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Antimicrobial Agents and Chemotherapy, July 1999, p. 1560-1564, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activity of Moxifloxacin, Administered Once a Day, against Streptococcus pneumoniae in an In Vitro Pharmacodynamic Model of Infection

Alasdair P. MacGowan,* Karen E. Bowker, Mandy Wootton, and H. Alan Holt

Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Bristol, United Kingdom

Received 12 May 1998/Returned for modification 24 December 1998/Accepted 8 April 1999

The antibacterial effect of moxifloxacin was studied by using an in vitro pharmacodynamic model of infection with dosing simulations of 400 mg every 24 h for 48 h. Streptococcus pneumoniae was tested by using four wild-type strains for which the moxifloxacin MICs were 0.008, 0.12, 0.14, and 3.6 mg/liter. In addition, two isogenic mutants, generated from the strains for which the moxifloxacin MICs were <= 0.12 mg/liter and for which the MICs were 1.0 and 1.6 mg/liter, were also used. Antibacterial efficacy was measured by the following indices: log change in viable count at 12, 24, 36, and 48 h; area under the bacterial kill curve (AUBKC); and time to kill 99.9% of the initial inoculum. With the three strains for which the moxifloxacin MICs were <= 0.14 mg/liter, there was a marked reduction in viable count over 12 to 36 h; in contrast, with strains for which the MICs were >= 1.0 mg/liter, little killing occurred over 48 h. A sigmoid dose-response model indicated that the area under the curve/MIC ratio was strongly related to the log change in viable count at 24 and 48 h and to the AUBKC. These data indicate that moxifloxacin may have a role in management of S. pneumoniae infection.

* Corresponding author. Mailing address: Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol, BS10 5NB, United Kingdom. Phone: 44 (0) 117 9595652. Fax: 44 (0) 117 9593154. E-mail: MACGOWAN_A{at}southmead.swest.nhs.uk.

Antimicrobial Agents and Chemotherapy, July 1999, p. 1560-1564, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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