Veterinary medicine, macrolides

Antimicrobial agents as well as macrolide antibiotics and fluoroquinolones used in human and veterinary medicine are of particular interest due to their potential for... 

ERAVMIS Environmental Risk Assessment of Veterinary Medicines in Slurry, 1999-2003), whose aim was to evaluate the impact of some veterinary antibiotics (mainly macrolides and sulphonamides)... 

Tilmicosin is a macrolide antibiotic exclusively used in veterinary medicine and resembling tylosin. It is approved for treatment of respiratory diseases in beef cattle and sheep by the subcutaneous route (100, 101). It is also indicated for treatment and control of respiratory diseases associated with mycoplasma in broiler chickens, but not in laying hens. Of major significance is that in contrast to other macrolides, tilmicosin is not safe for use in swine since fatalities may occur at dosage as low as 20 mg/kg bw (7). 

The importance of fermentation-derived antibiotics in veterinary medicine continues to increase. The following two classes of antibiotics, the macrolides and glycosides, were all obtained as metabolites of various Streptomyces species. 

The avermectins (Figure 3.67) have no antibacterial activity, but possess anthelmintic, insecticidal, and acaricidal properties, and these are exploited in human and veterinary medicine. The avermectins are also 16-membered macrolides, but their structures are made up from a much longer... 

This class of macrolide antibiotic has mostly antiparasitic activity. Avermectin Bia (45) and ivermectin (46) (O Scheme 18) are used mostly in veterinary medicine, however, some semisynthetic derivatives are also used for treatment of onchocerciasis in humans [59]. The action of avermectin is believed to stimulate specific chloride ion transport systems increasing the membrane permeability to Cl ions via GABA (y-butyrate) receptors and non-GABA receptors [60]. 

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Tylosin 33 from Streptomyces fradiae is a representative member of the large family of 16-membered macrolide antibiotics commonly utilised in veterinary medicine. The aglycone core, tylactone 34 is constructed from two acetate, five propionate and one butyrate units [68, 69]. The processive mechanism for its biosynthesis was demonstrated by the pioneering contributions of Hutchinson... 

The 16-membered macrolide antibiotics are generally classified into two large groups, namely, the leucomycin-related family and the tylosin-related family, on the basis of the substitution patterns of their aglycons (Fig. 28) [187]. Interestingly, the leucomycin series, such as leucomycin, josamycin, midecamycin, and spiramycin, have been used clinically for humans, while the tylosin series has been utilized in veterinary medicine. In this section, we describe recent studies on the chemical modification of 16-membered macrolides and their structure-activity relationships. 

Some of the macrolides used in veterinary medicine have been detected at trace levels in the environment. 

Giguere S, Macrolides, azalides and ketolides, in Giguere S, Prescott JE, Baggot JD, Walker RD, Dowling PM, eds.. Antimicrobial Therapy in Veterinary Medicine, 4th ed., Blackwell, Ames, lA, 2006, pp. 191-205. 

The macrolide antibiotics comprise an important and well-established class of antimicrobial agents. Several members from this large class have achieved prominent positions in either clinical or veterinary medicine. An excellent book covering many aspects of the macrolides before 1984 has been published [1]. In addition, several recent reviews have disQussed current usage of these antimicrobial agents [2, 3, 4, 5, 6]. 

This review will summarize structural modifications of the classical macrolide antibiotics which have been reported in the scientific literature during the past several years and will highlight those compounds which have exhibited potential utility in clinical or veterinary medicine. 

Reductive amination of the aldehyde group to aminomethyl derivatives has provided another route to potentially useful compounds. An initial report described the synthesis of primary amino derivatives of tylosin and leucomycin along with dimeric structures of each [140]. A group of derivatives of tylosin and demycarosyltylosin (desmycosin) were subsequently synthesized and shown to retain antimicrobial activity [141]. From a more extensive series of compounds prepared by reductive amination of tylosin and related macrolides, 20-deoxo-20-(3,5-dimethylpiperidinyl)desmycosin was selected for further development in veterinary medicine [142]. This compound, under the generic name of tilmicosin (see Fig. 7), is being evaluated for treatment of pneumonia in cattle and pigs [143, 144, 145]. 

The macrolide antibiotics are a group of compounds which have as a nucleus a ma-crocyclic lactone ring to which one or more sugars are attached. These sugars are essential for the antibiotic activity. Only three of the macrolides, i.e., erythromycin, oleandomycin, and spiramycin are used in human clinical practice, while a fourth, tylosin, is used in veterinary medicine and as a food preservative in industrial canning. These are all weakly alkaline and only slightly soluble in water. Erythromycin is the most active antibiotic of this group (Fig. 7). All of them are able to inhibit bacterial protein synthesis and are characterized by their bacteriostatic qualities. The antibacterial spectrum is similar to that of benzylpenicillin. 

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). 

Tylosin is a macrolid antibiotic used in veterinary medicine. Occupational exposure concerns farmers, breeders, animal-feed workers and veterinarians. 

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