Activity of five fluoroquinolones against 71 isolates of Burkholderia pseudomallei

P. L. Ho*, Terence K. M. Cheung, R. Kinoshita, Cindy W. S. Tse, K. Y. Yuen and P. Y. Chau

Antimicrobial Resistance Study Group, Centre of Infection, Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong

Sir,

Newer fluoroquinolones have gained popularity for use as monotherapy for community-acquired pneumonia in many parts of the world. This practice deserves caution from clinicians in South East Asia, where melioidosis is endemic and Burkholderia pseudomallei is a major cause of community-acquired pneumonia; in north-east Thailand, 18% of community-acquired bacteraemia is caused by the bacterium. One report states that it is the most common cause of fatal community-acquired bactaeremic pneumonia, with an overall mortality of 21%.1 In Singapore, where the disease is notifiable, it accounts for 4% of severe community-acquired pneumonia, and up to 120 cases are diagnosed annually. In Hong Kong, serological evidence of exposure was found in 14% of patients in a sanatorium.2 In the present study, we examined the in vitro antibacterial activities of the newer fluoroquinolones against isolates of B. pseudomallei collected in Hong Kong and Thailand.

A total of 71 B. pseudomallei isolates was studied. These isolates were obtained from infected animals (36) or humans (18) with the disease, or from environmental sources (17), between 1975 and 2001. Only one isolate from each source was tested. Two isolates from one patient with two episodes of infection 1 year apart were included. The remaining 16 patient isolates were obtained from different subjects. The origins of the 35 animal isolates included: dolphin (13), whale (six), seal (three), penguin (one), sea lion (two), parrot (nine), dove (one) and llama (one). Environmental isolates were obtained either from soil (14) or from typhoon aerosol (three). Except for five human isolates from Thailand, all other isolates were obtained from Hong Kong. All B. pseudomallei isolates were identified by their characteristic colonial morphology on Ashdown medium, a positive oxidase reaction, resistance to polymyxin B and gentamicin, the API 20NE system and a positive reaction to a specific agglutination kit.3 All isolates tested were arabinose negative.

The Etest (AB Biodisk, Solna, Sweden) was used to determine MICs. Tests were carried out on Mueller–Hinton agar (Oxoid, Basingstoke, UK) according to the manufacturer’s instruction. The plates were incubated at 35°C in ambient air for 16–20 h. The following antimicrobial agents were used: co-amoxiclav, piperacillin–tazobactam, cefoperazone–sulbactam, ceftazidime, imipenem, meropenem, ciprofloxacin, gatifloxacin, grepafloxacin, clinafloxacin and moxifloxacin. All MIC results were interpreted according to NCCLS criteria (sensitive, intermediate and resistant, respectively, in mg/L): <=1, 2 and >=4 for ciprofloxacin; and <=2, 4 and >=8 for gatifloxacin.4 No breakpoints were available for moxifloxacin, grepafloxacin and clinafloxacin. Quality control strains (Streptococcus pneumoniae ATCC 49619, Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922) were included with each run.

All isolates were susceptible to the six ß-lactams and ß-lactam–ß-lactamase inhibitor combinations. In descending order of activities, MIC50/MIC90 of the agents were as follows: 0.5/1 mg/L of imipenem, 1/1 mg/L of piperacillin–tazobactam, 1/4 mg/L of meropenem, 2/4 mg/L of ceftazidime, 4/8 mg/L of co-amoxiclav and 8/8 mg/L of cefoperazone–sulbactam. The distribution of MICs of the fluoroquinolones is shown in Figure 1. Clinafloxacin (0.5/1 mg/L) had the lowest MIC50/MIC90, followed by moxifloxacin (2/4 mg/L), ciprofloxacin (2/8 mg/L), grepafloxacin (4/8 mg/L) and gatifloxacin (4/16 mg/L). Overall, 8.5% of 71 isolates were susceptible to ciprofloxacin, 49.3% were intermediate and 42.3% were resistant. For grepafloxacin and gatifloxacin, 15.5% and 21.1%, respectively, were susceptible.



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Figure 1. Distribution of MICs of five fluoroquinolones for 71 isolates of B. pseudomallei. Black bars, clinafloxacin; white bars, ciprofloxacin; grey bars, moxifloxacin; striped bars, gatifloxacin; spotted bars, grepafloxacin.

 
As in our earlier studies,5 the prototype fluoroquinolone, ciprofloxacin, showed only weak in vitro activity against B. pseudomallei. With the exception of clinafloxacin, the other quinolones, including grepafloxacin, gatifloxacin and moxifloxacin, were no more potent than ciprofloxacin. This is consistent with a study from Taiwan, in which the MICs of trovafloxacin and moxifloxacin for 17 B. pseudomallei isolates were reported to be 1–4 mg/L.1 Fluoroquinolones achieve high intracellular concentrations and hence might still be clinically useful for intracellular infection such as melioidosis. Nonetheless, one study found the fluoroquinolones ciprofloxacin or ofloxacin to be inferior to standard therapy (co-amoxiclav or the combination of chloramphenicol, doxycycline and trimethoprim–sulfamethoxazole) for maintenance treatment of melioidosis.6 In summary, the activity of the newer fluoroquinolones, such as gatifloxacin and moxifloxacin against B. pseudomallei is limited. Until more data are available, these agents should not be used alone for empirical therapy of community-acquired pneumonia in areas where the risk of melioidosis is significant.

Acknowledgements

We thank Ocean Park Corporation (Hong Kong) for kindly providing us with 33 B. pseudomallei isolates. This work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (project no. HKU 7282/97M).

Footnotes

* Corresponding author. Tel: +852-2855-4892;Fax: +852-2855-1241; E-mail: plho{at}hkucc.hku.hk Back

References

1 . Hsueh, P. R., Teng, L. J., Lee, L. N., Yu, C. J., Yang, P. C., Ho, S. W. et al. (2001). Melioidosis: an emerging infection in Taiwan? Emerging Infectious Diseases 7, 428–33.[ISI][Medline]

2 . So, S. Y., Chau, P. Y., Aquinas, M., Gabriel, M. & Lam, W. K. (1987). Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 1017–9.[ISI][Medline]

3 . Smith, M. D., Wuthiekanun, V., Walsh, A. L. & Pitt, T. L. (1993). Latex agglutination test for identification of Pseudomonas pseudomallei. Journal of Clinical Pathology 46, 374–5.[Abstract]

4 . National Committee for Clinical Laboratory Standards. (2001). Performance Standards for Antimicrobial Susceptibility Testing: Eleventh Informational Supplement M100-S10. NCCLS, Wayne, PA.

5 . Chau, P. Y., Ng, W. S., Leung, Y. K. & Lolekha, S. (1986). In vitro susceptibility of strains of Pseudomonas pseudomallei isolated in Thailand and Hong Kong to some newer beta-lactam antibiotics and quinolone derivatives. Journal of Infectious Diseases 153, 167–70.[ISI][Medline]

6 . Chaowagul, W., Suputtamongkul, Y., Smith, M. D. & White, N. J. (1997). Oral fluoroquinolones for maintenance treatment of melioidosis. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, 599–601.[ISI][Medline]





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