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Indian Journal of Microbiology

, Volume 58, Issue 2, pp 244–247 | Cite as

In-Vitro Activity of Doxycycline and β-Lactam Combinations Against Different Strains of Burkholderia pseudomallei

  • Nurul Iman Mohamad
  • Azian Harun
  • Habsah Hasan
  • Zakuan Zainy Deris
Short Communication
  • 144 Downloads

Abstract

Although doxycycline is active against Burkholderia pseudomallei and has been used in the eradication stage of melioidosis therapy, it is not regularly used during the initial intensive phase. In order to assess its potential use in intensive phase therapy, we investigated in vitro pharmacodynamic activity of doxycycline and β-lactams alone and in combination against four Malaysian strains of B. pseudomallei. Using a checkerboard assay, the combinations of doxycycline and imipenem, doxycycline and ceftazidime, and doxycycline and amoxicillin–clavulanate tested against four strains showed indifferent effects with summation fractional inhibitory concentration values ranging from 0.62 to 2.12. Time-kill experiments also indicated that the combinations of doxycycline/β-lactam antibiotics against four tested strains did not fulfil synergy criteria, in which all combinations showed indifferent effects with − 1.36 to 1.26-log CFU/mL compared to the most active monotherapy regimen in each combination. No re-growth of bacteria was detected after the early killing in doxycycline/β-lactam combination regimens compared to β-lactam monotherapy regimens, in which 9 out of 10 were associated with re-growth of bacteria. As no synergistic activity was observed, this in vitro study showed that doxycycline offers no additional benefit to be used in combination with β-lactams in the intensive phase of therapy.

Keywords

Melioidosis Burkholderia pseudomallei Doxycycline β-Lactams Drug combination 

Notes

Acknowledgements

This study was supported by USM short term Grant (304.PPSP.61313057). This study was approved by Universiti Sains Malaysia’s Human Ethics Committee (Reference No. Ref: USM/JEPeM/16110493).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Wolf J (2017) Melioidosis: the most neglected tropical disease. American Society for Microbiology. https://www.asm.org/index.php/mbiosphere/item/5883-melioidosis-the-most-neglected-tropical-disease. Accessed 10 Oct 2017
  2. 2.
    Dance DAB (2000) Melioidosis as an emerging global problem. Acta Trop 74:115–119.  https://doi.org/10.1016/S0001-706X(99)00059-5 CrossRefPubMedGoogle Scholar
  3. 3.
    Deris ZZ, Hasan H, Siti Suraiya MN (2010) Clinical characteristics and outcomes of bacteraemic melioidosis in a teaching hospital in a northeastern state of Malaysia: a five-year review. J Infect Dev Ctries 4:430–435.  https://doi.org/10.3855/jidc.491 PubMedGoogle Scholar
  4. 4.
    Dance D (2014) Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents 43:310–318.  https://doi.org/10.1016/j.ijantimicag.2014.01.005 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Malaysian Ministry of Health (2014) National antibiotic guidelines 2014. http://www.pharmacygovmy/v2/en/documents/national-antibiotic-guideline-nag-2nd-editionhtml. Accessed 27 Dec 2016
  6. 6.
    Yazid MB, Fauzi MH, Hasan H, Md Noh AY, Deris ZZ (2017) An 11-year analysis of emergency presentations of melioidosis in Northeastern Malaysia. J Immigr Minor Health 19:774–777.  https://doi.org/10.1007/s10903-016-0429-8 CrossRefPubMedGoogle Scholar
  7. 7.
    Lipsitz R, Garges S, Aurigemma R, Baccam P, Blaney DD, Cheng AC et al (2012) Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei Infection, 2010. Emerg Infect Dis 18:e2.  https://doi.org/10.3201/eid1812.120638 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zueter AM, Rahman ZA, Yean CY, Harun A (2015) Brief communication genotyping of Burkholderia pseudomallei revealed high genetic variability among isolates from a single population group. Int J Mol Epidemiol Genet 6:41–47PubMedPubMedCentralGoogle Scholar
  9. 9.
    Balouiri M, Sadiki M, Ibnsouda SK (2016) Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal 6:71–79.  https://doi.org/10.1016/j.jpha.2015.11.005 CrossRefPubMedGoogle Scholar
  10. 10.
    White RL, Burgess DS, Manduru M, Bosso JA (1996) Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test. Antimicrob Agents Chemother 40:1914–1918PubMedPubMedCentralGoogle Scholar
  11. 11.
    Ankomah P, Johnson PJ, Levin BR (2013) The pharmaco -, population and evolutionary dynamics of multi-drug therapy: experiments with S. aureus and E. coli and computer simulations. PLoS Pathog 9:e1003300.  https://doi.org/10.1371/journal.ppat.1003300 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sivalingam SP, Sim SH, Jasper LC, Wang D, Liu Y, Ooi EE (2008) Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole. J Antimicrob Chemother 61:674–678.  https://doi.org/10.1093/jac/dkm527 CrossRefPubMedGoogle Scholar

Copyright information

© Association of Microbiologists of India 2018

Authors and Affiliations

  1. 1.Department of Medical Microbiology and Parasitology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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