Comparative in-vitro and in-vivo activity of AM-1155 against anaerobic bacteria

Abstract

The in-vitro activity of AM-1155, a 6-fluoro-8-methoxy quinolone, was compared with those of temafloxacin, sparfloxacin, tosufloxacin, ciprofloxacin, ofloxacin and cefmetazole, a cephamycin, against a variety of anaerobic bacteria. Although AM-1155 demonstrated only modest activity against the Bacteroides fragilis group and Prevotella bivia (MIC90s > or =3.13 mg/mL), 76% of the B. fragilis strains tested were inhibited at AM-1155 concentrations of 0.78 mg/L. AM-1155 was highly active against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp., Clostridium perfringens and Mobiluncus spp. (MIC90s < or =0.39 mg/L). An in-vivo study using a mixed infection with AM-1155- and tosufloxacin-susceptible B. fragilis and Escherichia coli strains in rat granuloma pouch was performed. AM-1155 was effective against both organisms whereas tosufloxacin was effective only against E. coli. These results correlated well to the higher pouch levels of AM-1155 than those of tosufloxacin. Clostridium difficile overgrowth was found in the caecum of mice treated with ampicillin both 1 and 7 days after 5 days dosing, but not in AM-1155-treated mice. These results suggest that the clinical efficacy of AM-1155 against infections involving most anaerobic bacteria except for the B. fragilis group and P. bivia should be evaluated further.

Gatifloxacin Ophthalmic Solution for Treatment of Bacterial Conjunctivitis: Safety, Efficacy and Patient Perspective

“…Hosaka used gatifloxacin (called AM-1155 in this paper) as an antimicrobial agent against a broad spectrum of microbes including Staphylococcus aureus, P. aeruginosa and N. gonorrhoeae 2. Kato used AM-1155 against a broad range of anaerobic organisms including Clostridium species 16. These organisms were clinical isolates, the exception being the Bacteroides fragillis group.…”

In vitro activity of gatifloxacin tested against anaerobic bacteria by reference agar dilution and Etest methods

“…Infections caused by anaerobic bacteria have been refractory to therapy by fluoroquinolones commonly used in the last decade [1]. In contrast, newer (trovafloxacin) and investigational (BAY 12–8039, SB‐265805 or LB20304, gatifloxacin, clinafloxacin) fluoroquinolones possess greater activity against these species, enabling clinical use [2, 3]. Gatifloxacin, formerly AM‐1155 or CG5501, is a new 8‐methoxy‐fluoroquinolone with a wide spectrum of activity against aerobic Grampositive cocci and Gram‐negative bacilli [4–7], that also has high bioavailability that could justify a susceptibility breakpoint of ≤2 mg/L [8].…”

“…Other anaerobes or related fastidious facultative anaerobes reported as susceptible to gatifloxacin were Mobiluncus spp. (MIC 90 , 0.20 mg/L) and Gardenerella vaginalis (MIC 90 , 1.56 mg/L) [2].…”

In Vitro Antianaerobic Activity of DX-619, a New Des-Fluoro(6)Quinolone

“…DX-619 showed potent activity against Bacteroides, Prevotella, Fusobacterium, Micromonas, Actinomyces, and Clostridium spp., with MIC 50 s/MIC 90 s of <0.03 to 0.25/<0.03 to 1 g/ml, respectively. DX-619 was also active against imipenem-resistant Bacteroides spp., with MIC 50 s/MIC 90 s of 0.25/1 g/ml, respectively.Older fluoroquinolones, such as ciprofloxacin and ofloxacin, are inactive or only partially active against anaerobic bacteria (7,11,12,15,20,23,25,26). Newer quinolones, such as sparfloxacin and levofloxacin (LVX), have improved in vitro activities against anaerobic bacteria but still have limited activities against certain gram-positive and gram-negative anaerobic bacilli (3,7,8,11,12,15,23,25).…”

“…Newer quinolones, such as sparfloxacin and levofloxacin (LVX), have improved in vitro activities against anaerobic bacteria but still have limited activities against certain gram-positive and gram-negative anaerobic bacilli (3,7,8,11,12,15,23,25). Some of the newer fluoroquinolones are much more active to both gram-positive and gram-negative anaerobic bacteria (3,8,11,12,15,20,26). DX-619 is a new derivative of quinolone, defined as a des-F (6) quinolone that lacks the six-position fluorine characteristic of the previous generation of fluoroquinolones.…”