Escribano I, Rodríguez J C, Llorca B, García-Pachon E, Ruiz M, Royo G
Section of Microbiology, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain.
Chemotherapy. 2007;53(6):397-401. doi: 10.1159/000109769. Epub 2007 Oct 12.
Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid.
We studied the mutations in gyrA and gyrB genes and the influence of efflux pump systems with 2 inhibitors (reserpine and MC 207.110).
The effect of the active efflux system on the decrease in sensitivity to ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin, gatifloxacin and linezolid was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. These inhibitors exhibit activity both in strains that are resistant and in strains that are susceptible to these antibiotics. However, they are seen to be most active in resistant strains, since the minimum inhibitory concentration of the antibiotics studied in these strains was reduced between 2- and 6-fold.
Therefore, these mechanisms are involved in the resistance to both compounds. It would be of interest to carry out further studies to determine to what extent these active efflux systems influence resistance to the different groups of drugs used in the treatment of tuberculosis, with a view to the possibility of using the inhibitors of these systems in future therapeutic applications.
我们的目的是研究外排泵系统对结核分枝杆菌对氟喹诺酮类和利奈唑胺耐药性的影响。
我们研究了gyrA和gyrB基因的突变以及两种抑制剂(利血平和MC 207.110)对外排泵系统的影响。
通过研究这些化合物与利血平和MC 207.110联合检测时体外活性的变化,研究了主动外排系统对环丙沙星、莫西沙星、左氧氟沙星、氧氟沙星、加替沙星和利奈唑胺敏感性降低的影响。这些抑制剂在耐药菌株和对这些抗生素敏感的菌株中均表现出活性。然而,它们在耐药菌株中活性最高,因为在这些菌株中所研究抗生素的最低抑菌浓度降低了2至6倍。
因此,这些机制与对这两种化合物的耐药性有关。开展进一步研究以确定这些主动外排系统在多大程度上影响对用于治疗结核病的不同药物组的耐药性,以期未来在治疗应用中使用这些系统的抑制剂,这将是很有意义的。