[Molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species].
OBJECTIVE
To investigate the molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species.


METHODS
Non-repetitive 90 carbapenem-resistant strains of Acinetobacter species were collected in Beijing, Guangzhou, and Fuzhou 1999-2004. The homology of the isolates was determined by both pulsed field gel electrophoresis and randomly amplified polymorphic DNA typing. Seven representative clones were selected from the 90 strains of Acinetobacter isolated from different hospitals to be used for further study. Analytical isoelectric focusing was used to measure the isoelectric point of the beta-lactamase. Plasmid DNA was extracted and purified Genes of different beta-lactamase, including bla(TEM--), bla(SHV-), bla(PER-), blaI(MP-), bla(VIM-), and bla(OXA-) genes, in these clone strains were amplified and sequenced. PCR was used to analyze the integrons.


RESULTS
The P clone strain isolated during an outbreak of pan-drug-resistant Acinetobacter species in Peking Union Medical College Hospital 2004 was not susceptible to most common antimicrobial agents tested. The 7 representative clones produced multiple beta-lactamases: TEM-1, high-level AmpC, SHV-type, OXA-23 carbapenemase and IMP-8 and metalloenzyme respectively. One clone produced PER-1 enzyme. These 7 clone strains were resistant to most beta-lactams (including carbapenems), erythromycin, chloramphenicol, and rifampin. Two clone strains were susceptible to cefoperazone/sulbactam and amikacin while 4 clone strains susceptible to levofloxacin. All of the 7 clones were susceptible to minocycline and colistin. Five different integrons were found, harboring the genes mediating the resistance to aminoglycosides, rifampin, chloramphenicol, and carbapenems (bla(IMP-8)).


CONCLUSIONS
The molecular bases of multiple-drug or pan-drug resistance in Acinetobacter species include production of OXA-23 carbapenemase or IMP type metalloenzyme and integrons with different resistance gene cassettes. Pan-drug-resistant Acinetobacter species are susceptible to old antimicrobials agents, such as colistin and minocycline.
Wang
Hui
H
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Sun
Hong-li
HL
Ning
Yong-zhong
YZ
Yang
Qi-wen
QW
Chen
Min-jun
MJ
Zhu
Yuan-jue
YJ
Xu
Ying-chun
YC
Xie
Xiu-li
XL
D000150:Acinetobacter / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D000151:Acinetobacter Infections / Q000382:microbiology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002681:China; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D019105:Random Amplified Polymorphic DNA Technique; D001618:beta-Lactamases / Q000235:genetics
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D015378:Imipenem; D001618:beta-Lactamases