Meropenem-resistant Burkholderia pseudomallei: a concerning single case in Australia with no prior meropenem exposure

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Abstract

We report a case of cutaneous melioidosis in a 54-year-old male with a meropenem-resistant sub-population. He was empirically treated with episodic doxycycline and trimethoprim–sulfamethoxazole; however, the abscess re-accumulated. The patient had no prior exposure to meropenem. A sub-population of the isolate was meropenem resistant with an MIC >32 µg ml −1 and the identification was re-confirmed as Burkholderia pseudomallei . Whole-genome sequencing with ARDaP analysis only revealed a resistance determinant to doxycycline and did not reveal a resistance determinant to meropenem. Furthermore, no carbapenemases were detected through multiple bioinformatics tools. To date, this is the first reported case in Australia of a B. pseudomallei isolate resistant to meropenem without previous carbapenem exposure.

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  1. I believe the additional methodology details describing the repeat testing to confirm original findings lessens the likelihood that the described phenotype arose in vitro during testing. Additionally the authors have added the caveat that in vitro development of resistance during the E-test procedure cannot be fully ruled out. Minor edits Line 197- in vivo should be in vitro The data summary needs to be changed to signpost the available sequencing data of the resistant isolate.

  2. Please address all reviewers comments and make amendments where required, including uploading the genome sequence data generated as part of this study into a publicly accessible repository.

  3. Comments to Author

    The study reports an isolate of B. pseudomallei resistant to meropenem from a patient in Australia. It is interesting to observe the development of MEM resistance of B. pseudomallei in a patient. However, I wish to see this study have shown the comparison WGS data of MEM susceptible and resistance isolates. Many sentences in this manuscript need more clarification and explanation. Line 23: What is ARDaP analysis? What is a resistance determinant to DOX? Line 25: What is the Abricate program? What are in CARD and ResFinder databases? Line 36: It would be appropriate to cite data from a recent large study in Thailand for the mortality rate and readmission. See the following information from Abstract of Chantratital et al, Lancet Reg Health Southeast Asia 2023. Findings—2574 individuals hospitalised …

  4. Comments to Author

    The authors present an interesting melioidosis case study where they identified an isolate with high-level meropenem resistance. The work is well-written and overall, the study is reasonably well conducted. I do, however, have several major reservations with this study and think there are several critical points that need to be addressed. Major comments: Have the authors considered the possibility that the meropenem resistant strain may have evolved in-vitro, and only identified during the Etest procedure? Without the investigation of this possibility, the major conclusions of this manuscript are not well supported by the data. Given the brief description of the methodology, I was unable to determine if this possibility had been investigated. 1) Was a colony purification step undertaken prior to …