In-vitro and in-vivo potency of five new fluoroquinolones against anaerobic bacteria

Abstract

The MICs of difloxacin (A-56619), A-56620 and ofloxacin were similar or within one to two-fold dilutions against a variety of anaerobic bacteria. Ciprofloxacin was slightly less active (two- to four-fold dilutions) than difloxacin, A-56620 and ofloxacin. Norfloxacin was less active than the other fluoroquinolones tested against anaerobic bacteria. The MICs of norfloxacin, A-56620, ciprofloxacin and ofloxacin against most anaerobes, except the Gram-positive cocci, were lower at pH 8.1 than at pH 6.6. MICs of the fluoroquinolones against anaerobic cocci were the same at pH 6.6, 7.3 and 8.1. Norfloxacin and ciprofloxacin were most affected by the acidic pH. Ofloxacin and A-56620 were affected to a lesser extent by an acidic pH than norfloxacin and ciprofloxacin. The potency of difloxacin was similar at the three pHs tested. A subcutaneous anaerobic infection model in mice was used to determine the in-vivo efficacy of the new fluoroquinolones against Bacteroides fragilis. Difloxacin was the most potent compound in this test.

Increased activity of a new chlorofluoroquinolone, BAY y 3118, compared with activities of ciprofloxacin, sparfloxacin, and other antimicrobial agents against anaerobic bacteria

“…Only imipenem and metronidazole were active against all anaerobes. Overall, BAY y 3118 was more active than ciprofloxacin, sparfloxacin, piperacillin, cefotaxime, and clindamycin against the test isolates.Newer fluoroquinolone antimicrobial agents such as ciprofloxacin, ofloxacin, norfloxacin, lomefloxacin, and pefloxacin have been shown to have good activity against aerobic bacteria but usually have poor activity against most anaerobes, particularly the Bacteroides fragilis group (1,3,6,7,11 Our results confirm and extend the data regarding the in vitro activity of BAY y 3118 against anaerobes, particularly against those in the B. fragilis group. In the present study, we identified 5 of 435 (1%) anaerobes which were resistant (MICs of .4 ,ug/ml) to BAY y 3118; all were strains of the B. fragilis group.…”

Structure-activity relationships of the fluoroquinolones

“…It also has excellent pharmacokinetic properties (27). The N-1-fluoro-substituted phenyl substitution may improve the in vitro efficacy of quinolones against anaerobic bacteria, as exemplified by tosufloxacin (17), difloxacin (18), and temafloxacin (28).…”

In vitro activity of Bay Y3118 against anaerobic bacteria

“…Activity against the Bacteroides fragilis group organisms has been poor, in general (2,4,5,8,9,15,18). Variable activity against Prevotella species, such as the Prevotella melaninogenica and Prevotella oralis group, and against Bacteroides ureolyticus has been reported (8).…”