Gram-positive/negative bacteria macrolides

O-phosphotransferases that modify macrolides are produced by highly macrolide resistant E. coli isolates. However, these enzymes have no clinical importance for macrolide resistance in gram-positive bacteria, and gram-negative ones are regarded as naturally resistant [2]. 

Antibacterial activity of macrolides depends on the acidity of the medium. High activity is observed in neutral and basic media in comparison with acid. In particular, erythromycin is inactivated in the acidic medium of the stomach. Macrolides have a relatively broad spectrum of use, and they are active with respect to Gram-positive and Gram-negative microorganisms, achiomycetes, mycoplasma, spirochaeta, chlamydia. Bacteria Rickettsia, certain mycobacteria. Colon bacillus, blue-pus bacillus, shigella, salmonella, and so on. 

Erythromycin and the other macrolides exhibit a very broad spectrum of antibacterial activities and are active against many gram-positive bacteria, as well as some gram-negative bacteria. These agents are often used as the primary or alternative drug in a variety of clinical conditions (see Table 33-5). Macrolides may be especially useful in patients who are allergic to penicillin. 

Macrolide antibiotics are bacteriostatic for gram-positive and -negative bacteria therefore, they inhibit bacteria reproduction but do not kill the bacteria. Bacteria are killed by the immune system. Macrolide antibiotics are prescribed for soft tissue, skin, respiratory, and gastrointestinal tract infections. 

Both antibiotic-specific and MDR pumps are known to confer clinically relevant resistance [22, 53]. The former are carried on plasmids and transposons. While they can be rapidly spread between various strains, they are at hand only in a proportion of a total population of a given species. Tet and Mef pumps, which confer resistance to tetracycline and macrolides, respectively, in both Gram-positive and Gram-negative bacteria, are clinically important and highly prevalent antibiotic-specific transporters. 

Tilmicosin, Figure 1, is a new semisynthetic antibiotic derived from the macrolide antibiotic tylosin. The synthesis and antibacterial activity of tilmicosin have been described by Debono, et al. and Kirst, et al. (/-4). Tilmicosin has in vitro activity against a variety of Gram positive and Gram negative bacteria, as well as mycoplasma species. It is effective for treatment of bovine respiratory disease caused by Pasteurella haemolytica when administered as a single subcutaneous injection (5, 6). This paper describes the excretion, tissue residue pattern, and metabolism of tilmicosin when injected into cattle, and also gives comparative metabolism data from rats which were dosed orally. 

Goldman, R. C., Fesik, S. W., and Doran, C. C. (1990). Role of protonated and neutral forms of macrolides in binding to ribosomes from gram-positive and gram-negative bacteria. Antimicrob. Agents Chemother. 34, 426-431. 

Fig. 1. Schematic structures of macrolide antibiotics and their antibiotic activities against bacteria representative of gram-positive S. aureus or gram-negative E. coli.

Although macrolides can bind to 238 ribosomal RNAs of both gram-positive and gram-negative bacteria, incorporation and accumulation of sufficient amounts of macrplide into the cells are necessary to exhibit bactericidal or bacteriostatic effect. 

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