JAC Advance Access originally published online on December 19, 2007
Journal of Antimicrobial Chemotherapy 2008 61(2):460-461; doi:10.1093/jac/dkm488
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Research letters |
In vitro activity of ceftobiprole against Burkholderia pseudomallei
Division of Infectious Disease and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
* Corresponding author. Tel/Fax: +66-2-412-5994; E-mail: sivth{at}mahidol.ac.th
Keywords: B. pseudomallei , melioidosis , cephalosporins
Burkholderia pseudomallei, a Gram-negative bacterium, causes a disease called melioidosis in humans and animals.1 The bacterium is a soil organism found mainly in Southeast Asia and Northern Australia. Antibiotics currently recommended for therapy of melioidosis are ceftazidime, imipenem, meropenem, amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, doxycycline and chloramphenicol.1 A development of resistance of B. pseudomallei to the aforementioned antibiotics has been recognized;2,3 hence, a search for new agents effective against B. pseudomallei is needed.
Ceftobiprole is a novel parenteral cephalosporin whose broad spectrum of activity includes most clinically important Gram-positive and Gram-negative bacteria.4
One hundred and fifteen strains of ceftazidime-susceptible B. pseudomallei from different infected patients were selected from our collection. All strains were identified as B. pseudomallei by API 20NE (bioMérieux, France). In vitro susceptibility was determined by Kirby-Bauer disc diffusion for all 115 strains and Etest for 5 randomly chosen strains. Paper discs containing 30 µg ceftobiprole per disc (MASTDISC) and Etest strips of ceftobiprole at concentrations of 0.016–256 mg/L were provided by Janssen-Cilag (Thailand). The disc diffusion test was repeated for six strains of B. pseudomallei in order to determine the reproducibility of the test. The methodology for susceptibility testing was performed by direct colony suspension according to guidelines suggested by the CLSI.5 Quality control was performed by testing susceptibility of Pseudomonas aeruginosa ATCC 27853. The proposed breakpoints for inhibition zone diameters of ceftobiprole are 
20 mm for susceptible, 17–19 mm for intermediate and 
16 mm for resistant. The proposed breakpoints for MICs of ceftobiprole are 4 mg/L for susceptible, 8 mg/L for intermediate and 16 mg/L for resistant.
The inhibition zone diameter of ceftobiprole against P. aeruginosa ATCC 27853 was within the reference limits. The distribution of inhibition zone diameters of ceftobiprole against B. pseudomallei is shown in Table 1. Inhibition zone diameters of 20, 17–19 and 16 mm were observed in 46 (40%), 55 (47.8%) and 14 (12.2%) strains, respectively. Four strains of B. pseudomallei with inhibition zone diameters of 15–19 mm on the initial disc diffusion test had identical inhibition zone diameters on the second test. Another two strains with an inhibition zone diameter of >20 mm had 1 mm difference in inhibition zone diameter on the second test, but the inhibition zone diameters from both tests were still within susceptible values. Four B. pseudomallei strains with an inhibition zone diameter of 17–19 mm had MICs of ceftobiprole of 6–8 mg/L, whereas a strain with an inhibition zone diameter of 16 mm had an MIC of 16 mg/L.
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Our findings indicate that the in vitro activity of ceftobiprole against B. pseudomallei determined by Kirby-Bauer disc diffusion is reproducible and correlates with that determined by Etest. Ceftobiprole has less in vitro activity than ceftazidime against B. pseudomallei, and only 40% of B. pseudomallei strains are susceptible to ceftobiprole.
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Funding |
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 Top Funding Transparency declarationsReferences |
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V. T. is a recipient of Senior Researcher Scholar of the Thailand Research Fund. Janssen-Cilag (Thailand) provided ceftobiprole susceptibility discs and Etest strips for this study.
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Transparency declarations |
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TopFundingTransparency declarationsReferences |
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None to declare.
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Acknowledgements |
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We thank Janssen-Cilag (Thailand) and The Thailand Research Fund for supporting the study.
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References |
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TopFundingTransparency declarationsReferences |
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1 White NJ. Melioidosis. Lancet (2003) 361:1715–22.[CrossRef][Web of Science][Medline]
2
Dance DA, Wuthiekanun V, Chaowagul W, et al. Development of resistance to ceftazidime and co-amoxiclav in Pseudomonas pseudomallei. J Antimicrob Chemother (1991) 28:321–4.
3
Wuthiekanun V, Cheng AC, Chierakul W, et al. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei. J Antimicrob Chemother (2005) 55:1029–31.
4
Jones RN, Deshpande LM, Mutnick AH, et al. In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci. J Antimicrob Chemother (2002) 50:915–32.
5 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing—Fifteenth Informational Supplement M100-S15 (2005) Wayne, PA, USA: CLSI.
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