Zheng Jifang, Liu Qiang, Wang Haoran, Huo Fengmin, Jia Junnan, Huang Hairong, Chen Suting
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Institute, Capital Medical University, Beijing, China.
Microbiol Spectr. 2025 Feb 4;13(2):e0177724. doi: 10.1128/spectrum.01777-24. Epub 2024 Dec 27.
Given the intrinsic resistance of to a wide range of conventional antibiotics, it is urgent to explore new therapeutic approaches to manage this infection effectively. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a proton pump inhibitor, has shown good bacteriostatic activity against . This study aimed to determine its synergistic antimicrobial effects when combined with commonly used antibiotics. The reference strain and 39 clinical isolates were collected. The minimum inhibitory concentration and fractional inhibitory concentration index were determined for the combined treatment using CCCP with various antibiotics including clarithromycin, amikacin, linezolid, bedaquiline, and clofazimine. A time-killing assay was used to measure the effect of the combined drug regimens quantitatively. The simultaneous use of CCCP with traditional antibiotics shows a synergistic effect across a wide range, significantly boosting the ability to inhibit the growth of throughout its growth phases. When CCCP is used in combination with clarithromycin, amikacin, and linezolid, it produces a synergistic effect on both the standard strain and most clinical isolates. When CCCP is paired with bedaquiline and clofazimine, it exhibits additive effects. Moreover, high levels of CCCP in combination with other antibiotics were found to rapidly eradicate the bacteria. The use of CCCP as a potential treatment for infections shows promising results, especially when combined with other antibiotics to achieve a potent bactericidal effect.IMPORTANCE poses a significant public health threat due to its intrinsic resistance to a broad spectrum of conventional antibiotics. This resistance necessitates urgently exploring novel therapeutic strategies to effectively combat infections caused by this pathogen. Our previous research has identified carbonyl cyanide-3-chlorophenylhydrazone (CCCP) as a potent direct antimicrobial agent against and as an enhancer of clarithromycin activity. Our results demonstrate that the concurrent administration of CCCP with traditional antibiotics exhibits a synergistic effect across a wide range, which could be crucial for overcoming the challenges posed by infections. Furthermore, the use of high concentrations of CCCP in combination with other antibiotics was found to rapidly eliminate , suggesting a potential therapeutic advantage. These insights not only advance our understanding of antimicrobial synergy but also hold promise for the development of more effective treatment regimens against drug-resistant infections.
鉴于[病原体名称]对多种传统抗生素具有内在抗性，迫切需要探索新的治疗方法来有效控制这种感染。羰基氰3-氯苯腙（CCCP）是一种质子泵抑制剂，已显示出对[病原体名称]具有良好的抑菌活性。本研究旨在确定其与常用抗生素联合使用时的协同抗菌效果。收集了[病原体名称]参考菌株和39株临床分离株。测定了CCCP与包括克拉霉素、阿米卡星、利奈唑胺、贝达喹啉和氯法齐明在内的各种抗生素联合治疗时的最低抑菌浓度和部分抑菌浓度指数。采用时间杀菌试验定量测定联合用药方案的效果。CCCP与传统抗生素同时使用显示出广泛的协同作用，显著增强了在[病原体名称]整个生长阶段抑制其生长的能力。当CCCP与克拉霉素、阿米卡星和利奈唑胺联合使用时，对标准菌株和大多数临床分离株均产生协同作用。当CCCP与贝达喹啉和氯法齐明配对时，表现出相加作用。此外，发现高浓度的CCCP与其他抗生素联合可迅速根除细菌。将CCCP用作[病原体名称]感染的潜在治疗方法显示出有希望的结果，特别是与其他抗生素联合使用以实现强效杀菌效果时。重要性[病原体名称]由于其对广泛的传统抗生素具有内在抗性，对公共卫生构成重大威胁。这种抗性使得迫切需要探索新的治疗策略来有效对抗由该病原体引起的感染。我们之前的研究已确定羰基氰-3-氯苯腙（CCCP）是一种针对[病原体名称]的强效直接抗菌剂，也是克拉霉素活性的增强剂。我们的结果表明，CCCP与传统抗生素同时给药显示出广泛的协同作用，这对于克服[病原体名称]感染带来的挑战可能至关重要。此外，发现高浓度的CCCP与其他抗生素联合可迅速清除[病原体名称]，表明具有潜在的治疗优势。这些见解不仅推进了我们对抗菌协同作用的理解，也为开发针对耐药性[病原体名称]感染的更有效治疗方案带来了希望。
