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 (MIC50) were ≥128 and 32 µg/ml for isolates obtained from 1978 to 1984 and from 1985 to 1989, respectively, and 0.5 µg/ml for isolates obtained from 1990 to 2002. The MIC90 of gentamicin was consistently ≥128 µg/ml. Investigation of the occurrence of AME revealed that the MIC50 of gentamicin was highly correlated with the presence of aac(6′)/aph(2″) encoding aminoglycoside acetyl/phosphotransferase. The MIC50 of arbekacin was 2 µg/ml for strains isolated in 1978–1984 and ≤0.5 µg/ml for strains isolated from 1985 to 2002. The MIC90 of arbekacin was 8 µg/ml for the strains isolated in 1978–1989 and 1 to 2 µg/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 MIC90 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.