In vitro antibacterial activity of vertilmicin and its susceptibility to modifications by the recombinant AAC6'-APH2'' enzyme.
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.
Li
Cong-Ran
CR
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yang
Xin-Yi
XY
Lou
Ren-Hui
RH
Zhang
Wei-Xin
WX
Wang
Yue-Ming
YM
Yuan
Min
M
Li
Yi
Y
Chen
Hui-Zhen
HZ
Hong
Bin
B
Sun
Cheng-Hang
CH
Zhao
Li-Xun
LX
Li
Zhuo-Rong
ZR
Jiang
Jian-Dong
JD
You
Xue-Fu
XF
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
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)