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Antimicrobial Agents and Chemotherapy, January 2004, p. 203-208, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.203-208.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Shana M. Gunderson,1 Robert A. Hayes,2 John P. Quinn,2,3 and Larry H. Danziger1*

Department of Pharmacy Practice, The University of Illinois at Chicago,1 Division of Infectious Disease, Cook County Hospital,2 Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois3

Received 17 March 2003/ Returned for modification 7 July 2003/ Accepted 7 October 2003

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 µg/ml); ß-lactamase-positive and ß-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 µg/ml); and ß-lactamase-positive and ß-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 µg/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.

* Corresponding author. Mailing address: The University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice (M/C 886), 833 South Wood St., Chicago, IL 60612. Phone: (312) 996-0892. Fax: (312) 413-1797. E-mail: Danziger{at}uic.edu.

Antimicrobial Agents and Chemotherapy, January 2004, p. 203-208, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.203-208.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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