akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.


Up To Date などから基本を復習です
ちな、Vancomycin-dependent enterococci (VDE) という単語知りませんでした。


beta-lactamase resistance
aminoglycosides resistance
trimethoprim-sulfamethoxazole resistance
VCM resistance
LZD resistance
Daptomycin resistance
Quinupristin-dalfopristin resistance
Tigecycline resistance

Enterococci can develop resistance through mutations as well as acquisition of new genes on plasmids and transposons that can cross species and genera. Many of the acquired resistances likely emerged among enterococci colonizing humans or animals that were given antibiotics for other reasons.

●Enterococci have intrinsic resistance to many beta-lactam compounds, particularly cephalosporins. Ampicillin resistance in Enterococcus faecalis can be caused by penicillinase, which can be overcome with the addition of a beta-lactamase inhibitor. Enterococcus faecium is intrinsically resistant to ampicillin due to the presence of a low-affinity penicillin-binding protein and thus is not susceptible to beta-lactamase–inhibitor combinations.
●Enterococci have intrinsic low to moderate level of resistance to aminoglycosides, but gentamicin and streptomycin retain synergistic activity against enterococci when combined with a cell wall agent. When high-level resistance to one of these aminoglycosides is present (eg, through ribosomal mutations or acquisition of modifying enzymes), the synergistic effect of that agent is eliminated. 
●Although enterococci may be susceptible in vitro to trimethoprim-sulfamethoxazole, they seem to be resistant in vivo due to their capacity to utilize preformed folic acid. 
●Resistance to vancomycin develops through alteration of its binding site, the D-alanyl-D-alanine terminus of cell wall precursors. Production of D-alanyl-D-lactate–ending peptidoglycans, for which vancomycin has significantly reduced affinity, confers high-level vancomycin resistance, primarily seen in E. faecium. The vancomycin–resistance gene clusters that encode high-level resistance can disseminate to other bacterial species.
●Enterococcal resistance to linezolid is acquired through mutation and possibly enzyme modification of the ribosomal RNA target. The emergence of resistance is generally associated with the heavy use of linezolid, although resistant enterococci have been isolated from patients without previous exposure to the antibiotic. The emergence of linezolid resistance in enterococci through transferable plasmids carrying the cfr gene raises concern of spreading linezolid resistance to other strains and species. 
●Resistance to daptomycin has been reported after prolonged daptomycin exposure. The mechanism of resistance involves mutations in genes associated with the regulation of the cell envelope response to antibiotics and cell membrane phospholipid metabolism. Clinical failure of daptomycin in endocarditis due to enterococci with apparent in vitro susceptibility to the drug has been reported.
●E. faecalis are naturally resistant to quinupristin-dalfopristin due to the presence of the lsa gene, which encodes a putative adenosine triphosphate–binding efflux protein. Resistance to quinupristin-dalfopristin among E. faecium can occur by enzyme modification, hydrolysis, active transport, and target modification. Resistance to dalfopristin alone dramatically reduces efficacy of the combined antibiotic and decreases the bactericidal effect. 
●Certain special tests are recommended for evaluating resistances of enterococci that are difficult to detect with standard laboratory methods. Susceptibility testing at a high inoculum can better detect penicillin and ampicillin resistance.