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

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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.

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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).

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Authors and Affiliations

  1. Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Nurul Iman Mohamad, Azian Harun, Habsah Hasan & Zakuan Zainy Deris

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  1. Nurul Iman Mohamad
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  2. Azian Harun
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  3. Habsah Hasan
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  4. Zakuan Zainy Deris
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Correspondence to Zakuan Zainy Deris.

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All authors declare that they have no conflict of interest.

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All authors meet the ICMJE authorship criteria.

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Mohamad, N.I., Harun, A., Hasan, H. et al. In-Vitro Activity of Doxycycline and β-Lactam Combinations Against Different Strains of Burkholderia pseudomallei. Indian J Microbiol 58, 244–247 (2018). https://doi.org/10.1007/s12088-018-0722-4

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  • DOI: https://doi.org/10.1007/s12088-018-0722-4

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