Journal of Antimicrobial Chemotherapy (1999) 44, 761-766
© 1999 The British Society for Antimicrobial Chemotherapy
Exploration of the in-vitro pharmacodynamic activity of moxifloxacin for Staphylococcus aureus and streptococci of Lancefield Groups A and G
Bristol Centre for Antimicrobial Research and Evaluation, North Bristol NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK
The serum concentrations associated with the oral administration of 400 mg moxifloxacin every 24 h over 48 h in man were simulated in an in-vitro dilutional, continuous bacterial culture model of infection. The initial inoculum was 5 x 107–5 x 108 cfu/mL and all strains were tested on at least three occasions. Two strains of Staphylococcus aureus (one methicillin susceptible, the other resistant) with moxifloxacin MICs 0.14 mg/L and 0.06 mg/L and two strains of ß-haemolytic streptococci, Lancefield Group A, MIC 0.16 mg/L and Group G, MIC 0.4 mg/L were used. In addition, two laboratory-generated mutants with raised moxifloxacin MICs were also employed: methicillin-sensitive S. aureus (MSSA) MIC 1.0 mg/L and Group A streptococcus MIC 1.8 mg/L. The antibacterial effect of moxifloxacin was judged by changes in viable count over time, and the area under the bacterial-kill curve (AUBKC) after 24 and 48 h. For S. aureus MIC 0.14 mg/L the AUBKC24 (log cfu/mL.h) was 77.8 ± 4.6 and AUBKC48 92.0 ± 6.9. For its mutant, moxifloxacin MIC 1.0 mg/L, the AUBKC24 was 116.1 ± 15.6 and AUBKC48 211.9 ± 23.1, indicating decreased killing. AUBKC24 and AUBKC48 values of 110.7 ± 10.3 and 130.9 ± 21.3, respectively, were noted for the MRSA strain. The Group A streptococcus, MIC 0.16 mg/L, had an AUBKC24 of 91.4 ± 19.4 and AUBKC48 of 157.0 ± 70.9. The mutant, MIC 1.8 mg/L, had an AUBKC24 of 127.0 ± 1.9 and AUBKC48 of 205.1 ± 6.4. Despite a lower MIC (0.4 mg/L) the single strain of Group G streptococcus tested was killed poorly, AUBKC24 139.9 ± 3.6 and AUBKC48 252.3 ± 18.6. The pharmacodynamic parameters AUC/MIC, T > MIC, (AUC > MIC)/MIC (AUC = area under the curve, T = time) and WAUC ((AUC/MIC) (T > MIC/100)) (WAUC = weighted area under the curve) were related to AUBKC24 and AUBKC48 using an inhibitory sigmoid Emax model. T > MIC was poorly related to AUBKC (r = 0.36) while AUC/MIC, (AUC > MIC)/MIC and WAUC were strongly related to AUBKC24 (r = 0.75–0.79) and AUBKC48 (r = 0.78–0.84). The maximum antibacterial effect was achieved with an AUC/MIC ratio of 150–200. AUC-related pharmacodynamic parameters predicted antibacterial effect better than T > MIC.
* Corresponding author. Tel: +44-117-959-5652; Fax: +44-117-959-3154; E-mail: macgowan_a{at}southmead.swest.nhs.uk
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