Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois 60515, USA.
Pharmacotherapy. 2010 Apr;30(4):354-60. doi: 10.1592/phco.30.4.354.
To better define the utility of surrogate markers for doripenem susceptibility relative to gold standard microbiology tests.
In vitro experiment.
Large tertiary-care academic medical center. ORGANISMS: One hundred twenty-five randomly selected, unique clinical isolates of Acinetobacter baumannii collected between 2005 and 2008.
In vitro activity of doripenem, imipenem, and meropenem was examined by agar dilution, and the carbapenem-hydrolyzing oxacillinase gene, bla(OXA), status was determined by polymerase chain reaction for clinical isolates of A. baumannii. Positive predictive values for doripenem susceptibility were evaluated according to imipenem susceptibility, meropenem susceptibility, the doripenem Etest, and bla(OXA) gene status. Imipenem had the greatest activity against all A. baumannii isolates tested (51% susceptible), followed by meropenem and doripenem (44% and 29% susceptible, respectively). The positive predictive value for doripenem susceptibility was 68% with meropenem susceptibility by agar dilution, 56% with imipenem susceptibility by agar dilution, and 82% with the doripenem Etest. Doripenem Etest susceptibilities yielded eight major errors when compared with agar dilution. The bla(OXA) genes were present in 52 isolates (42%). Expression of either bla(OXA-23) or bla(OXA-40) was 100% predictive of resistance to doripenem, imipenem, and meropenem. In isolates not harboring bla(OXA) genes, 49% were susceptible to doripenem. Among the 125 isolates, carbapenem discordance existed in 22% (28 isolates), all of which were susceptible to imipenem but not to doripenem.
In the A. baumannii isolates tested in this study, the doripenem Etest resulted in eight susceptibility misclassifications yet remained the most accurate predictor of doripenem susceptibility. The bla(OXA) genes in A. baumannii appeared to confer resistance against doripenem, imipenem, and meropenem and may be the best existing surrogate marker to accurately predict resistance to these drugs. Further study is necessary to better characterize the full genotypic carbapenem resistance profile of A. baumannii relative to newer carbapenem agents, such as doripenem.
更好地定义替代标志物对多利培南敏感性的效用，相对于金标准微生物学测试。
体外实验。
大型三级保健学术医疗中心。
2005 年至 2008 年间随机选择的 125 种独特的鲍曼不动杆菌临床分离株。
通过琼脂稀释法检测多利培南、亚胺培南和美罗培南的体外活性，并通过聚合酶链反应确定鲍曼不动杆菌临床分离株的碳青霉烯水解酶基因 bla（OXA）状态。根据亚胺培南敏感性、美罗培南敏感性、多利培南 E 试验和 bla（OXA）基因状态，评估多利培南敏感性的阳性预测值。所有测试的鲍曼不动杆菌分离株中，亚胺培南的活性最强（51%敏感），其次是美罗培南和多利培南（分别为 44%和 29%敏感）。琼脂稀释法的美罗培南敏感性对多利培南敏感性的阳性预测值为 68%，琼脂稀释法的亚胺培南敏感性为 56%，多利培南 E 试验为 82%。与琼脂稀释法相比，多利培南 E 试验有 8 次主要错误。52 株（42%）分离株中存在 bla（OXA）基因。bla（OXA-23）或 bla（OXA-40）的表达 100%可预测对多利培南、亚胺培南和美罗培南的耐药性。在未携带 bla（OXA）基因的分离株中，49%对多利培南敏感。在 125 株分离株中，22%（28 株）存在碳青霉烯类药物不一致性，所有这些分离株均对亚胺培南敏感，但对多利培南不敏感。
在本研究中测试的鲍曼不动杆菌分离株中，多利培南 E 试验导致 8 次药敏分类错误，但仍然是预测多利培南敏感性的最准确指标。鲍曼不动杆菌中的 bla（OXA）基因似乎对多利培南、亚胺培南和美罗培南产生耐药性，可能是准确预测这些药物耐药性的最佳现有替代标志物。需要进一步研究以更好地描述鲍曼不动杆菌相对于新型碳青霉烯类药物（如多利培南）的全基因型碳青霉烯类耐药谱。
