Emergence and management of drug-resistant enterococcal infections

Abstract

The treatment of multidrug-resistant enterococcal infections continues to be a challenge for clinicians. Glycopeptide and β-lactam resistance is now a common feature of the majority of Enterococcus faecium hospital isolates, and resistance to aminoglycosides, quinupristin–dalfopristin, linezolid and daptomycin further complicates the problem. New antibiotics, such as tigecycline, lipoglycopeptides (dalbavancin, oritavancin and telavancin) and cephalosporins with activity against Enterococcus faecalis (ceftobiprole and ceftaroline), may have potential activity against certain resistant enterococcal strains in specific clinical settings, as may some older antibiotics, such as ampicillin, chloramphenicol, doxycycline, minocycline and nitrofurantoin. However, the treatment of endovascular infections (particularly endocarditis, where bactericidal therapy is important for optimal cure rates) caused by resistant enterococci continues to be an immense challenge even with the availability of new agents. The optimal therapy for these infections is not well established and clinical data are usually limited to case reports with conflicting results. Therefore, treatment decisions may have to be based on animal models and sporadic experiences and the best approach is for the physician to consider carefully each patient on a case by case manner and gather all the clinical and microbiological information possible regarding species identification and susceptibilities in order to choose a therapeutic regimen that would appear to be active.

Keywords::

• Enterococcus spp.
• resistance
• therapy
• vancomycin resistance

Financial & competing interests disclosure

C Arias has received lecture fees and grant support from Pfizer and Merck. B Murray has grant support from Johnson & Johnson, Astellas and Intercell and has served as consultant for Astellas, Theravance, Cubist, Targanta, Johnson & Johnson and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^*Only Enterococcus faecium.

^‡If ampicillin MIC is up to 64 mg/l, cautious use of high-dose ampicillin could be considered.

^§Generally considered only for Enterococcus faecalis.

^¶Doses of 8 mg/kg and above might be preferred.

^#FDA approval only for vancomycin-susceptible E. faecalis in complicated skin and soft-tissue infections.

^**Lower urinary tract infections only.

^‡‡Anectodal cases and animal models only.

^§§May occasionally be active in vitro and could be considered in combination with other agents.

^¶¶Not active against VanA-type enterococci.

^##Limited activity.

^***Selection of E. faecalis with increased oritavancin MIC mutants was obtained in vivo.

^‡‡‡Only E. faecalis.

^§§§In vitro data only.

VRE: Vancomycin-resistant enterococci.