Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters
Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters
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DOI：
10.1093/jac/dkp425
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发表时间：
2010-02-01
影响因子：
5.2
通讯作者：
Livermore, David
中科院分区：
文献类型：
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作者：
Mushtaq, Shazad;Warner, Marina;Livermore, David
我们测试了 BAL30072（一种新型铁载体单菌素）对铜绿假单胞菌、洋葱伯克霍尔德菌群和不动杆菌属多重耐药临床分离株的活性。 MIC 是在补充了 2,2' 联吡啶以诱导铁转运的 Mueller-Hinton 琼脂上测定的；比较剂为氨曲南、亚胺培南、美罗培南和哌拉西林/他唑巴坦。BAL30072 对鲍曼不动杆菌具有显着的活性，200 种产生碳青霉烯酶的菌株中，有 73% 的菌株具有显着活性，其中大多数属于英国主导的 OXA-23 克隆 1 和 SE 克隆谱系，在 1 mg/L 浓度下敏感，在 8 mg/L 浓度下敏感，为 89%。然而，在这些克隆的一些代表中发现了抗性，并且在代表其他鲍曼不动杆菌克隆的分离株中更常见。从囊性纤维化 (CF) 中分离出来的 50 株洋葱伯克霍尔德杆菌复合体中，68% 对 1 mg/L 的 BAL30072 敏感，78% 对 8 mg/L 的 BAL30072 敏感，而只有 22% 对 8 mg/L 的氨曲南敏感。针对铜绿假单胞菌的活性良好，但不太显着，50 个（大多数为多重耐药）CF 分离株中有 36% 在 8 mg/L 浓度下敏感，而 12% 对 8 mg/L 氨曲南敏感。 BAL30072 在 8 mg/L 浓度下对产生 11/19 金属-β-内酰胺酶的铜绿假单胞菌具有活性，而氨曲南的活性为 3/19（16 mg/L 浓度下为 12/19 与 8/19）。对铜绿假单胞菌突变体、分离株和转接合子的研究表明，BAL30072 受到外排、AmpC 和一些不常见的获得性 β-内酰胺酶（包括一些超广谱 OXA 类型和 PER-1）的影响。BAL30072 对许多产生碳青霉烯酶的鲍曼不动杆菌表现出令人印象深刻的活性，特别是针对英国最流行的两个克隆，以及针对鲍曼不动杆菌。 CF 中分离出 cepacia 复合体；它对铜绿假单胞菌的活性比氨曲南更强。
We tested the activity of BAL30072, a novel siderophore monobactam, against multiresistant clinical isolates of Pseudomonas aeruginosa, Burkholderia cepacia group and Acinetobacter spp. and against laboratory P. aeruginosa strains with defined resistance mechanisms.MICs were determined on Mueller-Hinton agar supplemented with 2,2' bipyridyl to induce iron transport; comparators were aztreonam, imipenem, meropenem and piperacillin/tazobactam.BAL30072 was strikingly active against Acinetobacter baumannii, with 73% of 200 carbapenemase-producing isolates, most of them belonging to the UK-dominant OXA-23 clone 1 and SE clone lineages, susceptible at 1 mg/L and 89% at 8 mg/L. Resistance nevertheless was seen in a few representatives of these clones and appeared commoner among isolates representing other A. baumannii clones. Sixty-eight per cent of 50 B. cepacia complex isolates from cystic fibrosis (CF) were susceptible to BAL30072 at 1 mg/L and 78% at 8 mg/L, compared with only 22% susceptible to aztreonam at 8 mg/L. Activity against P. aeruginosa was good, though less dramatic, with 36% of 50 (mostly multiresistant) CF isolates susceptible at 8 mg/L, compared with 12% susceptible to aztreonam at 8 mg/L. BAL30072 was active against 11/19 metallo-beta-lactamase-producing P. aeruginosa at 8 mg/L compared with 3/19 for aztreonam (12/19 versus 8/19 at 16 mg/L). Studies on P. aeruginosa mutants, isolates and transconjugants showed that BAL30072 was affected by efflux, AmpC and by a few uncommon acquired beta-lactamases, including some extended-spectrum OXA types and PER-1.BAL30072 displayed impressive activity against many carbapenemase-producing A. baumannii, particularly against the two clones most prevalent in the UK, and also against B. cepacia complex isolates from CF; it was more active than aztreonam against P. aeruginosa.