大环内酯类药物
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Narrow spectrum, active only against grampositive bacteria paticularly staphylococci
Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
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
Distribution Metabolism:
Erythromycin&clarithromycin: in liver
Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
Commomly used macrolides
Macrolides
First generation ： 1950’s—erythromycin Second generation：1970’s—claithromycin
azithromycin Third generation：
Common properties of Macrolides
Second generation More active on G- organisms
Mechanism of action
Target 50s ribosomal RNA
Mechanism inhibition of translocation of mRNA
Mechanism of resistance
Pertussis，diphtheriae Legionella and mycoplasma pneumonia H.p infection
Erythromycin
Adverse reactions
Gastrointestinal effects Liver toxicity Cardiotoxicity
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
Adverse reactions Gastrointestinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole Other :Impaired liver function , neutropenia
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
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
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
Polypeptide antibiotics
Vancomycin & Teicoplanin Polymyxins bactitracin
Vancomycin
Mechanism of action
Inhibit cell wall synthesis
Antimicrobial spectrum:
Vancomycin
Clinical uses
Infection caused by MRSA, MRSE and penicillinresistant pneumococcus
Treatment of antibiotic-associated enterocolitis caused by clostridium difficile po
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
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
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
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.
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
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 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
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）
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
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
Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
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
Distribution Metabolism:
Erythromycin&clarithromycin: in liver
Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
Commomly used macrolides
Macrolides
First generation ： 1950’s—erythromycin Second generation：1970’s—claithromycin
azithromycin Third generation：
Common properties of Macrolides
Second generation More active on G- organisms
Mechanism of action
Target 50s ribosomal RNA
Mechanism inhibition of translocation of mRNA
Mechanism of resistance
Pertussis，diphtheriae Legionella and mycoplasma pneumonia H.p infection
Erythromycin
Adverse reactions
Gastrointestinal effects Liver toxicity Cardiotoxicity
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
Adverse reactions Gastrointestinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole Other :Impaired liver function , neutropenia
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
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
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
Polypeptide antibiotics
Vancomycin & Teicoplanin Polymyxins bactitracin
Vancomycin
Mechanism of action
Inhibit cell wall synthesis
Antimicrobial spectrum:
Vancomycin
Clinical uses
Infection caused by MRSA, MRSE and penicillinresistant pneumococcus
Treatment of antibiotic-associated enterocolitis caused by clostridium difficile po
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
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
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
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.
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
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 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
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）
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
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