title: Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. IV. Aminoglycoside-modifying enzyme AAC(6')/APH(2") is responsible for arbekacin-resistance enhanced by bleomycin.
abstract: Resistance patterns against various antimicrobial agents including beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides were examined for 58 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from April to November 1992. All the MRSA strains produced type II-coagulase but not beta-lactamase. Regarding aminoglycoside-modifying enzymes, 7 strains (12%) appeared to be producing aminoglycoside 4',4"-adenyltransferase AAD(4',4") encoded by aadD without coproduction of bifunctional aminoglycoside 6'-acetyltransferase/2"-phosphotransferase AAC(6')/APH(2") encoded by aacA-aphD (referred to as tobramycin-resistant type, TOBr). The remaining 51 strains (88%) were phenotypically producers of both enzymes (i.e., mix-resistant type, Mixr). AAD(4',4"), encoded by aadD which was reported to be closely linked with bleomycin (BLM)-resistance determinant, could be seen in 100% MRSA strains and ca. 90% strains expressed AAC(6')/APH(2"). BLM endowed Mixr-type but not TOBr-type MRSA strain with enhanced resistance to arbekacin (ABK) dose-dependently, presumably by modifying the production of AAC(6')/APH(2"). The manifestation of ABK-resistant phenotype by Mixr-type MRSA required the coexistence of BLM. Therefore, ABK must be administered carefully to cure MRSA infection in patients who have been treated with BLM.
authors.affiliation: Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inouye
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Takesue
authors.forename: T
authors.initials: T
authors.lastname: Santo
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001761:Bleomycin / Q000494:pharmacology*; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001761:Bleomycin; D003982:Dibekacin; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase; C031986:arbekacin