Hiroshima Journal of Medical Sciences Volume 43 Issue 3
published_at 1994-09

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

Inouye Yoshio
Hashimoto Masayo
Takesue Yoshio
Santo Takahiro
Yokoyama Takashi
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HiroshimaJMedSci_43_87.pdf
Abstract
Resistance patterns against various antimicrobial agents including β-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 notβ-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.
Keywords
Methicillin-resistant Staphylococcus aureus (MRSA)
Antibiotic resistance
AAC(6’) I APH(2”)
Arbekacin
Bleomycin