JAC Advance Access originally published online on March 3, 2008
Journal of Antimicrobial Chemotherapy 2008 61(5):1180-1181; doi:10.1093/jac/dkn083
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Research letters |
Antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis isolates in eight Central, East and Baltic European countries in 2005–06: results of the Cefditoren Surveillance Study
1 Department of Medical Microbiology and Antimicrobial Chemotherapy, Fundación Jiménez Díaz, Avenida de Reyes Católicos 2, 28040 Madrid, Spain 2 Scientific Department, Tedec-Meiji Farma, S.A., Madrid, Spain 3 Granadata, Madrid, Spain
* Corresponding author. Tel: +34-915447387; Fax: +34-915494764; E-mail: fsoriano{at}fjd.es
Keywords: ampicillin resistance , amoxicillin/clavulanic acid , cefditoren , β-lactamases
Cefditoren pivoxil is an aminothiazolyl oral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative pathogens and is stable to hydrolysis by many common β-lactamases.1 It has been shown to be active in vitro against many respiratory tract pathogens including Haemophilus influenzae and Moraxella catarrhalis.1 Resistance of both organisms to β-lactam antibiotics is generally conferred by either the presence of β-lactamase or as a result of alterations in penicillin-binding protein 3.
In this study, we compare the in vitro activity of cefditoren with that of nine other antibiotics against 665 and 133 clinical isolates of H. influenzae and M. catarrhalis strains collected from eight Central, East and Baltic European countries. The isolates were prospectively collected from 1 November 2005 to 31 December 2006, in 25 centres from the Czech Republic, Hungary, Poland, Romania, Slovakia, Estonia, Latvia and Lithuania. Isolates from Estonia, Latvia and Lithuania were analysed all together as ‘Baltic countries’. No isolates of M. catarrhalis were received from Romania. Strain isolates were from patients with upper (ear and sinus exudates) and lower (sputum, bronchial washes and bronchial aspirates) respiratory tract infections and bacteraemia. Duplicate isolates from the same patient were not accepted. The identity of the isolates was confirmed by morphology of the colonies, growth on blood and chocolate agar, and API-NH (bioMérieux, Marcy l'Étoile, France).
The following data were collected for each isolate: age group (adults/children), sex, status (outpatients/inpatients) and sample origin (upper respiratory tract/lower respiratory tract/blood).
Susceptibility testing was carried out by the CLSI broth microdilution method, using dried commercial plates (Sensititre, Trek Diagnostic Systems Ltd, West Sussex, UK) reconstituted with Haemophilus test medium for H. influenzae and cation-adjusted Mueller–Hinton broth for M. catarrhalis. The antimicrobials tested were ampicillin, amoxicillin, amoxicillin/clavulanic acid, cefditoren, cefixime, cefpodoxime, cefuroxime, cefotaxime, clarithromycin and levofloxacin. Breakpoint concentrations published by the CLSI (document M100-S16, 2006) to interpret MIC data qualitatively for H. influenzae were also applied to M. catarrhalis. β-Lactamase production was determined using the chromogenic cephalosporin CefinaseTM test (bioMérieux).
The results of the susceptibility testing of H. influenzae isolates are shown in Table 1. Of the 665 isolates tested, 7 (1.1%) were intermediate and 62 (9.3%) resistant to ampicillin. Among ampicillin-resistant isolates, 95.2% were β-lactamase producers. Susceptibility to ampicillin was higher in isolates from the Czech Republic, Slovakia, Hungary, Poland and Baltic countries and lower in those from Romania, the difference being statistically significant (P 
0.005) when compared with any of the other countries. Three (4.8%) ampicillin-resistant isolates were categorized as β-lactamase-negative, ampicillin-resistant (BLNAR); all of them having an MIC of 4 mg/L. No isolate was β-lactamase-positive, amoxicillin/clavulanic-resistant (BLPACR). All isolates were susceptible to amoxicillin/clavulanic acid, cefixime, cefpodoxime, cefuroxime, cefotaxime and levofloxacin. All H. influenzae isolates were inhibited by 0.06 mg/L cefditoren. More than 98% of the isolates were susceptible to clarithromycin and none was categorized as intermediate. No differences in susceptibility to the antibiotics tested were found comparing source, localization of the patient, age or gender.
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One hundred and twenty-seven of the 133 (95.5%) M. catarrhalis isolates produced β-lactamase, but only 94 (70.7%) were non-susceptible to ampicillin using CLSI breakpoints. Susceptibility to ampicillin was higher in isolates from Poland than from any other country, but the difference was not statistically significant. All isolates were susceptible to amoxicillin/clavulanic acid, cefixime, cefpodoxime, cefuroxime, cefotaxime, clarithromycin and levofloxacin. All M. catarrhalis isolates were inhibited by 0.5 mg/L cefditoren and the MIC50/MIC90 values were 0.12/0.5 mg/L. No differences in susceptibility to the antibiotics tested were found comparing source, localization of the patient, age or gender.
The prevalence of H. influenzae isolates producing β-lactamase in Europe varies from low (<6%) in Germany, The Netherlands and Italy to high (>20%) in the UK, Spain and France.2–4 Reports on surveillance studies in our screened countries are scarce but give the following results: 7.9% to 13% in the Czech Republic,3 4.8% to 6.5% in Slovakia,3 0% to 3.3% in Hungary,2,3 6% to 24% in Poland2–5 and 3.0% in Estonia.6 Data on the prevalence of BLNAR H. influenzae isolates are variable but prevalence is usually low (<10%),2–4 although some reports have given figures of up to 20% in Poland.4 No BLPACR isolates were detected in the present study, and the prevalence of such organisms being very low.
A high rate (95.5%) of β-lactamase-producing M. catarrhalis isolates was found in our study, with no significant differences among the screened countries, ampicillin being active only against 29.3% (range, 15.8% to 42.9%) of all isolates (β-lactamase-positive and -negative). Amoxicillin/clavulanic acid, most cephalosporins, clarithromycin, azithromycin and levofloxacin were uniformly active against this organism as reported by others, and cefditoren inhibited all isolates by a concentration of 0.5 mg/L in agreement with that which has been previously reported.1
In summary, this study confirms and completes information on antimicrobial susceptibility of H. influenzae and M. catarrhalis in some Central, East and Baltic European countries and demonstrated the relevant in vitro activity of cefditoren against both H. influenzae and M. catarrhalis independently of the resistance phenotype, all isolates being inhibited by concentrations of 0.06 and 0.5 mg/L, respectively.
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Funding |
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 Top Funding Transparency declarationsReferences |
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This study was funded by a grant from Tedec-Meiji Farma, S.A., Madrid, Spain.
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Transparency declarations |
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TopFundingTransparency declarationsReferences |
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P. C. and M. G. are scientific members of Tedec-Meiji Farma, S.A. All other authors have none to declare.
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Acknowledgements |
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The contributions of the following investigators are acknowledged. Czech Republic: P. Urbaskova, T. Bergerova, E. Bendova, M. Hornikova, E. Chmelarova and V. Jindrak; Hungary: F. Lakatos, K. Szarka, L. Szikra, M. Konkoly-Thege and E. Nagy; Poland: W. Hryneiewicz; Romania: M. Pana, M. Andrei, D. Leu, E. Farkas, L. Vasile and D. Tudorache; Slovakia: J. Trupl, M. Niks and H. Hupkova; Estonia: P. Naaber; Latvia: A. Balode; Lithuania: J. Miciuleviciene and G. Sinkute.
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References |
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TopFundingTransparency declarationsReferences |
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1 Wellington K, Curran MP. Cefditoren pivoxil. A review of its use in the treatment of bacterial infections. Drugs (2004) 64:2597–618.[CrossRef][Web of Science][Medline]
2 Hoban D, Felmingham D. The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections. J Antimicrob Chemother (2002) 50(Suppl_S1):49–59.[Abstract]
3
Felmingham D, Grüneberg RN. The Alexander Project 1996–1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections. J Antimicrob Chemother (2000) 45:191–203.
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Fluit AC, Florijn A, Verhoef J, et al. Susceptibility of European β-lactamase-positive and -negative Haemophilus influenzae isolates from the periods 1997/1998 and 2002/2003. J Antimicrob Chemother (2005) 56:133–8.
5 Semczuk K, Dzierzanowska-Fangrat K, Lopaciuk U, et al. Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae isolated from children with community-acquired respiratory tract infections in Central Poland. Int J Antimicrob Agents (2004) 23:39–43.[CrossRef][Web of Science][Medline]
6 Altraja J, Naaber P, Tamm E, et al. Antimicrobial susceptibility of common pathogens from community-acquired lower respiratory tract infections in Estonia. J Chemother (2006) 18:603–9.[Web of Science][Medline]
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