Department of Genetic Engineering, Genomics Laboratory, SRM University, Chennai, India.
Indian J Med Res. 2018 Jan;147(1):97-101. doi: 10.4103/ijmr.IJMR_1407_16.
BACKGROUND & OBJECTIVES: New Delhi metallo-β-lactamase 1 (NDM-1) cleaves the beta-lactam ring, and confers bacterial resistance against most of the beta-lactam antibiotics, except tigecycline and colistin. Among these two antibiotics, colistin is considered toxic, and therefore, its clinical use and dosage need cautious approach. In the present study, six organic acids were screened individually and in combination of two acids for their effectiveness against NDM-1 Escherichia coli and a combination of colistin and oxalic or succinic acid was tested to find out the potential of combination therapy for reducing the dose of toxic colistin.
Antibacterial activity of the organic acid and their combinations was tested by disc diffusion method against NDM-1 E. coli, and minimum inhibitory concentration (MIC) was determined by broth dilution method. Synergistic effect between organic acids and colistin was tested by checkerboard method.
Oxalic acid showed the highest zone of inhibition (15±1 mm) followed by succinic acid, tartaric acid, fumaric acid, citric acid and malic acid. The combination of two acids did not increase the zone of inhibition significantly. MIC was found to be the lowest with oxalic acid and succinic acid (320 μg/ml). In the presence of 160 μg/ml oxalic acid or succinic acid, MIC of colistin was reduced from 8 to 4 μg/ml, indicating synergistic effect.
INTERPRETATION & CONCLUSIONS: Our findings showed that combination therapy using colistin and oxalic acid or succinic acid might find safe clinical application of this antibiotic in controlling infections due to NDM-1 bacteria.
新德里金属β-内酰胺酶 1（NDM-1）可切断β-内酰胺环，使细菌对大多数β-内酰胺类抗生素产生耐药性，而替加环素和黏菌素除外。这两种抗生素中，黏菌素被认为具有毒性，因此其临床应用和剂量需要谨慎。在本研究中，我们单独筛选了 6 种有机酸，并将两种酸组合使用，以评估它们对 NDM-1 大肠杆菌的效果，同时还测试了黏菌素与草酸或琥珀酸的组合，以寻找降低毒性黏菌素剂量的联合治疗潜力。
采用纸片扩散法检测有机酸及其组合对 NDM-1 大肠杆菌的抗菌活性，并用肉汤稀释法测定最小抑菌浓度（MIC）。采用棋盘法检测有机酸与黏菌素之间的协同作用。
草酸的抑菌圈最大（15±1mm），其次是琥珀酸、酒石酸、富马酸、柠檬酸和苹果酸。两种酸的组合并未显著增加抑菌圈的大小。MIC 值最低的是草酸和琥珀酸（320μg/ml）。在 160μg/ml 草酸或琥珀酸存在的情况下，黏菌素的 MIC 值从 8μg/ml 降低至 4μg/ml，表明存在协同作用。
我们的研究结果表明，黏菌素与草酸或琥珀酸联合治疗可能为这种抗生素在控制 NDM-1 细菌感染方面的安全临床应用提供依据。
