1. Background introduction
Macrolides are products of actinomycetes (soil bacteria) or semi-synthetic derivatives of them. Erythromycin is an orally effective antibiotic discovered in 1952 in the metabolic products of a strain of Streptocyces erythreus, originally obtained from a soil sample.
A macrolide is actually a complex mixture of closely related antibiotics that differ from one another with respect to the chemical substitutions on the various carbon atoms in the structure and in the aminosugars and neutral sugars. For example, erythromycin is mostly erythromycin A, but B, C, D, and E forms may also be included in the preparation.
The macrolide antibiotics are colorless, crystalline substances. They contain a dimethylamino group, which makes them basic. Although they are poorly water soluble, they do dissolve in more polar organic solvents. Macrolides are often inactivated in basic (pH larger than 10) as well as acidic environments (pH less than 4 for erythromycin). The multiple functional groups make it possible for them to undergo a large number of chemical reactions. More stable ester forms, eg, acetylates, estolates, lactobionate, succinates, propionates, and stearates, are commonly used in pharmaceutical preparations.
2. Therapeutic indications
The macrolides are used to treat both systemic and local infections. They are often regarded as alternatives to penicillins for treatment of streptococcal and staphylococcal infections. General indications include upper respiratory tract infections, bronchopneumonia, bacterial enteritis, metritis, pyodermatitis, urinary tract infections, arthritis, and others. Macrolides are indicated for treatment of Rhodococcus respiratory tract infections in foals. Formulations to treat mastitis are also available and often have the advantage of a short withholding time for milk. Tilmicosin, gamithromycin, and tulathromycin are approved for use in treatment of bovine respiratory diseases associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. In swine, tilmicosin phosphate is added to feed or water for control of swine respiratory disease.
3. Mechanism of action and resistance
3.1 Mode of action
The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere with protein synthesis by reversibly binding to the 50S subunit of the ribosome. They appear to bind at the donor site, thus preventing the translocation necessary to keep the peptide chain growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas. Macrolides are regarded as being bacteriostatic but demonstrate bactericidal activity at high concentrations. Macrolides are significantly more active at higher pH ranges (7.8–8). Macrolides are considered to be time dependent in terms of antimicrobial efficacy.
3.2 Bacterial resistance
Methylation of the 50S ribosome (altered target affinity)
Altered cell wall permeability (reduced expression of porins, or expression of porins with modified selectivity)
4. Adverse effects and toxicity
Toxicity and adverse effects are uncommon for most macrolides (except tilmicosin), although pain and swelling may develop at injection sites. Hypersensitivity reactions have occasionally been seen. Erythromycin estolate may be hepatotoxic and cause cholestasis; it may also induce vomiting and diarrhea, particularly when high doses are administered. Horses are sensitive to macrolide-induced GI disturbances that can be serious and even fatal. In pigs, tylosin may cause edema of the rectal mucosa, mild anal protrusion with diarrhea, and anal erythema and pruritus. After 5 mg/kg/day, dogs had a greater tendency to develop ventricular tachycardia and fibrillation during acute myocardial ischemia. Tilmicosin is characterized by cardiac toxicity (tachycardia and decreased contractility). Parenteral (but not oral) administration should be avoided in swine, and extra-label use should be avoided. Cattle have died after IV injection of tilmicosin, and human injury is possible after accidental exposure.
5. Introduction of our products
100013 - Tylosin Rapid Test Kit
100017 - TriTest BTM Rapid Test Kit
100020 - TriTest LQT Rapid Test Kit
100023 - Macrolides Rapid Test Kit
100024 - QuaTest QMLE Rapid Test Kit
