Macrolide antibiotics resistance

Antibiotic resistance plays a smaller role in pharyngitis therapy compared with other URIs. O Penicillin resistance has not yet been documented in group A streptococci, but resistance and clinical failures occur more frequently with tetracyclines, trimethoprim-sulfamethoxazole, and to a lesser degree macrolides. 

Another example of solid phase DOS involves post-modification of the natural product macrolide antibiotic erythromycin (34) [77]. Erythromycin was first converted to analogue 32 which resembles a third generation macrolide antibiotic with high activity against resistant strains (ABT-773, 35), but is attached to solid phase-bound amino acids by reductive amination. Two further reductive amination steps and cleavage from solid support form a library of compounds of type 33 (Fig. 10). 

Macrolide antibiotics target the bacterial ribosome and inhibit the bacterial protein biosynthesis. Many gram-negative bacteria are inherently resistant to mac-rolides because their outer membrane is impermeable to macrolides. Several mechanisms of acquired resistance have been reported. In some cases, resistance is conferred by methylation of ribosomes by methylase enzymes, the genes of... 

Erythromycin is a macrolide antibiotic produced by Streptomyces erythreus. It is considered the most active macrolide for treatment of staphylococcal infections in cases of penicillin resistance. It is used parenterally at a dosage of 3-5 mg/kg bw, in intramammary form at 300 mg/quarter, and orally at 20-50 mg/kg bw. For treatment of mycoplasmal infections in poultry, an oral medication... 

Macrolides - [ANTIBIOTICS-MACROLIDES] (Vol3) - [ANTIBIOTICS - SURVEY] (Vol 2) -lmcosamimde co-resistances [ANTIBIOTICS - LINCOSAMINIDES] (Vol3)... 

Poehlsgaard J, Douthwaite S. Macrolide antibiotic interaction and resistance on the bacterial ribosome. Curr Opin Investig Drugs. 2003 4 140-148. 

Jenkins G, Cundliffe E (1991) Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene 108 55-62... 

Currently, one structure of a Irncosamide antibiotic bound to the ribosome is available for analysis [4]. like the macrolide antibiotics, drndamycin binds near the hydrophobic crevice at the entrance to the peptide exit turmel. As with the macrolide carbomycin A, dindamycin interacts not only with the hydrophobic crevice at the entrance to the peptide exit turmd, but also with the active site hydrophobic crevice. The nudeotides that surroimd the clindamydn binding site were previously implicated in binding of lincosamides based on nucleotide protection studies and on the analysis of mutations conferred by resistance (Fig. 4.4). 

Tu D, Blaha G, Moore PB, Steitz TA. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 2005 121 257-270. Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol. Cell 2002 10 117-128. 

Matsuoka M, Endou K, Kobayashi H, Inoue M, Nakajima Y. A plasmid that encodes three genes for resistance to macrolide antibiotics in Staphylococcus aureus. FEMS Microbiol. Lett. 1998 167 221-227. 

Seppala, H. Klankka, T. Vuopio-Vakila, J. Muotiala, A. Helenius, H. Lager, K. Huovinen, P. The effect of changes in consumption macrolide antibiotics on erythromycin resistance in Findland. N. Engl. J. Med. 1997, 337, 441-446. 

---