Anti-<i>Brucella</i> Activity of Ro 23-9424, a Dual-Action Antibacterial

Abstract

The in vitro activity of dual-acting antibacterial Ro 23-9424 was determined by the agar dilution method against 126 clinical isolates of Brucella melitensis. It was compared with fleroxacin, ciprofloxacin and five conventional drugs. MIC₅₀ and MIC₉₀ for Ro 23-9424 were 1.0 and 4.0 mg/l, respectively, as compared with 0.25 and 0.5 mg/l for fleroxacin and ciprofloxacin. One strain which was resistant to other fluoroquinolones, with an MIC of > 8.0 mg/l, did not show cross-resistance to Ro 23-9424 and had an MIC of 4.0 mg/l. All the strains were susceptible to conventional drugs like gentamicin, streptomycin rifampicin, tetracycline and trimethoprim-sulfamethoxazole, with MICs ranging between 0.12 and 2.0 mg/l. Ro 23-9424 did not exhibit in vitro synergy with any of the conventional drugs.

Chemical and Biological Factors in the Control of Brucella and Brucellosis

“…Several antimicrobials, such as tetracycline, doxycycline, aminoglycosides, rifampicin, trimethoprim-sulfamethoxazole, quinolones, cephalosporins, chloramphenicol and macrolides, have been tested on laboratory animals and humans against brucellosis [4][5][6][7][8][9][10][11][12]. Monotherapies have produced unsatisfactory results.…”

“…doxycycline 100 mg twice/day for 45 days and streptomycin 1 g/day for 14 days or gentamicin 5-6 mg/Kg/d for 7 days) has proven to be the best treatment for the disease [10,13]. However, with relapses of 3-5% [10], plus serious side effects due to the tetracyclines, especially in children and pregnant women [4][5][6][7][8][9][10][11][12][13][14], there is the need to press on in search of new alternatives. Aminoglycosides are extremely active antimicrobial agents, particularly against bacteraemia caused by aerobic gram-negative bacilli [15].…”

“…Aminoglycosides are bactericidal antibiotics that show a high activity against Brucella in vitro [38,39]). However, the above-mentioned environmental factors related to the physical location of Brucella, may affect the bactericidal activity of the antibiotic.…”

“…Besides, the washing of cell monolayers to remove extracellular antibiotic, potentially underestimates antibiotic cell uptake since most antibiotics reemerge from the cell very rapidly during the washing procedure [50]. Other studies performed in fibroblasts had shown that after the incubation of high antibiotic concentrations (500 and 100 µg/mL) for several days, an 9 accumulation of the drug occurs with I/E ratios of 6. Therefore, very long incubation periods required for GEN accumulation would mean the maintenance of high circulating GEN concentrations.…”