Servicio de Microbiología, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, 28007 Madrid, Spain
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Abstract |
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Introduction |
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Materials and methods |
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We tested a total of 302 S. pneumoniae. The clinical isolates were non-duplicate, consecutive and recently obtained in our laboratory from lower respiratory tract infections and blood cultures during the period 19981999. Among these, 98 were penicillin-susceptible, 124 were penicillin intermediate (MIC 0.121 mg/L) and 80 were penicillin resistant (MIC 2 mg/L). Twenty-eight per cent (86) of the isolates were also erythromycin resistant (MIC
1 mg/L), and a total of 44 isolates (14%) were resistant or had intermediate susceptibility to ciprofloxacin (MIC 24 mg/L). We also tested a total of 300 non-duplicate, consecutive, recently obtained clinical isolates of H. influenzae [234 ß-lactamase-negative and 66 (22%) ß-lactamase-positive] and 28 M. catarrhalis (75% ß-lactamase-positive) from lower respiratory tract infections and blood cultures during 19981999.
Determination of MICs
Susceptibility testing was performed by the broth microdilution method following the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS).9 The NCCLS breakpoint for ciprofloxacin against H. influenzae (1 mg/L) was also used for S. pneumoniae and M. catarrhalis.9 We used commercially prepared dried microdilution panels (SB-265805 surveillance MIC1 and MIC2, Baxter, MicroScan RUO/IUO, Sacramento, CA, USA) manufactured for this study. The panels included gemifloxacin at two-fold increases in concentration from 0.001 to 256 mg/L, trovafloxacin, grepafloxacin, levofloxacin and ciprofloxacin at two-fold increases in concentration from 0.015 to 16 mg/L, and ofloxacin at two-fold increases in concentration from 0.06 to 64 mg/L. Panels were inoculated with isolates suspended in cation-adjusted MuellerHinton broth with 3% lysed horse blood for S. pneumoniae and M. catarrhalis, and Haemophilus Test Medium for H. influenzae, to achieve a final inoculum of 47 x 105 cfu/mL. Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, H. influenzae ATCC 49247 and S. pneumoniae ATCC 49619 were used as control strains in each run. MIC readings were taken after incubation at 35°C for 2024 h in air.
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Results and discussion |
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Gemifloxacin is a new fluoroquinolone with improved activity against Gram-positive microorganisms. Several studies have determined the activity of this compound against the most common respiratory tract pathogens.6,7,10 Our results are similar to those found in other studies and show that gemifloxacin is highly active against S. pneumoniae, H. influenzae and M. catarrhalis. The in vitro activity of gemifloxacin against S. pneumoniae appeared to be independent of penicillin and erythromycin susceptibility, and in all cases MICs of gemifloxacin were <0.25 mg/L. Against H. influenzae, gemifloxacin was four-fold more active against ß-lactamase-negative isolates; however, the MIC90 of gemifloxacin against ß-lactamase-positive isolates was 0.03 mg/L. Other studies have shown no differences in the activity of gemifloxacin against ß-lactamase-positive or -negative strains.7 The results found in our study may be explained by the fact that the MICs of ciprofloxacin against the population of ß-lactamase-positive strains studied were higher than those against the ß-lactamase-negative strains. In the case of M. catarrhalis, the activity of gemifloxacin was independent of ß-lactamase production. Other reports have demonstrated MICs slightly lower than ours.7 Gemifloxacin retained good activity against S. pneumoniae with diminished susceptibility to ciprofloxacin.
The use of newer fluoroquinolones against respiratory tract pathogens diversifies the number of treatments and potentially contributes to decreasing the spread of resistance to other antimicrobial agents by reducing the selective pressure on other antibiotic groups. Gemifloxacin (SB-265805) is a potent new fluoroquinolone with excellent activity against respiratory tract pathogens, including strains with resistance to current antimicrobial therapies.
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Acknowledgments |
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Notes |
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References |
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2
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Liñares, J., de la Campa, A. G. & Pallarés, R. (1999). Fluoroquinolone resistance in Streptococcus pneumoniae. New England Journal of Medicine 341, 15467.
3 . Felmingham, D. & Washington, J. (1999). Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogensfindings of the Alexander Project 19921996. Journal of Chemotherapy 11, Suppl. 1, 521.[ISI][Medline]
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Chen, D. K., McGeer, A., de Azavedo, J. C. & Low, D. E. (1999). Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network. New England Journal of Medicine 341, 2339.
5 . Johnson, D. M., Jones, R. N. & Erwin, M. E. (1999). Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines. Diagnostic Microbiology and Infectious Diseases 33, 8791.[ISI][Medline]
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Hardy, D., Amsterdam, D., Mandell, L. A. & Rotstein, C. (2000). Comparative in vitro activities of ciprofloxacin, gemifloxacin, grepafloxacin, moxifloxacin, ofloxacin, sparfloxacin, trovafloxacin, and other antimicrobial agents against bloodstream isolates of gram-positive cocci. Antimicrobial Agents and Chemotherapy 44, 8025.
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Davies, T. A., Kelly, L. M., Hoellman, D. B., Ednie, L. M., Clark, C. L., Bajaksouzian, S. et al. (2000). Activities and postantibiotic effects of gemifloxacin compared to those of 11 other agents against Haemophilus influenzae and Moraxella catarrhalis. Antimicrobial Agents and Chemotherapy 44, 6339.
8 . Wise, R., Gee, T., Andrews, J. & Marshall, G. (2000). The pharmacokinetics and inflamatory fluid penetration of gemifloxacin. In Program and Abstracts of the Fortieth Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 2000. Abstract 657, p. 20. American Society for Microbiology, Washington, DC.
9 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibilty Tests for Bacteria that Grow AerobicallyFifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
10 . Sucari, A., Vilches, V., Scarano, S., Stepanik, D., Sarachian, B., Mikaelian, G. et al. (1999). In vitro activity of gemifloxacin against Gram-positive and Gram-negative clinical isolates in Argentina. In Program and Abstracts of the Thirty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 1999. Abstract 1491, p. 265. American Society for Microbiology, Washington, DC.
Received 30 August 2000; returned 30 November 2000; revised 2 January 2001; accepted 30 January 2001