Activities and Postantibiotic Effects of Gemifloxacin Compared to Those of 11 Other Agents against
            <i>Haemophilus influenzae</i>
            and
            <i>Moraxella catarrhalis</i>

ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia. We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic commonly used for the treatment of pneumonia, through MIC determination and time-kill kinetic analysis. ABT-492 demonstrated potent activity against penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 g/ml); ␤-lactamase-positive and ␤-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 g/ml); and ␤-lactamase-positive and ␤-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 g/ml), with MICs being much lower than those of levofloxacin. Both ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates exposed to levofloxacin. Sigmoidal maximal-effect models support concentration-dependent bactericidal activity. The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both ABT-492 and levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for ABT-492 and one to six times the MIC for levofloxacin.

Section: Methodsmentioning

confidence: 99%

“…38:4298-4299, 2000). More importantly, quinolone resistance has been linked to therapeutic failure in the clinical setting (3,4,7). It is therefore crucial for researchers to design and develop potent antibacterial compounds to target all community-acquired respiratory pathogens, including those pathogens that are resistant to other antibacterials.…”

mentioning

confidence: 99%

In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis

Gunderson

Hayes

Quinn

et al. 2004

“…The inoculated test tubes were then placed in a shaking water bath at 35°C for an exposure period of 1 h. At the end of the exposure period, the cultures were diluted 1:1,000 in prewarmed broth to remove the antibiotic. An additional control culture containing bacteria and antibiotic at a concentration of 0.01 times the MIC was prepared to confirm that after dilution the antibiotic was no longer bacteriostatic (4,7).…”

Section: Methodsmentioning

confidence: 99%

“…PAE was determined by the viable plate count method (4) using freshly made HTM (7,11). The bacterial inoculum was prepared by suspending growth from an overnight chocolate agar plate in broth.…”

Section: Methodsmentioning

confidence: 99%

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 Compared to Their Susceptibilities to 11 Other Agents

Credito

Lin

Pankuch

et al. 2001

Self Cite

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% ␤-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 g/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 g/ml). Of the ␤-lactams, ceftriaxone had the lowest MICs (<0.004 to 0.016 g/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and <0.125 to 0.25 g/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 g/ml), and cefuroxime (0.25 to 8.0 g/ml). Amoxicillin was only active against ␤-lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 g/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. ␤-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with ␤-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. ␤-Lactam PAEs were similar and shorter than those of the ketolidemacrolide-azalide group for all strains tested.Although development of an effective vaccine against Haemophilus influenzae type b has led to the disappearance of the organism in many parts of the world, its place has been taken by untypeable H. influenzae strains. These organisms (followed by Streptococcus pneumoniae and Moraxella catarrhalis) are now considered to be the leading cause of acute exacerbations of chronic bronchitis and an important cause, together with S. pneumoniae and M. catarrhalis, of acute otitis media, sinusitis, and community-acquired respiratory tract infections (1,8,10,12,14,23).Current recommendations by the National Committee for Clinical Laboratory Standards (NCCLS) for use of Haemophilus test medium (HTM) for Haemophilus susceptibility testing (13) have been complicated by difficulty in commercial manufacture of this medium and its short half-life when made in house. Reliable Haemophilus susceptibility testing with HTM requires the use of freshly made medium within 3 weeks of manufacture (11,22 , abstr. 2136, 1999). This study further examined activity of ABT-773 against Haemophilus an...

“…Strains KD2221 and KD2222 contain an insertion of Ala between Gly-457 and Ala-458. Asterisks indicate that the indicated amino acid change has been associated previously with fluoroquinolone resistance (2,3,7,10,11,14). Strains KD2219, KD2220, and KD2221 were obtained from patients treated with quinolone; KD2222, KD2223, and KD2224 were from patients that received no quinolone.…”

mentioning

confidence: 99%

Quinolone-Resistant Haemophilus influenzae in a Long-Term-Care Facility: Nucleotide Sequence Characterization of Alterations in the Genes Encoding DNA Gyrase and DNA Topoisomerase IV

Li¹,

Mariano

Rahal

et al. 2004