Which antibiotics are effective against resistant enterococcal strains?

Updated: Jun 10, 2021
  • Author: Susan L Fraser, MD; Chief Editor: John L Brusch, MD, FACP  more...
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Answer

Less frequently used antibiotics (eg, quinupristin-dalfopristin, linezolid, daptomycin, tigecycline) with activity against many VRE strains have improved this situation, but resistance to these agents has already been described. A mutation (G2576U) in the domain V of the 23S rRNA is responsible for linezolid resistance, [5] whereas resistance to quinupristin-dalfopristin may be the result of several mechanisms: modification of enzymes, active efflux, and target modification. Resistance of E faecalis and E faecium to daptomycin, a cyclic lipopeptide antibiotic that acts on the bacterial cell membrane, has also been reported. [7]  Recently approved antibiotics such as eravacycline may provide treatment options in refractory cases.

It appears that the beta-lactam antibiotics ceftaroline, ertapenem, ampicillin, cefepime, and ceftriaxone can increase the in vitro activity of daptomycin against vancomycin-resistant E faecalis and E faecium. Ceftaroline and daptomycin appeared to be the most effective combination. [8] In a study of synergistic combinations against isolates resistant to daptomycin, a combination of daptomycin and ampicillin appeared to be the most synergistic. [9] The unavailability of clinical synergistic data for a specific isolate limits treatment to the mainstays of therapy against resistant enterococci, linezolid and daptomycin.

Six phenotypes of vancomycin resistance, termed VanA, VanB, VanC, VanD, VanE, and VanG, have been described. The VanA and VanB phenotypes are clinically significant and mediated by 1-2 acquired transferable operons that consist of 7 genes in 2 clusters termed VANA and VANB operons. In 1988, these gene clusters first were reported in enterococcal strains. VanA is carried on a transposon Tn1546 that is almost always plasmid-mediated.

In the United States and Europe, the 3 major phenotypes include VanA, VanB, and VanD. VanA is the most common, and enterococcal isolates exhibit high-level resistance to both vancomycin and teicoplanin, while VanB isolates have variable resistance to vancomycin and remain susceptible to teicoplanin. The VanC phenotype is mediated by the chromosomal VANC1 and VANC2 genes, which are constitutively present in E gallinarum (VANC1) and E casseliflavus (VANC2). These genes confer relatively low resistance levels to vancomycin and are not transferable. To date, the VanD, VanE, and VanG phenotypes have been described in only a few strains of enterococci.


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