Montero Abelardo, Ariza Javier, Corbella Xavier, Doménech Alejandro, Cabellos Carmen, Ayats Josefina, Tubau Fe, Borraz Carmen, Gudiol Francesc
Laboratory of Experimental Infection, Infectious Disease Service, Hospital de Bellvitge, University of Barcelona, Spain.
J Antimicrob Chemother. 2004 Dec;54(6):1085-91. doi: 10.1093/jac/dkh485. Epub 2004 Nov 16.
Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model.
We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively.
In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone.
Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.
已有报道称用黏菌素成功治疗了耐碳青霉烯类鲍曼不动杆菌菌株，但最近我们反对将其作为单一疗法使用，因为在小鼠肺炎模型中取得的效果不佳。我们的目的是确定在同一模型中有效的抗生素联合疗法。
我们使用了两株耐碳青霉烯类鲍曼不动杆菌菌株（菌株D和E；亚胺培南的最低抑菌浓度分别为8和512mg/L）。两株菌株对妥布霉素、利福平及黏菌素的最低抑菌浓度分别为8、8和0.5mg/L。
在由菌株D引起的感染中，肺部细菌计数（log(10)cfu/g，均值±标准差）为：对照组（10.86±0.25）、亚胺培南组（5.99±0.59，与对照组相比P<0.05）及黏菌素组（10.43±1.09）；亚胺培南+妥布霉素是最有效的联合用药（5.46±0.62，与对照组相比P<0.05）。在由菌株E引起的感染中，结果如下：对照组（10.82±0.33）、利福平组（5.62±0.26，与对照组相比P<0.05）、黏菌素组（8.38±1.22，与对照组相比P<0.05）及亚胺培南组（11.01±0.2）；利福平+亚胺培南（3.79±0.99）和利福平+妥布霉素（3.96±0.30）是最有效的联合用药（P<0.05）；利福平+黏菌素（5.59±1.17）的结果与单用利福平相似。
我们的数据表明，对于亚胺培南耐药水平中等的耐碳青霉烯类鲍曼不动杆菌感染，亚胺培南仍是最佳选择，最好与氨基糖苷类联合使用。对于对亚胺培南高度耐药的菌株，如果对利福平仅为中度耐药，利福平与亚胺培南、妥布霉素或黏菌素联合使用可能有效。
