chapter 38 macrolides, lincomycins and polymycins
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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. Macrolides. First generation : 1950’s—erythromycin Second generation : 1970’s—claithromycin azithromycin - PowerPoint PPT PresentationTRANSCRIPT
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
Macrolides
First generation : 1950’s—erythromycin Second generation : 1970’s—claithromycin
azithromycin Third generation :
Common properties of Macrolides
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
Mechanism of action Target
50s ribosomal RNA Mechanism
inhibition of translocation of mRNA
Mechanism of resistance
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
Distribution Metabolism:
Erythromycin&clarithromycin: in liver Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
Commomly used macrolides
Erythromycin
Antimicrobial activity Gram-positive organisms: pneumococci, stre
ptococci, 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 trach
omatis( 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
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
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
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
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
Clindaycin
Clinical uses Severe anaerobic infection Acute or chronical suppurative osteomylitis , arthrit
is caused by susceptive organisms especially Staphylococci aureus
Adverse reactions Gastrointestinal effects: severe diarrhea and pseud
omembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole
Other :Impaired liver function , neutropenia
Polypeptide antibiotics
Vancomycin & TeicoplaninPolymyxinsbactitracin
Vancomycin
Mechanism of action Inhibit cell wall synthesis
Antimicrobial spectrum: Narrow spectrum, active only against gram-positi
ve bacteria paticularly staphylococci Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
Vancomycin
Clinical uses Infection caused by MRSA, MRSE and penicillin-
resistant pneumococcus Treatment of antibiotic-associated enterocolitis ca
used by clostridium difficile po 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
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
Baciteracin
Active against gram-positive bacteria Inhibit cell wall formation No cross-resistance with other agents Topical use only because of nephrotoxicity