大环内酯类药物
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❖ Second generation More active on G- organisms
Mechanism of action
❖ Target 50s ribosomal RNA
❖ Mechanism inhibition of translocation of mRNA
Mechanism of resistance
Polypeptide antibiotics
❖ Vancomycin & Teicoplanin ❖ Polymyxins ❖ bactitracin
Vancomycin
❖ Mechanism of action
Inhibit cell wall synthesis
❖ Antimicrobial spectrum:
Others: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc.
Erythromycin
❖Clinical uses
❖ As penicillin substitute in penicillin-allergic or resistant patients with infections caused by staphylococci, streptococci and pneumococci
❖ Distribution ❖ Metabolism:
Erythromycin&clarithromycin: in liver
❖ Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
Βιβλιοθήκη Baidu
Commomly used macrolides
Macrolides
❖ First generation ： 1950’s—erythromycin ❖ Second generation：1970’s—claithromycin
azithromycin ❖ Third generation：
Common properties of Macrolides
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
❖ Toxicity: nephrotoxicity & neurotoxicity
Baciteracin
❖ Active against gram-positive bacteria ❖ Inhibit cell wall formation ❖ No cross-resistance with other agents ❖ Topical use only because of nephrotoxicity
Lincomycin and Clindamycin
❖ Antimicrobial activity Gram-positive organisms Bacteroide fragilis and other anaerobes
❖ Mechanism Binding to 50s ribosome subunit and inhibiting protein synthesis
❖ Pertussis，diphtheriae ❖ Legionella and mycoplasma pneumonia ❖ H.p infection
Erythromycin
❖Adverse reactions
Gastrointestinal effects Liver toxicity Cardiotoxicity
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）
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
❖ Adverse reaction
Ototoxicity & nephrotoxicity Red-man syndrome
Teicoplanin
❖ Similar to vancomycin in mechanism and antimicrobial spectrum
❖ Can be given im as well as iv ❖ Less adverse reactions
Vancomycin
❖ Clinical uses
Infection caused by MRSA, MRSE and penicillinresistant pneumococcus
Treatment of antibiotic-associated enterocolitis caused by clostridium difficile po
❖ Adverse reactions Gastrointestinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole Other :Impaired liver function , neutropenia
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
Narrow spectrum, active only against grampositive bacteria paticularly staphylococci
❖ Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
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
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
Roxithromycin （罗红霉素，严迪）
❖ 1987 France ❖ The highest blood concentration ❖ F 72%~85% ❖ Respiratory tract infection and soft tissue
infection ❖ Low adverse effects
Chapter 38 Macrolides, Lincomycins
and Polymycins
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
❖ Pharmacokinetics Absorbed well Penetrate well into most tissues including bone
Clindaycin
❖ Clinical uses Severe anaerobic infection Acute or chronical suppurative osteomylitis , arthritis caused by susceptive organisms especially Staphylococci aureus
❖ Production of inactivating enzymes ❖ Modification of the ribosomal binding site ❖ Active efflux system ❖ MLSR
Pharmokinetics
❖ Absorption
Erythromycin: not stable at acid pH New macrolides: stable po
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.
Mechanism of action
❖ Target 50s ribosomal RNA
❖ Mechanism inhibition of translocation of mRNA
Mechanism of resistance
Polypeptide antibiotics
❖ Vancomycin & Teicoplanin ❖ Polymyxins ❖ bactitracin
Vancomycin
❖ Mechanism of action
Inhibit cell wall synthesis
❖ Antimicrobial spectrum:
Others: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc.
Erythromycin
❖Clinical uses
❖ As penicillin substitute in penicillin-allergic or resistant patients with infections caused by staphylococci, streptococci and pneumococci
❖ Distribution ❖ Metabolism:
Erythromycin&clarithromycin: in liver
❖ Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
Βιβλιοθήκη Baidu
Commomly used macrolides
Macrolides
❖ First generation ： 1950’s—erythromycin ❖ Second generation：1970’s—claithromycin
azithromycin ❖ Third generation：
Common properties of Macrolides
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
❖ Toxicity: nephrotoxicity & neurotoxicity
Baciteracin
❖ Active against gram-positive bacteria ❖ Inhibit cell wall formation ❖ No cross-resistance with other agents ❖ Topical use only because of nephrotoxicity
Lincomycin and Clindamycin
❖ Antimicrobial activity Gram-positive organisms Bacteroide fragilis and other anaerobes
❖ Mechanism Binding to 50s ribosome subunit and inhibiting protein synthesis
❖ Pertussis，diphtheriae ❖ Legionella and mycoplasma pneumonia ❖ H.p infection
Erythromycin
❖Adverse reactions
Gastrointestinal effects Liver toxicity Cardiotoxicity
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）
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
❖ Adverse reaction
Ototoxicity & nephrotoxicity Red-man syndrome
Teicoplanin
❖ Similar to vancomycin in mechanism and antimicrobial spectrum
❖ Can be given im as well as iv ❖ Less adverse reactions
Vancomycin
❖ Clinical uses
Infection caused by MRSA, MRSE and penicillinresistant pneumococcus
Treatment of antibiotic-associated enterocolitis caused by clostridium difficile po
❖ Adverse reactions Gastrointestinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole Other :Impaired liver function , neutropenia
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
Narrow spectrum, active only against grampositive bacteria paticularly staphylococci
❖ Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
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
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
Roxithromycin （罗红霉素，严迪）
❖ 1987 France ❖ The highest blood concentration ❖ F 72%~85% ❖ Respiratory tract infection and soft tissue
infection ❖ Low adverse effects
Chapter 38 Macrolides, Lincomycins
and Polymycins
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
❖ Pharmacokinetics Absorbed well Penetrate well into most tissues including bone
Clindaycin
❖ Clinical uses Severe anaerobic infection Acute or chronical suppurative osteomylitis , arthritis caused by susceptive organisms especially Staphylococci aureus
❖ Production of inactivating enzymes ❖ Modification of the ribosomal binding site ❖ Active efflux system ❖ MLSR
Pharmokinetics
❖ Absorption
Erythromycin: not stable at acid pH New macrolides: stable po
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.