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Original research
Lefamulin for Mycoplasma genitalium treatment failure in Australia and the USA: a case series and pilot open-label parallel arm randomised trial
  1. Meena S Ramchandani1,
  2. Erica L Plummer2,3,
  3. Anika Parker4,
  4. Lenka A Vodstrcil2,3,5,
  5. Olusegun O Soge1,6,
  6. Ivette Aguirre3,
  7. Joong Kim7,
  8. James P Hughes8,
  9. Lindley A Barbee1,
  10. Jørgen Skov Jensen9,
  11. Lisa E Manhart4,
  12. Catriona S Bradshaw2,3,5
  1. 1Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington, USA
  2. 2School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
  3. 3Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia
  4. 4Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
  5. 5Melbourne School Of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
  6. 6Global Health & Medicine, University of Washington Schools of Medicine and Public Health, Seattle, Washington, USA
  7. 7Harborview Investigational Drug Service, University of Washington, Seattle, Washington, USA
  8. 8Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, USA
  9. 9Statens Serum Institut, Copenhagen, Denmark
  1. Correspondence to Dr Catriona S Bradshaw; catriona.bradshaw{at}monash.edu; Dr Lisa E Manhart; lmanhart{at}uw.edu

Abstract

Objectives Mycoplasma genitalium (MG) causes urethritis and is associated with cervicitis, pelvic inflammatory disease and preterm delivery. Antimicrobial resistance is widespread and cure rates are declining. Lefamulin, a novel pleuromutilin, may be effective in cases of treatment failure.

Methods Under compassionate access in Australia and a pilot open-label parallel arm randomised clinical trial in the USA, patients with urogenital MG infection and microbiological treatment failure or contraindications to moxifloxacin were treated with lefamulin monotherapy (600 mg orally two times per for 7 days) or sequential doxycycline-lefamulin (doxycycline 100 mg orally two times per day for 7 days followed by lefamulin for 7 days) (1:1 randomisation in the USA). Two additional regimens were also evaluated in Australia: combination therapy with doxycycline plus lefamulin for 7 days and extended lefamulin therapy with doxycycline for 7 days followed by lefamulin for 14 days. Microbiological cure (negative MG NAAT) was assessed 21–35 days after completing lefamulin. Sustained cure was assessed 42–49 days after treatment.

Results Seventeen heavily pretreated Australian (seen between October 2020 and December 2023) and 11 US cases (recruited between April 2022 and February 2023; 5 randomised to lefamulin monotherapy, 6 randomised to sequential doxycycline-lefamulin) received lefamulin-containing regimens. Sequential doxycycline-lefamulin demonstrated microbiological cure 21–35 days post-treatment in 6 of 12 (50%) Australian and US patients. Three of five (60%) US patients but none of five (0%) Australian patients were cured with lefamulin monotherapy. Combination therapy with doxycycline and lefamulin was ineffective (n=0/2), but extended lefamulin therapy cured two of three (67%). Gastrointestinal side effects occurred in 77% (Australia) and 91% (USA).

Conclusion While cure rates were low, lefamulin was effective in some individuals with MG treatment failure. Additional antibacterial agents for multidrug-resistant infections are needed.

  • mycoplasma genitalium
  • urethritis
  • sexual health
  • bacterial infections
  • drug resistance, bacterial

Data availability statement

Data are available upon reasonable request. Data available on request to CSB and LM.

https://doi.org/10.1136/sextrans-2024-056338

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    Data availability statement

    Data are available upon reasonable request. Data available on request to CSB and LM.

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    Footnotes

    • MSR and ELP are joint first authors.

    • LEM and CSB are joint senior authors.

    • Handling editor Claudia S Estcourt

    • X @lenkavod

    • MSR and ELP contributed equally.

    • LEM and CSB contributed equally.

    • Contributors CSB, JSJ and LEM conceived and designed the study with contributions from LAB and JPH. CSB, MSR and LAB oversaw the clinical care of patients. ELP, LAV and AP coordinated activity with study participants and analysed study data. OOS performed laboratory testing. IA and JK served as pharmacists of record. JPH provided statistical oversight. ELP and MSR led the writing and all authors contributed to the final manuscript. CSB and LEM are responsible for the overall content as guarantor and controlled the decision to publish.

    • Funding Nabriva Therapeutics provided study drug to both sites. The US study was supported by an investigator-initiated research grant from Nabriva Therapeutics, Ltd. to LEM. CSB funded the Australian study and investigators from a National Health and Medical Research Council Investigator Grant (APP 1173361).

    • Competing interests LM has received research funding from Hologic, Inc. and Nabriva Therapeutics, Ltd., consulting fees from Health Advances, and speaker’s fees from MedConnect. CSB has received diagnostic kits for Mycoplasma genitalium testing from Speedx Pty Ltd and Cepheid Pty Ltd but not for this study. JSJ has received grants, speaker’s fee and non-financial support from Hologic, speaker’s fees from LeoPharma and grants from Nabriva, all outside the submitted work, and serves on the scientific advisory board of Roche Molecular Systems, Abbott Molecular, BioMerieux and Cepheid. LAB received funding from Nabriva Therapeutics, Ltd for this study. LAB and OOS received research support, unrelated to this study, from Hologic, Inc, and SpeeDx Pty Ltd. For the rest of the authors, no conflicts of interest were declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.