1. Macrolides, Lincomycins
Chapter 38
Macrolides, Lincomycins
and Polymycins

2. 大环内酯类药物 14元大环内酯类：红霉素、罗红霉素、克拉霉素、地红霉素 15元大环内酯类：阿奇霉素
16元大环内酯类：螺旋霉素、乙酰螺旋霉素、麦迪霉素、麦白霉素、罗他霉素、柱晶白霉素、交沙霉素、米欧卡霉素

3. Macrolides First generation ： 1950’s—erythromycin
Second generation：1970’s—claithromycin azithromycin
Third generation：

4. Common properties of Macrolides

5. Antibacterial activity
First generation
Most G+ organisms: pneumococci, streptococci, staphylococci , diphtheriae etc
Part G- organisms:legionella（军团菌）,bacillus pertussis(百日咳), brucella(布氏) etc
Others: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc.
Second generation
More active on G- organisms

6. Mechanism of action Target 50s ribosomal RNA Mechanism
inhibition of translocation of mRNA

9. Mechanism of resistance
Production of inactivating enzymes
Modification of the ribosomal binding site
Active efflux system
MLSR

10. Pharmokinetics Absorption Distribution Metabolism: Excretion
Erythromycin: not stable at acid pH
New macrolides: stable po
Distribution
Metabolism:
Erythromycin&clarithromycin: in liver
Excretion
Erythromycin& azithromycin: bile
Clarithromycin: kidney

11. Commomly used macrolides

12. Erythromycin Antimicrobial activity
Gram-positive organisms: pneumococci, streptococci, staphylococci , diphtheriae etc
Gram-negative organisms:legionella（军团菌）,bacillus pertussis(百日咳), brucella(布氏) ,
meningococci, diplococcus gonorrhoeae etc
Others: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc.

13. Erythromycin Clinical uses
As penicillin substitute in penicillin-allergic or resistant patients with infections caused by staphylococci, streptococci and pneumococci
Pertussis，diphtheriae
Legionella and mycoplasma pneumonia
H.p infection

14. Erythromycin Adverse reactions Gastrointestinal effects Liver toxicity
Cardiotoxicity

15. Erythromycin Erythromycin lactobionate(乳糖酸红霉素）
erythromycin estolate（无味红霉素)
erythromycin stearate(硬脂酸红霉素）
erythromycin ethylsuccinate（琥乙红霉素，
利君沙）

16. New macrolides antibiotics
Advantage :
Broader spectrum, higher activity
Orally effective
High blood concentration
Longer t 1/2
Less toxicity
Mainly used in respiratory tract infection

17. Clarithromycin（甲红霉素,克拉霉素）
Has the strongest activity on Gram-positive bacteria, legionella pneumophila, chlamydia pneumoniae and H.p
Good pharmacokinetic property
Low toxicity

18. Azithromycin (阿齐霉素,丽珠奇乐）
Has the strongest activity against mycoplasma pneumoniae（肺炎支原体）
More effective on Gram-negative bacteria
Well tolerated
T1/2 :35~48h once daily
Mainly used in respitory tract infection

19. Roxithromycin （罗红霉素，严迪）
France
The highest blood concentration
F 72%~85%
Respiratory tract infection and soft tissue infection
Low adverse effects

20. Lincomycin and Clindamycin
Antimicrobial activity
Gram-positive organisms
Bacteroide fragilis and other anaerobes
Mechanism
Binding to 50s ribosome subunit and inhibiting protein synthesis
Pharmacokinetics
Absorbed well
Penetrate well into most tissues including bone

21. Clindaycin Clinical uses Severe anaerobic infection
Acute or chronical suppurative osteomylitis , arthritis caused by susceptive organisms especially Staphylococci aureus
Adverse reactions
Gastrointestinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole
Other :Impaired liver function , neutropenia

22. Polypeptide antibiotics
Vancomycin & Teicoplanin
Polymyxins
bactitracin

23. Vancomycin Mechanism of action Antimicrobial spectrum:
Inhibit cell wall synthesis
Antimicrobial spectrum:
Narrow spectrum, active only against gram-positive bacteria paticularly staphylococci
Pharmacokinetics
Poorly absorbed from intestinal tract, iv
Excreted from glomerular filtration 90%

24. Vancomycin Clinical uses Adverse reaction
Infection caused by MRSA, MRSE and penicillin-resistant pneumococcus
Treatment of antibiotic-associated enterocolitis caused by clostridium difficile po
Adverse reaction
Ototoxicity & nephrotoxicity
Red-man syndrome

25. Teicoplanin
Similar to vancomycin in mechanism and antimicrobial spectrum
Can be given im as well as iv
Less adverse reactions

26. Polymyxins
Active only against gram-negative rods, particularly P.aeruginosa
Mechanism:increase permeability of cell membrane
Mainly used in P.aeruginosa infection when other drugs are resistant
Toxicity: nephrotoxicity & neurotoxicity

27. Baciteracin Active against gram-positive bacteria
Inhibit cell wall formation
No cross-resistance with other agents
Topical use only because of nephrotoxicity