Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

中文翻译：

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QPX7728（一种超广谱β-内酰胺酶抑制剂）的体内活性与β-内酰胺类药物合用，可抵抗耐碳青霉烯的肺炎克雷伯菌。

对β-内酰胺类药物的耐药性已经引起了主要的临床问题。QPX7728是一种新型的超广谱环状硼酸β-内酰胺酶抑制剂，具有针对丝氨酸和金属-β-内酰胺酶的活性，开发用于解决这种耐药性，可与β-内酰胺类抗生素联合使用。这些研究的目的是评估QPX7728与多种β-内酰胺类药物在中性粒细胞减少症小鼠大腿感染模型中对耐碳青霉烯类肺炎克雷伯菌的分离物的活性。在8 mg / L QPX7728存在的情况下，中性粒细胞减少症小鼠感染了增强型β-内酰胺MIC≤2 mg / L的品系。两株对碳青霉烯类耐药的肺炎克雷伯菌每2小时分别用氨曲南，比阿培南，头孢吡肟，头孢他啶，头孢洛嗪和美罗培南或与12.5、25或50 mg / kg体重的QPX7728组合测试24小时。单独使用所有β-内酰胺类药物进行抑菌或使细菌生长。QPX7728加这些β-内酰胺中的每一个的组合在所有测试的QPX7728剂量下均能杀死细菌。总体而言，这些数据表明，与不同的伴侣β-内酰胺类抗生素联合使用的QPX7728可能在治疗因碳青霉烯耐药的肺炎克雷伯菌而引起的细菌感染中有用。