体外诱导铜绿假单胞菌对亚胺培南和美罗培南耐药性的比较

In vitro induction of drug resistance in pseudomonas aeruginosa to imipenem vs meropenem

目的通过体外诱导铜绿假单胞菌对亚胺培南和美罗培南产生耐药,比较两者产生耐药的时间,分析哪种药更易诱导铜绿假单胞菌产生耐药。方法收集20株对所有抗生素均敏感的铜绿假单胞菌和20株质控菌株,先用肉汤培养,连续传代7次,再用肉汤稀释法测出其平均抑制浓度(MIC),然后按MIC/2配制亚胺培南和美罗培南浓度。肉汤中分别加入配制的亚胺培南和美罗培南,培养观察其耐药性,如耐药性增加,测出其MIC值,取MIC/2值浓度,继续培养至完全耐药。结果质控铜绿假单胞菌在用亚胺培南平均4d后就产生耐药,用美罗培南平均16d后产生耐药;患者铜绿假单胞菌在用亚胺培南平均3d后就产生耐药,用美罗培南平均15d后才产生耐药。结论质控铜绿假单胞菌和患者铜绿假单胞菌对亚胺培南产生耐药的平均时间远小于对美罗培南产生耐药的平均时间,亚胺培南比美罗培南更容易诱导铜绿假单胞菌产生耐药。

Objective To investigate the in vitro induction of drug resistance in pseudomonas aeruginosa to imipenem and meropenem, and based on the time to successful induction, determine which of the two antimicrobials is more readily to show drug resistance. Methods Pseudomonas aeruginosa isolated from patients （20 strains） and another 20 strains of quality controls, both sensitive to common antibiotics, were incubated with broth and subjected to growth for 7 consecutive passages. The minimal inhibition concentrations （MIC） were determined with broth dilution method. Solution of imipenem or meropenem was prepared based on half MIC and then added into the broth. Drug resistance was assessed days later, and when increased, new MIC was determined for the broth to be exposed to new preparations of half-MIC imipenem or meropenem until complete development of antibiotic resistance. Results It took a mean of 4 days for control pseudomonas aeruginosa strains to develop resistance to imipenem vs a mean of 16 days to meropenem. Pseudomonas aeruginos from patients became resistant to imipenem in a mean of 3 days and to meropenem in a mean of 15 days. Conclusion Quality control strains of pseudomonas aeruginosa and pseudomonas aeruginosa from patients gained resistance to imipenem earlier than they did to meropenem. Imipenem appeared more readily to show resistance compared with meropenem.