Journal of Antimicrobial Chemotherapy (2001) 47, 722-724
© 2001 The British Society for Antimicrobial Chemotherapy
Correspondence |
In vitro activity of sitafloxacin against Clostridium difficile
a Division of Infectious Diseases and Immunologic Diseases, Department of Internal Medicine, University of California-Davis, Medical Center, PSSB, Suite 500, 4150 V Street, Sacramento, CA 95817, USA; b Institute for Medical Microbiology and Epidemiology of Infectious Diseases, University of Leipzig, Liebigstrasse 24, 04103 Leipzig, Germany; c Department of Pharmaceutical Biology, Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany
Sir,
The development of new fluoroquinolones with enhanced activity against Gram-positive bacteria and anaerobes has given clinicians alternatives for the treatment of severe infections caused by such organisms. Sitafloxacin (DU-6859a) is one of the drugs within the new generation of fluoroquinolones. The compound, together with clinafloxacin, gatifloxacin, gemifloxacin, moxifloxacin and trovafloxacin, constitutes group IV of the fluoroquinolones according to Naber et al.1 Sitafloxacin is designed for once- daily oral administration at a dose of 200 mg, resulting in a mean Cmax of 1.86 mg/L with a reported t
in plasma of 4.6 h.2 Analysis of the post-antibiotic effect (PAE) and the bactericidal activity on multiple drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) supported the adequacy of the dosing regimen.2
Owing to the increased use of fluoroquinolones and the alarming numbers of strains that have developed resistance against this class of antimicrobials, many studies have been undertaken to investigate the epidemiology and mechanisms of resistance of bacteria to fluoroquinolones. The prior use of fluoroquinolones was found to be a major risk factor for the isolation of ciprofloxacin-resistant bacteria.3 A study investigating the in vitro inhibitory activities of sitafloxacin against Streptococcus pneumoniae DNA gyrase and topoisomerase IV found inhibitory activity of this agent against both enzymes, without preference for either of them.4 Since this suggests that the development of sitafloxacin resistance would require mutations in both enzymes, one should expect the incidence of sitafloxacin-resistance to be low.4
In a study testing 8796 clinical isolates, sitafloxacin showed excellent in vitro activity against Gram-positive bacteria, including MRSA (MIC50/90 0.25/0.5 mg/L), and compared with other fluoroquinolones, four times higher activity against Enterococcus faecalis (MIC50/90 0.12/2 mg/L). Sitafloxacin showed at least an equal or slightly better activity than ciprofloxacin against Gram-negative bacteria. Moreover, MICs of sitafloxacin against ciprofloxacin-resistant Enterobacteriaceae were at least three dilution steps lower than those of ciprofloxacin.5 Sitafloxacin also showed good activity against anaerobic bacteria, including Gram-positive bacteria, i.e. clostridia and peptostreptococci.6
In the present study, we analysed the antimicrobial susceptibility of 80 clinical isolates of Clostridium difficile. Nineteen strains that were found to be highly resistant to moxifloxacin (MIC50/90s 
16 mg/L) were then selected for extended antimicrobial susceptibility testing. For these strains, the MICs of norfloxacin, pefloxacin, ciprofloxacin, fleroxacin, ofloxacin, enoxacin, grepafloxacin, sparfloxacin, gatifloxacin, gemifloxacin, trovafloxacin, moxifloxacin, clinafloxacin and sitafloxacin were determined, employing broth microdilution in accordance with the recommendations of the Deutsches Institut für Normung (DIN) standard 58940-83. The distribution of MICs and the MIC50 and MIC90 values for the 19 clinical isolates are summarized in the Table
. All strains were inhibited by 2 mg/L of sitafloxacin (MIC50/90 1/2 mg.L). Only clinafloxacin showed similar activity (MIC50/90 2/2 mg/L), whereas four other group IV fluoroquinolones showed insufficient in vitro activity against the 19 isolates (MIC50/90 values 16/32 mg/L and 32/32 mg/L, respectively).
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The increase in multidrug-resistant bacteria causing nosocomial infections advocates the need for new compounds with high activity against bacteria carrying multiple resistance genes. Testing 73 ciprofloxacin-resistant Enterococcus faecium strains, Brisse et al.7 found 36 isolates to be susceptible to sitafloxacin. The results of the study presented here show a high in vitro activity of sitafloxacin against otherwise fluoroquinolone-resistant C. difficile strains. This is another indication of the increased activity of sitafloxacin against Gram-positive bacteria. Further studies are needed to determine whether this antibiotic agent is also inhibiting both the DNA gyrase and the topoisomerase IV of C. difficile strains. This would pos-sibly explain its activity against otherwise fluoroquinolone-resistant organisms. The data presented here make sitafloxacin a candidate for clinical evaluation of its therapeutic efficacy in C. difficile infection.
In summary, sitafloxacin demonstrated in vitro activity against Gram-positive and -negative bacteria, suggesting an important role for sitafloxacin in the treatment of infections due to MRSA, enterococci and other multidrugresistant bacteria. However, the increased use of this class of antibiotics and the rapid development of resistance challenges the clinicians with choosing the optimal antibiotic treatment. Additionally, these data should encourage the physician to monitor susceptibility patterns carefully.
Acknowledgments
G.A. was supported by a grant from the Paul-Ehrlich-Society, Germany.
Notes
* Corresponding author. Tel: +1-916-734-3741; Fax: +1-916-734-0518; E-mail: grit.ackermann{at}ucdmc.ucdavis.edu 
References
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2 . Giamarellou-Bourgoulis, E. J., Sambatakou, H., Grecka, P., Chryssouli, Z. & Giamarellou, H. (1999). Sitafloxacin (DU-6859a) and trovafloxacin: Postantibiotic effect and in vitro interactions with rifampin on methicillin-resistant Staphylococcus aureus. Diagnostic Microbiology and Infectious Diseases 34, 301–7.[Web of Science][Medline]
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