Journal of Antimicrobial Chemotherapy (2001) 47, 681-684
© 2001 The British Society for Antimicrobial Chemotherapy
Brief report |
Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with other fluoroquinolones against respiratory tract pathogens
Servicio de Microbiología, Hospital General Universitario ‘Gregorio Marañón’, Dr. Esquerdo 46, 28007 Madrid, Spain
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Abstract |
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The in vitro activity of gemifloxacin (SB-265805) was compared with that of other fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300 clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L inhibited all microorganisms tested. MIC90 values of gemifloxacin, trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC90 values of the same fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L, respectively.
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Introduction |
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TopAbstractIntroductionMaterials and methodsResults and discussionReferences |
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Increasing resistance to antimicrobial agents among respiratory tract pathogens is a cause of concern. ß-Lactam-resistant strains of the three most common pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, are being isolated with increasing frequency in many countries, as well as macrolide- and fluoroquinolone-resistant strains of S. pneumoniae.1–4 Therefore, there is a need for new antimicrobials with activity against these microorganisms, since the efficacy of the antimicrobials commonly used in the therapy of respiratory tract infections is being compromised. New fluoroquinolones have been developed in an attempt to help improve this situation. Gemifloxacin (SB-265805) is a potent new fluoroquinolone, which has an oxime-derived (amino-methyl) pyrrolidine substituent at C7 conferring activity against Gram-positive and -negative microorganisms.5–7 The favourable pharmacokinetics of gemifloxacin make it a promising agent for the therapy of respiratory tract infections.8 The objective of this study was to determine the in vitro activity of gemifloxacin against recent clinical isolates of S. pneumoniae, H. influenzae and M. catarrhalis, and to compare it with that of other fluoroquinolones.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResults and discussionReferences |
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Bacterial strains
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 1998–1999. Among these, 98 were penicillin-susceptible, 124 were penicillin intermediate (MIC 0.12–1 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 2–4 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 1998–1999.
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 Mueller–Hinton 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 4–7 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 20–24 h in air.
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Results and discussion |
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TopAbstractIntroductionMaterials and methodsResults and discussionReferences |
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Gemifloxacin demonstrated the most potent antimicrobial activity among the quinolones tested against S. pneumoniae, H. influenzae and M. catarrhalis. The comparative in vitro antimicrobial activity of gemifloxacin and other fluoroquinolones is shown in the Table
. All 630 isolates were inhibited by gemifloxacin at 0.12 mg/L. MIC90s of gemifloxacin, trovafloxacin, grepafloxacin, levofloxacin and ofloxacin against all isolates tested were 0.03, 0.12, 0.12, 1 and 2 mg/L, respectively.
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Gemifloxacin had similar high activity against penicillin-susceptible and -resistant S. pneumoniae, erythromycin-resistant S. pneumoniae, and ß-lactamase-positive and -negative H. influenzae and M. catarrhalis. Against S. pneumoniae, gemifloxacin was two-fold more active than grepafloxacin and trovafloxacin, and 16-fold more active than levofloxacin. These results are similar to those found in other studies.6,10 Against H. influenzae, the activity of gemifloxacin was two-fold higher than that of grepafloxacin and trovafloxacin, and four-fold higher than that of levofloxacin. Against M. catarrhalis, the activity of gemifloxacin was similar to that of trovafloxacin, and four-fold higher than that of grepafloxacin and levofloxacin (Table
). Gemifloxacin was equally active against ß-lactamase-positive and -negative M. catarrhalis (MIC90 0.015 mg/L in both cases, data not shown in the Table). In the case of S. pneumoniae with reduced susceptibility to ciprofloxacin (MIC 2 mg/L), gemifloxacin showed excellent activity, although the MIC90 of gemifloxacin against those isolates was two-fold higher (0.06 mg/L) than that found against isolates susceptible to ciprofloxacin (0.03 mg/L). 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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This work was supported by a grant from SmithKline Beecham Pharmaceuticals. This study was presented in part at the Thirty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, USA, 26–29 September 1999.
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Notes |
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* Corresponding author. Tel: +34-91-586-8459; Fax: +34-91-504-4906; E-mail: ecercenado{at}teleline.es
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References |
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1 . Baquero, F., García-Rodríguez, J. A., García de Lomas, J. & Aguilar, L. (1999). Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a 1-year (1996–1997) multicenter surveillance study. The Spanish Surveillance Group for Respiratory Pathogens. Antimicrobial Agents and Chemotherapy 43, 357–9.
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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, 1546–7.
3 . Felmingham, D. & Washington, J. (1999). Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogensfindings of the Alexander Project 1992–1996. Journal of Chemotherapy 11, Suppl. 1, 5–21.
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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, 233–9.
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, 87–91.[Web of Science][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, 802–5.
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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, 633–9.
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 Aerobically—Fifth 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
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