Trends in the gentamicin and arbekacin susceptibility of methicillin-resistant Staphylococcus aureus and the genes encoding aminoglycoside-modifying enzymes.

It is generally accepted that methicillin-resistant Staphylococcus aureus (MRSA) is also resistant to aminoglycoside antibiotics. We investigated trends of gentamicin and arbekacin susceptibilities and the prevalence of the genes encoding aminoglycoside-modifying enzymes (AMEs) for a total of 218 strains of MRSA isolated from blood specimens obtained from 1978 through 2002 in one hospital. The minimum inhibitory concentrations of gentamicin at which 50% of the strains were inhibited (MIC(50)) were > or =128 and 32 microg/ml for isolates obtained from 1978 to 1984 and from 1985 to 1989, respectively, and 0.5 microg/ml for isolates obtained from 1990 to 2002. The MIC(90) of gentamicin was consistently > or =128 microg/ml. Investigation of the occurrence of AME revealed that the MIC(50) of gentamicin was highly correlated with the presence of aac(6')/aph(2'') encoding aminoglycoside acetyl/phosphotransferase. The MIC(50) of arbekacin was 2 microg/ml for strains isolated in 1978-1984 and </=0.5 microg/ml for strains isolated from 1985 to 2002. The MIC(90) of arbekacin was 8 microg/ml for the strains isolated in 1978-1989 and 1 to 2 microg/ml for strains isolated in 1990-2002. Though it has been established that AAC(6')/APH(2'') modifies arbekacin, the trend of arbekacin resistance was not necessarily consistent with the presence of this enzyme. However, the prevalence of both aac(6')/aph(2'') and aph(3')-III in the strains isolated from 1978 through 2002 was correlated with the MIC(90) values of arbekacin. Thus, it is most likely that APH(3')-III, in addition to AAC(6')/APH(2''), is somehow involved in arbekacin resistance in S. aureus. Our results imply that gentamicin- and arbekacin-resistant MRSAs have consistently decreased for the past 25 years and that this finding is, most likely, attributable to the declining prevalence of genes encoding for AMEs.