Institute of Medical Microbiology and National Reference Center for Streptococci, University Hospital (RWTH) Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany
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Abstract |
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Introduction |
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Cefditoren (ME 1206) is a methoxyiminocephem of the so-called third generation cephalosporin class, which, when formulated as a pivoxil ester, has acceptable bioavailability for oral use.5
In the present study, isolates were collected by 60 medical centres as part of ongoing nationwide surveillance studies conducted by the National Reference Center for Streptococci in Germany between 1992 and 1998. Identification of pneumococcus was confirmed by optochin susceptibility and bile solubility. Isolates were stored at 70°C (Microbank, Mast Diagnostics, Reinfeld, Germany) and were subcultured twice before testing. A total of 342 strains were included in this study: 312 penicillin-susceptible strains (MICs 0.06 mg/L) collected from blood cultures of patients with bacteraemic pneumococcal pneumonia and 30 penicillin-intermediate strains isolated mainly from patients with respiratory tract infections. Agar dilution was performed as described previously6 using the NCCLS breakpoints.7 MuellerHinton agar (Oxoid, Basingstoke, UK) was supplemented with 5% sheep blood. An overnight inoculum was suspended in MuellerHinton broth (Difco, Detroit, MI, USA) to a turbidity of 0.5 McFarland standard and the final inoculum contained 104 pneumococcal cells. Plates were then incubated at 35°C with 57% CO2 for 2024 h. The pneumococcal reference strain ATCC 49619 was used as a control. Results of susceptibility testing are presented in the Table
. Cefditoren showed good activity against penicillin-susceptible (MIC50,
0.06 mg/L; MIC90,
0.06 mg/L) and penicillin-intermediate (MIC50, 0.125 mg/L; MIC90, 1 mg/L) strains. According to the breakpoint concentrations, based upon pharmacokinetic and pharmacodynamic criteria as advocated by Kelly et al.8 [
2 mg/L (susceptible), 4 mg/L (intermediate) and
8 mg/L (resistant)], all strains were found to be susceptible to cefditoren. If the breakpoint of resistance of 1 mg/L by Fuchs et al.9 is applied, four strains are categorized as cefditoren resistant. The MICs of cefditoren for penicillin-intermediate strains were slightly lower than those of penicillin, amoxycillin and cefpodoxime, and significantly lower than those of cefixime and cefuroxime.
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The present study confirmed the excellent activity of cefditoren against penicillin-susceptible and penicillin-intermediate pneumococci. In a study by Jones et al.,10 the comparative in vitro activity of cefditoren for 500 strains of S. pneumoniae was determined, and confirmed a reduction in activity for S. pneumoniae, with elevations in the penicillin MICs. Cefditoren demonstrated the greatest activity of all ß-lactams for penicillin-intermediate (n = 108) isolates (MIC50, 0.12 mg/L; MIC90, 0.5 mg/L), which was confirmed by the present study. As in the present investigation, cefpodoxime and ampicillin also showed reasonable activity against penicillin-intermediate isolates, but cefixime and cefuroxime were less active. Similar results were obtained in other studies.9 In summary, cefditoren appears to be a very promising ß-lactam whose range includes penicillin-intermediate S. pneumoniae.
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Notes |
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References |
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2 . Reinert, R. R., Queck, A., Kaufhold, A., Kresken, M. & Lütticken, R. (1995). Antimicrobial resistance and type distribution of Streptococcus pneumoniae in Germany, 1992. Clinical Infectious Diseases 21, 1398401.[ISI][Medline]
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Reinert, R. R., Simic, S., Al-Lahham, A., Reinert, S., Lemperle, M. & Lütticken, R. (2001). Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients with respiratory tract infections in Germany from 1998 to 1999: results of a national surveillance study. Journal of Clinical Microbiology 39, 11879.
4 . Reinert, R. R., Kaufhold, A. & Kierdorf, H. (1992). Penicillinresistant pneumococcus in community-acquired bacteremic pneumonia in Germany. Infection 20, 2389.[ISI][Medline]
5 . Tamura, A., Okamoto, R., Yoshida, T., Yamamoto, H., Kondo, S., Inoue, M. et al. (1988). In vitro and in vivo antibacterial activities of ME1207, a new oral cephalosporin. Antimicrobial Agents and Chemotherapy 32, 14216.[ISI][Medline]
6 . Reinert, R., Schlaeger, J. & Lütticken, R. (1998). Moxifloxacin: a comparison with other fluoroquinolones of the in-vitro activity against Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy 42, 8036.[Abstract]
7 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
8
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Kelly, L. M., Jacobs, M. R. & Appelbaum, P. C. (1999). Comparison of agar dilution, microdilution, E-test, and disk diffusion methods for testing activity of cefditoren against Streptococcus pneumoniae. Journal of Clinical Microbiology 37, 32969.
9 . Fuchs, P. C., Barry, A. L. & Brown, S. D. (2000). Susceptibility of Streptococcus pneumoniae and Haemophilus influenzae to cefditoren, and provisional interpretive criteria. Diagnostic Microbiology and Infectious Diseases 37, 2659.[ISI][Medline]
10 . Jones, R. N., Biedenbach, D. J., Croco, M. A. & Barrett, M. S. (1998). In vitro evaluation of a novel orally administered cephalosporin (Cefditoren) tested against 1249 recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Diagnostic Microbiology and Infectious Diseases 31, 5738.[ISI][Medline]
Received 1 November 2000; returned 10 April 2001; revised 26 April 2001; accepted 3 May 2001