a Microbiology Department, School of Medicine, Universidad Complutense, 28040 Madrid; b Medical Department, GlaxoSmithKline, Tres Cantos, Madrid, Spain
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Abstract |
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Introduction |
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This study explores the activity of five new quinolones against isolates with reduced susceptibility to ciprofloxacin, and the effect of the presence of human serum on the resistance rate.
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Materials and methods |
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Susceptibility was determined using a broth microdilution method. MICs and MBCs were measured using ToddHewitt broth as the culture medium. To evaluate the effect of the presence of human serum, MICs and MBCs were also determined using 80% human serum (from a serum pool obtained from healthy donors who had not undergone drug treatment in the previous month) and 20% ToddHewitt broth. The final inoculum was 5 x 105 cfu/mL. Cultures were incubated for 24 h at 35°C in 5% CO2. Strains were tested in triplicate, and modal MIC and MIC90 values were calculated. S. pneumoniae ATCC 49619 was used as the control strain. Percentages of resistance were calculated using the susceptibility breakpoints for levofloxacin (2 mg/L), trovafloxacin (
1 mg/L) and moxifloxacin (
1 mg/L) established by the NCCLS,6 a susceptibility breakpoint of
2 mg/L for ciprofloxacin (there being no NCCLS breakpoint)2 and a susceptibility breakpoint of
1 mg/L (similar to the value for new quinolones) for clinafloxacin and gemifloxacin.
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Results and discussion |
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Although other studies have concluded that the presence of human serum does not influence the intrinsic activity of some new quinolones,4,5 the results of this study suggest that this conclusion cannot be extended to all fluoroquinolones. Other authors have shown that serum has no influence on the resistance rates for moxifloxacin.5 For the other quinolones the influence of serum is significant for isolates with a ciprofloxacin MIC of 4 mg/L, since when the strains are tested in the presence of serum, the MIC measured exceeded the breakpoint. Differences from studies published previously4,5,8 could be the result of the fact that the percentage of serum used in this study (80%) is higher than that used before (up to 50% serum),4,8 and may be due to the MIC distribution of the strains tested. The effect of serum could not be attributed exclusively to protein binding since it is lower for ciprofloxacin (30%)9 than for moxifloxacin (50%),9 where the effect is not observed.
In conclusion, considering both factors (using strains with higher ciprofloxacin MICs and the presence of human serum), gemifloxacin and clinafloxacin exhibited the lowest MIC90 values (0.5 and 1 mg/L without and with serum, respectively) for the whole population of S. pneumoniae with ciprofloxacin MICs of 0.5 mg/L, and the lowest resistance rates (0 and
10% without and with serum, respectively). The other new quinolones (levofloxacin, trovafloxacin and moxifloxacin) exhibited resistance rates of
22% for the population tested, with less activity against strains with higher ciprofloxacin MICs.
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Acknowledgements |
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Notes |
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References |
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2
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García-Rey, C., Aguilar, L. & Baquero, F. (2000). Influences of different factors on prevalence of ciprofloxacin resistance in Streptococcus pneumoniae in Spain. Antimicrobial Agents and Chemotherapy 44, 33812.
3 . Fuentes, F., Giménez, M. J., Marco, F., Alou, L., Aguilar, L. & Prieto, J. (2000). In vitro susceptibility to gemifloxacin and trovafloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin. European Journal of Clinical Microbiology and Infectious Diseases 19, 1379.[ISI][Medline]
4 . Eliopoulos, G. M. (1995). In vitro activity of fluoroquinolones against gram-positive bacteria. Drugs 49, Suppl. 2, 4857.[Medline]
5 . Woodcock, J. M., Andrews, J. M., Boswell, F. J., Brenwald, N. P. & Wise, R. (1997). In vitro activity of BAY 12-8039, a new fluoroquinolone. Antimicrobial Agents and Chemotherapy 41, 1016.[Abstract]
6 . National Committee for Clinical Laboratory Standards. (2001). Performance Standards for Antimicrobial Susceptibility TestingEleventh Informational Supplement M100-S11. NCCLS, Wayne, PA.
7
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Ewing, S., Ruiz, M., Torres, A., Marco, F., Martínez, J. A., Sánchez. M. et al. (1999). Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. American Journal of Respiratory and Critical Care Medicine 159, 183542.
8 . Marchese, A., Debbia, E. A., Pesce, A. & Schito, G. C. (1996). Bactericidal activity, morphological alterations, and synergistic interactions of rufloxacin, a new fluoroquinolone, alone and in combination with its N-desmethylate d derivative (MF 922). Chemotherapy 42, 909.[ISI][Medline]
9
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Lister, P. D. & Sanders, C. C. (1999). Pharmacodynamics of levofloxacin and ciprofloxacin against Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy 43, 7986.
Received 8 March 2001; returned 26 June 2001; revised 10 July 2001; accepted 17 September 2001