title: In vitro antibacterial activity of vertilmicin and its susceptibility to modifications by the recombinant AAC6'-APH2'' enzyme.
abstract: 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 MIC(90)s of vertilmicin were in the range of 0.5 to 8 microg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC(50)s and/or MIC(90)s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC(90)s, 16 microg/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.
authors: Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Cong-Ran
authors: CR
authors: Li
authors: Xin-Yi
authors: XY
authors: Yang
authors: Ren-Hui
authors: RH
authors: Lou
authors: Wei-Xin
authors: WX
authors: Zhang
authors: Yue-Ming
authors: YM
authors: Wang
authors: Min
authors: M
authors: Yuan
authors: Yi
authors: Y
authors: Li
authors: Hui-Zhen
authors: HZ
authors: Chen
authors: Bin
authors: B
authors: Hong
authors: Cheng-Hang
authors: CH
authors: Sun
authors: Li-Xun
authors: LX
authors: Zhao
authors: Zhuo-Rong
authors: ZR
authors: Li
authors: Jian-Dong
authors: JD
authors: Jiang
authors: Xue-Fu
authors: XF
authors: You
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000617:Aminoglycosides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D004269:DNA, Bacterial; D005839:Gentamicins; D011994:Recombinant Proteins; C487733:vertilmicin; C108453:6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase; D000123:Acetyltransferases; D017853:Phosphotransferases (Alcohol Group Acceptor)