Can amikacin be useful for high-level gentamicin-resistant (HLGR) enterococci ?
HLGR (MICs > =512 mg/L) is almost always mediated by a bifunctional aminoglycoside modifying enzyme, AAC(6′)-APH(2″); it remains the only mechanism of HLGR reported in the UK. This enzyme confers resistance to all aminoglycosides licensed in the UK, except streptomycin. Arbekacin, which is available in Japan, is a poor substrate and retains activity against some HLGR strains. HLGR abolishes the synergic bactericidal activity expected of aminoglycosides combined with cell wall-active agents (penicillins or glycopeptides). Screening with amikacin can lead to confusion; some HLGR isolates may not appear highly resistant in vitro even though synergy would be abolished. Thus gentamicin and streptomycin are the best aminoglycosides to test against most enterococci. Note, however, that non-HLGR E. faecalis isolates should also be screened for high-level kanamycin resistance, if amikacin is preferred over gentamicin in your hospital; HLKR again precludes synergy with amikacin combinations.
