Activities and postantibiotic effects of gemifloxacin compared to those of 11 other agents against Haemophilus influenzae and Moraxella catarrhalis

Abstract

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, </=0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, </=0.125 microgram/ml) and amoxicillin-clavulanate (MICs </=4.0 microgram/ml) were active, followed by cefuroxime (MICs, </=16.0 microgram/ml); azithromycin MICs were </=4.0 microg/ml. For nine H. influenzae isolates with reduced quinolone susceptibilities, the MICs at which 50% of isolates are inhibited (MIC(50)s) were 0.25 microgram/ml for gemifloxacin and 1.0 microgram/ml for the other quinolones tested. All strains had mutations in GyrA (Ser84, Asp88); most also had mutations in ParC (Asp83, Ser84, Glu88) and ParE (Asp420, Ser458), and only one had a mutation in GyrB (Gln468). All quinolones tested were equally active (MICs, </=0.06 microgram/ml) against 50 M. catarrhalis strains; amoxicillin-clavulanate, cefixime, cefuroxime, and azithromycin were very active. Against 10 H. influenzae strains gemifloxacin, levofloxacin, sparfloxacin, and trovafloxacin at 2x the MIC and ciprofloxacin at 4x the MIC were uniformly bactericidal after 24 h, and against 9 of 10 strains grepafloxacin at 2x the MIC was bactericidal after 24 h. After 24 h bactericidal activity was seen with amoxicillin-clavulanate at 2x the MIC for all strains, cefixime at 2x the MIC for 9 of 10 strains, cefuroxime at 4x the MIC for all strains, and azithromycin at 2x the MIC for all strains. All quinolones except grepafloxacin (which was bactericidal against four of five strains) and all ss-lactams at 2x to 4x the MIC were bactericidal against five M. catarrhalis strains after 24 h; azithromycin at the MIC was bactericidal against all strains after 24 h. The postantibiotic effects (PAEs) against four quinolone-susceptible H. influenzae strains were as follows: gemifloxacin, 0.3 to 2.3 h; ciprofloxacin, 1.3 to 4.2 h; levofloxacin, 2.8 to 6.2 h; sparfloxacin, 0.6 to 3.0 h; grepafloxacin, 0 to 2.1 h; trovafloxacin, 0.8 to 2.8 h. At 10x the MIC, no quinolone PAEs were found against the strain for which quinolone MICs were increased. Azithromycin PAEs were 3.7 to 7.3 h.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 1

Results of time-kill studies for 10 H. influenzae strains that exhibited decreases of 1 (□), 2 (■), or 3 () log 10 CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Only five ß-lactamase-negative strains were tested with ampicillin and amoxicillin.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.

FIG. 2

Results of time-kill studies for five M. catarrhalis strains that exhibited decreases of 1 (□), 2 (■), or 3 (), log₁₀ CFU/ml compared to the numbers at time zero. *, the lowest multiple of the MIC that resulted in the observed killing for the most strains is indicated above each bar. Because all strains were ß-lactamase positive, amoxicillin and ampicillin were not tested.