
Full text loading...
Category: Bacterial Pathogenesis
Macrolides, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815929/9781555812379_Chap18-1.gif /docserver/preview/fulltext/10.1128/9781555815929/9781555812379_Chap18-2.gifAbstract:
The natural macrolides of importance in human pathology are the 14- and 16-membered-ring macrolides; the semisynthetic derivatives of importance in human pathology are the 15-membered-ring macrolides (azalides). A characteristic of new molecules is the increased acid stability of the macrolides. This can be fully achieved with roxithromycin and azithromycin. The principal physicochemical properties of the macrolides are listed in this chapter. The natural antibacterial spectrum of the macrolides, irrespective of their structure, includes gram-positive bacteria; gram-negative cocci; fastidious gram-negative bacilli, such as Haemophilus influenzae, Moraxella catarrhalis, Pasteurella spp., and Bordetella spp.; anaerobic bacteria; intracellular bacteria; mycoplasmas and related species; spirochetes; bacteria responsible for gastrointestinal infections (V. cholerae and other Vibrio spp. and Campylobacter spp.); and H. pylori. Roxithromycin and azithromycin are very effective in experimental infection in rabbits with Treponema pallidum strain Nichols, whereas these molecules have cross-resistance with erythromycin A, as has been demonstrated with an erythromycin A-resistant strain of T. pallidum. The macrolides inhibit protein synthesis by binding to the 50S subunit of the bacterial ribosomes. The absorption and bioavailability of macrolides vary according to the molecule, partly explaining the difference in unit and dosage rhythm of the different macrolides. Many publications have shown that macrolides have nonantibiotic pharmacological effects. Some of these effects have been studied for their therapeutic potential (motilide) or are the subject of important basic research: anti-inflammatory or cardiological effects.
Full text loading...
Erythromycin A
Classification of macrolides
Erythromycin A 2′-esters
Oleandomycin
Modification of the substituent at position 8
Sites of modification of erythromycin A
Flurithromycin
Dirithromycin
Roxithromycin
Chemical modifications of 9-N-oxime erythromycin A
8a- and 9a-azalides
Azithromycin
8a-Aza-8a-homeoerythromycin
14-Membered-ring azalides
Degradation of erythromycin A in an acidic medium
Spiramycins
Stability of roxithromycin at pH 4.2
Clarithromycin
Pseudoclarithromycin
Azithromycin: degradation in an acidic medium
16-Membered-ring macrolides
Electronic interactions of erythromycin A
Inhibition of 50S ribosomal subunit biosynthesis
S. pneumoniae : resistance to erythromycin A in Asia
S. pneumoniae : resistance to erythromycin A in Europe (1999 to 2000)
H. pylori : resistance to erythromycin A in Europe (1999)
The ermC gene: schematic representation of the conformational rearrangement following inhibition by erythromycin A
Mode of action of esterases on the erythronolide A ring
Structure of miokamycin and its principal metabolites
Inactivation of erythromycin A
Inactivation of oleandomycin
Bottle brush mechanism of resistance
Metabolism of clarithromycin
Structure of miokamycin and its principal metabolites
Metabolism of miokamycin (from Shomura et al., 1981)
Metabolism of rokitamycin
Cytochrome P450 interactions
Prokinetic agents
Discoveries of macrolides
Plasma pharmacokinetics of erythromycin A
Plasma pharmacokinetics of erythromycin A stearate (250 mg orally)
Hydrolysis half-life of the 2′-esters of erythromycin A (37°C)
In vitro activities of azalides against E. coli
In vitro activities of the 14-membered azalides
Physicochemical properties of macrolides
Classification of macrolides according to their intracellular properties
Accumulation ratios (cellular/extracellular) of the main macrolides (in vitro) a
In vitro activities of natural macrolides against common pathogens
In vitro activities of group IIA and group IIB macrolides against gram-positive cocci
In vitro activities of group IIA and group IIB macrolides against gram-positive bacilli
In vitro activities of group IIA and IIB macrolides against gram-negative bacilli
In vitro activities of macrolides against H. pylori as a function of pH of the culture medium
Resistance of H. pylori to clarithromycin
In vitro activities of macrolides against C. jejuni
Activities of macrolides against anaerobic bacteria a
In vitro activities of macrolides against intracellular and atypical bacteria
Activities of macrolides against C. psittaci LOTH a
Activities of macrolides against Rickettsia spp. a
Activities of macrolides against Bartonella spp. a
In vitro activities of antibiotics against
In vitro activities of 16-membered-ring macrolides
In vitro activities of 16-membered-ring macrolides a
Breakpoints of macrolides of the French Antibiotic Sensitivity Test Committee (1997)
Breakpoints of erythromycin A (15-μg disks)
NCCLS breakpoints for S. pneumoniae (1997) a
NCCLS breakpoints for staphylococci (1997)
Resistance of Lancefield group A streptococci to erythromycin A
Epidemiology of resistance among gram-positive cocci in the United States
erm genes and bacteria
Resistance of M. pneumoniae to erythromycin A a
Inactivation of macrolides by MPH-2′ a
Activities of 14-membered-ring macrolides against streptococci resistant to erythromycin A by efflux a
Activities of antibiotics of the MLS group against different strains of S. aureus a
Combination of mechanisms of resistance to erythromycin A in S. pneumoniae a
Plasma pharmacokinetics of macrolides
Urinary elimination of macrolides
Pharmacokinetics of erythromycin A ethyl succinate a
Pharmacokinetics of erythromycin A estolate a
Residual concentrations of azithromycin in plasma after repeated doses a
Pharmacokinetics of macrolides administered intravenously
Clarithromycin concentrations in plasma at the end of infusion of increasing doses
Absolute bioavailability of macrolides
Macrolides: repeated dose pharmacokinetics
Macrolide pharmacokinetics after food
Pharmacokinetics of erythromycin A stearate in elderly patients after repeated doses
Pharmacokinetics of spiramycin in elderly subjects after repeated intravenous doses of 500 mg every 8 h for 6 days
Pharmacokinetics of macrolides in elderly patients
Pharmacokinetics of dirithromycin in elderly patients (dose of 500 mg once a day)
Pharmacokinetics of roxithromycin in elderly subjects
Pharmacokinetics of erythromycin in children
Pharmacokinetics of roxithromycin in children
Pharmacokinetics of 16-membered-ring macrolides in children
Pharmacokinetics of clarithromycin in children
Pharmacokinetics of clarithromycin in low-body-weight neonates
Concentrations of clarithromycin in plasma and middle ear fluid
Pharmacokinetics of clarithromycin in middle ear fluid
Repeated-dose pharmacokinetics of azithromycin in children
Distribution of macrolides in the middle ear fluid (or effusion)
Macrolide and ketolide concentrations in tonsils a
Concentrations of macrolides and ketolides in saliva
Protein binding of macrolides
Pharmacokinetics of azithromycin in patients with hepatic insufficiency
Pharmacokinetics of roxithromycin in patients with hepatic insufficiency
Pharmacokinetics of dirithromycin in patients with hepatic insufficiency
Pharmacokinetics of miokamycin in cirrhotic patients
Rectal pharmacokinetics of erythromycin base
Gastrointestinal bioavailability of azithromycin
In vitro activities of clarithromycin metabolites
Distribution of azithromycin products after repeated oral administration (total of 1.5 g over 5 days)
Metabolites of azithromycin
Tissue distribution of macrolides
Nonexhaustive list of drugs whose metabolism may interfere with that of macrolides
Pharmacokinetics of the combination of midazolam and erythromycin base
Bioavailability of terfenadine in combination with macrolides
Drug interference by macrolides
In vitro activity of macrolides against T. gondii (MRC5 fibroblasts) a
Preventive activity of roxithromycin in ischemic events in patients suffering from unstable angina