Bacteria macrolide-resistant

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]. 

R Okamoto, H Nomura, M Tsuchiya, H Tsunekawa, T Fukumoto, T Inui, T Sawa, T Takeuchi, H Umezawa. The activity of 4"-<9-acylated tylosin derivatives against macrolide-resistant Gram-positive bacteria. J Antibiot 32 542-544, 1979. 

Moxifloxacin has a broad spectrum of activity which includes Gram-positive cocci, atypical pathogens and anaerobic bacteria responsible, inter alia, for infections of the respiratory tract. Moreover, moxifloxacin is one of the most effective fluoroquinolones against pneumococci, including the penicillin- and macrolide-resistant strains. The development of resistance to moxifloxacin is slower than that of the other fluoroquinolones. 

Another worrisome trend is the increased in vitro resistance reported for many gram-positive bacteria. Of greatest concern is the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA). Treatment choices for SSTIs have been further complicated by the increased incidence of macrolide-resistant strains of S. aureus and S. pyogenes ... 

Macrolide resistance is mediated by the erm gene in other antibiotic-producing bacteria such as Streptomyces spp. [152-159], Micromonospora sp. [160], Sac-charopolyspora sp. [161], and Arthwbacter sp. [162], all of which have, together with cooperative determinants, coding for a transport ATPase. The resistance in all of these bacteria has been described in detail [116]. 

Enterohemorrhagic Escherichia coli (EHEC) 0157 H7 causes serious hemorrhagic colitis, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome in humans. Verotoxins produced by EHEC are the pathogens of these diseases. Two different verotoxins have been reported, VTl and VT2, that destroy mucosa and renal epithelium. The effect of macrolides at sub-MIC concentration was reported on the production of verotoxin (VT) by E. coli 0157. Nakata et al observed that the production of VTl was suppressed up to 10 hr when bacteria were incubated with 1/100 of MIC of CAM [83]. The production of VTl reached the control level after 22 hr even with 1/10 of MIC of CAM. On the other hand, production of VT2 was completely suppressed by 22 hr with 1/10 of MIC. This effect was observed when E. coli 0157 was incubated with EM. In contrast to the macrolides, ampicillin at sub-MIC levels did not inhibit the production of both VTl and VT2. To clarify the mechanism of suppression of VT production by macrolides, a macrolide-resistant gene of a S. pneumonia strain, the ermAM gene, encoding an enzyme of methylation of 23S RNA was transformed into an... 

Nakamura, A., Naito, Y, Nakazawa, K., Ohara, K., and Sawai, T. (2000). Selective suppression of aminoglycoside 3 -phosphoiylating enzyme activities by macrolides—A study by using macrolide-resistant bacteria. Jpn. J. Antibiot. 53 (Suppl. A), 28-31. 

Drug action and drug resistance in bacteria Macrolide antibiotics and lincomycin". Ed. S. Mitsuhashi, University Park Press, Baltimore, Maryland. 1972. 

The concerns over selection for resistance in commensal bacteria have been borne out in clinical studies where the majority of patients carry resistant organisms after treatment over a period of months. While macrolide resistance has become so common that this in itself is tolerable in certain settings, the fact that macrolide resistance is often carried on multi-resistance plasmids makes it more problematic. The official consensus has, therefore, been to avoid the promotion of macrolides for inflammation. However, in certain indications their use is so beneficial that concerns over resistance have been put aside by individual practitioners. 

The combined intrinsic activities of different efflux pumps play a major role for the intrinsic resistance of Gram-negative bacteria to macrolides and oxazolidi-nones as well as to the intrinsic resistance of Pseudomonas aeruginosa against a broad range of disinfectants and antibiotics. 

Resistance can occur via plasmid-mediated meth-ylation of the receptor site which reduces the binding of the macrolide. Also plasmid-mediated esterase activity, especially in coliform bacteria, can inactivate the macrolides. 

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... 

Macrolides inhibit growth of bacteria by inhibiting protein synthesis on ribosomes. Bacterial resistance to macrolides is often accompanied by cross-resistance to lincosamide and sireptogramin B antibiotics (MLS-resistance), which can be either inducible or constitutive. 14-Membered... 

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