Macrolide antibiotics antimicrobial activity

Several 16-membered macrolides form metabolites which retain antimicrobial activity. As discussed above, 3"-esters such as rokitamycin and miokamycin produce prolonged concentrations of antibiotic in vivo due to the facile 3"- to 4"-0-acyl migration that follows enzymatic removal of the original 4 -ester [34, 269, 270], Following a different approach to overcome the lability of 4"-esters, specific 4"-0-acyl derivatives of tylosin were selected from the series of esters (15) based upon their greater stability toward liver enzymes [80], Although esterases play the most prominent role in metabolism of 16-membered macrolides, other mechanisms such as oxidative hydroxylation, A-demethylation, reduction, and hydrolysis of sugars have been reported for various compounds [91, 96, 115, 259, 270-272]. 

Macrolide antibiotics are a homogeneous group of antimicrobial drugs that have been used to treat clinical infections for several decades. The most clinically useful classification of the macrolides is based on the size of the lactone ring that forms the chemical nucleus of each macrolide molecule [1, 2]. The 14- and 15-membered macrolides include erythromycin, clarithromycin, dirithromycin, roxithromycin, and azithromycin. Erythromycin is the oldest and still the most important of the macrolide antibiotics because it is a useful alternative to penicillin G. It is one of the safest antibiotics available. Clarithromycin and azithromycin have shown some advantages over erythromycin in their antibacterial activity,... 

Most of the data on rokitamycin have been published in Japanese and Italian journals. As a propionyl ester of leucomycin, rokitamycin has an antimicrobial spectrum similar to that of erythromycin, it is especially potent against L. pneumophila, M. pneumoniae, and Chlamydia. Like other 16-membered macrolides, it is active against bacteria that are inducibly resistant to erythromycin but inactive against strains that are constitutively resistant to macrolide-lincosamide-streptogramin B antibiotics. 

Research activity in the macrolide antibiotic class has been intense recently in attempts to reduce side effects and to broaden their antimicrobial spectra. The ketolides are a group of agents that are characterized by oxidation of the 3-position from an alcohol to a ketone. They are active against a significant number of erythromycin-resistant microorganisms. Recent investigation has been intense and a new agent has been introduced. 

The need for proper interpretation of the high tissue/serum ratios of macrolides and their clinical relevance have been recently reviewed [257-259]. Numerous studies have been published demonstrating intracellular uptake of macrolides. This phenomenon helps to explain their antimicrobial activity against many pathogens which reside in an intracellular environment, such as species of Legionella, Chlamydia, Salmonella, staphylococci, and mycobacteria. If the compound is bioavailable, high tissue concentrations of antibiotic would permit better eradication of infections localized within that tissue. 

Oleandoniycin. C35H ,NO,2, Mr 687.87, mp. 110°C, [a][> -65° (CH3OH). Internationa free name for a 14-membered macrolide antibiotic with a broad spectrum of antimicrobial activity isolated from cultures of Streptomyces antibioticus. O. is readily soluble in methanol, ethanol, butanol, acetone, less soluble in wa-... 

Oleandomycin, a 14-membered ring macrolide antibiotic, was isolated in 1956 from fermentation broths of Streptomyces antibioticus [360]. Some years later, oleandomycin was assigned the structure 340 on the basis of its chemical degradation [361]. Oleandomycin is effective, but less potently, against the same spectrum of bacteria as erythromycin, namely Gram-positive bacteria such as staphylococci, streptococci, and pneumococci. The antimicrobial activity of oleandomycin, when combined with tetracycline, is potentiated. In fact, in such a combination it is sold as an antibacterial agent for upper and lower respiratory tract infection. 

Prophylaxis of infections in HSCT patients is in many ways similar to that used in other neutropenic patients. Selective decontamination with oral antimicrobials is used commonly considerations are the same as those discussed previously. Although some studies have shown decreased rates of bacteremia and other bacterial infections after HSCT, overall mortality rates were not reduced. The routine use of prophylactic antibiotics in HSCT therefore is still controversial. Fluoroquinolones have become the most frequently used agents, often combined with another agent (e.g., macrolides or rifampin) for enhanced gram-positive activity. These regimens usually are begun... 

Direct skin contact of the veterinarian with animal medications has probably diminished since the 1970s in many countries. Antibiotics (and other medications) used in veterinary medicine and also animal feed are mainly the same as in human medicine, e.g., penicillins, cephalosporins, macrolides, tetracyclines, quinol-ones, sulfas, trimethoprim, antifungals. In addition, other substances have been used in animals only, e.g., penethamate, tylosin, spiramycin, furazolidone. Many antimicrobials are contact sensitizers and may cause contact dermatitis at low concentrations. No routine series for patch testing can be recommended because of the risk of active sensitization. Patch testing should be done with the particular medications with which the veterinarian has been in contact directly or via fodder. Contact urticaria from several antibiotics and disinfectants has also been reported (Hannuksela 1997b Kanerva 1997). 

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