Journal of Antimicrobial Chemotherapy (2001) 48, 279-281
© 2001 The British Society for Antimicrobial Chemotherapy
Brief report |
In vitro activity of cefditoren against clinical isolates of penicillin-susceptible and penicillin-intermediate strains of Streptococcus pneumoniae isolated in Germany, 1992–1998
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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This study investigates the susceptibility to cefditoren of penicillin-susceptible strains of invasive Streptococcus pneumoniae (n = 312) and of penicillin-intermediate strains of S. pneumoniae (n = 30) isolated mainly from patients with respiratory tract infections. The MIC90s of penicillin-susceptible and -intermediate isolates were as follows: cefditoren,
0.06 and 1 mg/L; penicillin G, 0.06 and 0.5 mg/L. Cefditoren showed the highest activity against the penicillin-intermediate strains investigated compared with the other ß-lactam antibiotics and is therefore considered to be a promising agent for the treatment of infections caused by pneumococci with reduced penicillin susceptibility. |
Introduction |
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Streptococcus pneumoniae is a common cause of serious and life-threatening infections worldwide. The incidence of infections caused by pneumococci resistant to penicillin G and by multiply resistant strains has increased at an alarming rate during the past two decades.1 In contrast, studies carried out in Germany showed lower resistance rates (combined rate of intermediate and resistant strains) among invasive pneumococci, and only a slight increase from 3.8% to 5.4% (MIC
0.12 mg/L) was noted in the period between 1992 and 1999.2 Similar results were obtained in studies focusing on pneumococcal respiratory tract isolates.3 Nevertheless, S. pneumoniae isolates with reduced susceptibility to penicillin, including strains with MICs 2 mg/L and causing therapeutic problems in a few cases, have been reported from Germany.4 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 Mueller–Hinton agar (Oxoid, Basingstoke, UK) was supplemented with 5% sheep blood. An overnight inoculum was suspended in Mueller–Hinton 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 5–7% CO2 for 20–24 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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Erythromycin and tetracycline were less active against penicillin-intermediate pneumococcal isolates (erythromycin MIC90, 8 mg/L; tetracycline MIC90,
64 mg/L) as compared with penicillin-susceptible isolates (erythromycin MIC90, 0.25 mg/L; tetracycline MIC90, 8 mg/L). 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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Corresponding author. Tel: +49-241-8088409; Fax: +49-241-8888483; E-mail: Reinert{at}rwth-aachen.de
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References |
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TopAbstractIntroductionReferences |
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1 . Appelbaum, P. C. (1987). World-wide development of antibiotic resistance in pneumococci. European Journal of Clinical Microbiology 6, 367–77.[Web of Science][Medline]
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, 1398–401.[Web of Science][Medline]
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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, 803–6.
7 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
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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, 3296–9.
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, 265–9.[Web of Science][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, 573–8.[Web of Science][Medline]
Received 1 November 2000; returned 10 April 2001; revised 26 April 2001; accepted 3 May 2001
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