Aaron S D, Ferris W, Henry D A, Speert D P, Macdonald N E
Department of Medicine, University of Ottawa, Ontario, Ottawa, Canada.
Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1206-12. doi: 10.1164/ajrccm.161.4.9907147.
Most Burkholderia cepacia strains are resistant to many, or all, of the antibacterial agents commonly used in cystic fibrosis (CF), and selection of appropriate antibiotics for treatment of pulmonary exacerbations is therefore difficult. We developed a technique for rapid in vitro testing of multiple antibiotic combinations for B. cepacia isolates. For each of 119 multi-drug-resistant isolates of B. cepacia, our multiple combination bactericidal test (MCBT) studied the bactericidal activity of 10 to 15 antimicrobial agents using 225 +/- 97 single, double, and triple antibiotic combinations. Of the 119 isolates, 50% were resistant to all single antibiotics tested, 8% were resistant to all two-drug antibiotic combinations, but all were inhibited by at least one bactericidal triple-drug combination. When used alone, meropenem, ceftazidime and high-dose tobramycin (200 microg/ml) were bactericidal against only 47, 15, and 14% of in vitro isolates, respectively. Using a double antibiotic combination improved bactericidal activity; meropenem-minocycline, meropenem-amikacin, and meropenem-ceftazidime combinations were bactericidal against 76, 73, and 73% of isolates, respectively. However, 47% of isolates demonstrated antagonism (growth of an organism when a second antibiotic was added to a bactericidal single antibiotic). Triple antibiotic combinations that contained tobramycin, meropenem, and an additional antibiotic were most effective, and were bactericidal against 81 to 93% of isolates. We conclude that triple-antibiotic combinations are more likely than double and single antibiotic combinations to be bactericidal against B. cepacia in vitro. MCBT testing is a useful technique to help clinicians decide on appropriate nonantagonistic combination antibiotic therapy for patients with CF infected with B. cepacia.
大多数洋葱伯克霍尔德菌菌株对囊性纤维化（CF）中常用的许多或所有抗菌药物耐药，因此，为治疗肺部病情加重选择合适的抗生素很困难。我们开发了一种对洋葱伯克霍尔德菌分离株进行多种抗生素组合快速体外测试的技术。对于119株多重耐药的洋葱伯克霍尔德菌分离株，我们的多重组合杀菌试验（MCBT）使用225±97种单药、双药和三药抗生素组合研究了10至15种抗菌药物的杀菌活性。在这119株分离株中，50%对所有测试的单药抗生素耐药，8%对所有双药抗生素组合耐药，但所有分离株均被至少一种杀菌性三药组合抑制。单独使用时，美罗培南、头孢他啶和高剂量妥布霉素（200μg/ml）分别仅对47%、15%和14%的体外分离株有杀菌作用。使用双药抗生素组合可提高杀菌活性；美罗培南-米诺环素、美罗培南-阿米卡星和美罗培南-头孢他啶组合分别对76%、73%和73%的分离株有杀菌作用。然而，47%的分离株表现出拮抗作用（当在杀菌性单药抗生素中添加第二种抗生素时生物体生长）。含有妥布霉素、美罗培南和另一种抗生素的三药抗生素组合最有效，对81%至93%的分离株有杀菌作用。我们得出结论，在体外，三药抗生素组合比双药和单药抗生素组合更有可能对洋葱伯克霍尔德菌有杀菌作用。MCBT测试是一种有用的技术，可帮助临床医生为感染洋葱伯克霍尔德菌的CF患者决定合适的无拮抗作用的联合抗生素治疗方案。
