Enterococcal species can cause a variety of infections, including urinary tract infections, bacteremia, endocarditis, and meningitis. The antimicrobial agents available for treatment of enterococcal infection are reviewed here, followed by treatment approaches for clinical syndromes caused by enterococci. Other issues related to enterococci are discussed in detail separately. (See "Mechanisms of antibiotic resistance in enterococci" and "Epidemiology, prevention and control of vancomycin-resistant enterococci" and "Microbiology of enterococci".)
Approach to susceptible strains — Compared with most streptococci, enterococci are relatively resistant to penicillin and ampicillin; even when these cell wall–active agents inhibit enterococci, they often do not kill them, and vancomycin is even less bactericidal. Enterococcus faecium isolates are more resistant to penicillin than E. faecalis (minimum inhibitory concentration for 90 percent of strains [MIC90] >16 mg/mL versus 2 to 4 mcg/mL, respectively); MICs for ampicillin are usually 1 dilution lower than those of penicillin. Piperacillin activity is similar to that of penicillin, and imipenem has some activity against E. faecalis. Cell wall–active agents with limited or no activity against enterococci include nafcillin, oxacillin, ticarcillin, ertapenem, most cephalosporins, and aztreonam.
Enterococci are also relatively impermeable to aminoglycosides, and the serum concentrations of aminoglycosides required for bactericidal activity are much higher than can be achieved safely in humans. However, the simultaneous use of a cell wall–active agent raises the permeability of the cell so that an intracellular bactericidal aminoglycoside concentration can be achieved without excessive toxicity . Bactericidal activity is warranted in clinical circumstances of life-threatening infection. (See 'Clinical infections' below.)
Enterococcal isolates are usually tested for susceptibility to ampicillin, penicillin, and vancomycin. Although found only rarely, the presence of beta-lactamase confers resistance to penicillin and ampicillin when large numbers of organisms are present (eg, endocarditis vegetation), even though the organism may test susceptible using standard laboratory inocula. Thus, to rule out this possibility for endocarditis or other life-threatening enterococcal infections, such as meningitis, some experts recommend that the isolate be screened for beta-lactamase production with nitrocefin, a chromogenic cephalosporin, even if ampicillin susceptible.
Traditionally, the standard of care for enterococcal endocarditis has been a cell wall–active agent combined with an aminoglycoside to generate synergistic, bactericidal activity. When an aminoglycoside is used, the enterococcal isolates should be tested for high-level resistance to gentamicin and streptomycin. If the organism is reported as susceptible to high levels of an aminoglycoside ("SYN-S" indicates "susceptible to synergism"), then it is assumed that synergism will be achieved when that aminoglycoside is combined with ampicillin. Strains that are resistant to high levels of gentamicin are resistant to synergism with tobramycin, netilmicin, and amikacin as well as gentamicin, but some of these strains lack high-level resistance to streptomycin and these will demonstrate synergism with that agent [2,3]. (See 'Clinical infections' below.)