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Antimicrobial Agents and Chemotherapy, November 2008, p. 3875-3882, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01400-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vitro Antibacterial Activity of Vertilmicin and Its Susceptibility to Modifications by the Recombinant AAC(6')-APH(2'') Enzyme

Cong-Ran Li, Xin-Yi Yang, Ren-Hui Lou, Wei-Xin Zhang, Yue-Ming Wang, Min Yuan, Yi Li, Hui-Zhen Chen, Bin Hong, Cheng-Hang Sun, Li-Xun Zhao, Zhuo-Rong Li, Jian-Dong Jiang,^* and Xue-Fu You^*

Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received 30 October 2007/ Returned for modification 23 February 2008/ Accepted 3 August 2008

Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to that of netilmicin except for a methyl group at the C-6' position. In the present study, the in vitro antibacterial activity of vertilmicin was studied, and its susceptibility to modifications by the recombinant aminoglycoside bifunctional modifying enzyme AAC(6')-APH(2'') was compared with those of verdamicin and netilmicin. A total of 1,185 clinical isolates collected from hospitals in Beijing between 2000 and 2001 were subjected to the in vitro antibacterial activity evaluations, including MIC, minimum bactericidal concentration (MBC), and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin-resistant strains, respectively. For most of the non-gentamicin-resistant bacteria (except for the isolates of Pseudomonas spp.), the MIC₉₀s of vertilmicin were in the range of 0.5 to 8 µg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC₅₀s and/or MIC₉₀s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC₉₀s, 16 µg/ml, for the gram-positive gentamicin-resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis. Meanwhile, vertilmicin was a potent bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for Escherichia coli, Klebsiella pneumoniae, and S. aureus and 1 to 4 for S. epidermidis. The time-kill curve determination further demonstrated that this effect was rapid and concentration dependent. In evaluations of susceptibility to modifications by the recombinant AAC(6')-APH(2'') with maximum rate of metabolism/K_m measurements, vertilmicin exhibited susceptibilities to both acetylation and phosphorylation lower than those of netilmicin and verdamicin.

Published ahead of print on 18 August 2008.

C.-R.L. and X.-Y.Y. made equal contributions to the work.