobacteria
- Resistance

  • Plasmid encoded
  • Cross-resistance complete btw all macrolides
- Clinical uses + SE

  • Stimulates gut motility - used in post operative gut surgery to promote gastric emptying - only for erythromycin NOT other macrolides
  • Due to this SE - we don't use them a lot routinely
  • Liver toxic
  • Inhibit cP450

  • increased activity with g+ve (Horvath)
  • advantage over erythromycin - lower GIT SE, better gut absorption - hence used in eradication of H. pylori

  • Difference from above - penetrates tissue extremely well - [tissue] > [serum] - hence slowly released from tissue = longer T1/2 of 3 days
  • hence once daily dosing
  • 1g = 7 day of doxycycline

  • semisynthetic macrolide
  • 3-keto group added
  • eg: telithromycin
- no longer used due to toxicity
- like erythromycin in activity - binds 50s ribosomal subunit - reduce toxin production - hence used in necrotising fasciitis (reduces exotoxin produced by Strep)
- covers g+ve (strep, staph, pneumococci) and anaerobes
- doesn't cover: enterococci, g-ve aerobic, clostridium

- bacteriostatic --> hence if someone has staph bacteremia --> treat with fluclox first to kill, then use clindamycin orally --> if not use clindamycin + other agents eg rifampicin (never use this alone)
- has excellent oral bioavailability (one of those to use orally unless mechanical reason, like ciprofloxacin)

- clinical uses

  • has the best oral bioavailability for staph (1st clindamycin, 2nd fluclox, 3rd augmentin, last keflex)
  • severe anaerobic infection (bacteroides)
- SE

  • diarrhoea - major SE leading to disuse
  • colitis - usually pseudomembranous
- g+ve: staph, strep, enterococci, listeria, corynebacteria
- binds to 23S ribosomal RNA of 50S subunit - unique to linezolid - hence there's no cross resistance
- problem: hematologic toxic - low PLT most common (3%), neutropaenia
- use: VRE

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