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• Macrolides and Mycobacterium abscessus - time for a rethink?
  Ross J Langley, Don Urquhart, Stephen Bowhay and Christine Peters
  Published on: 15 March 2018

• Published on: 15 March 2018

  Macrolides and Mycobacterium abscessus - time for a rethink?

  • Ross J Langley, Paediatric Respiratory Registrar Department of Paediatric Respiratory and Sleep Medicine, Royal Hospital for Sick Children, Edinburgh
  • Other Contributors:
    • Don Urquhart, Paediatric Respiratory Consultant
    • Stephen Bowhay, Paediatric Pharmacist
    • Christine Peters, Consultant Microbiologist

  Sir

  We read with interest the latest BTS guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD).1
  Of particular interest was the section relating to the treatment of Mycobacterium abscessus –pulmonary disease. The evidence for the treatment regimes remains poor (Grade D) and within paediatric population the experience of treatment strategies is based on both adult guidelines and clinical expertise. Questions remain about the rationale for the use of macrolides in organisms with inducible resistance. Table 8 in the article recommends the use of oral macrolides during both induction and continuation phase even if inducible macrolide resistance has been demonstrated in vitro. By definition, M. abscessus abscessus strains will possess a functional erm(41) gene, 2 and therefore we feel use of this drug may be inappropriate for this subspecies.

  Azithromycin is a bacteriostatic antibiotic, with intracellular penetration superior to that of the aminoglycosides. 3 M. abscessus complex can thrive within the intracellular environment. 4 Given the exposure of intracellular M. abscessus abscessus to a bacteriostatic agent we suggest this may induce not only resistance but also quiescence within the bacterium and therefore the bactericidal action of aminoglycosides would be significantly impaired given the lack of active protein synthesis. This quiescent state is likely given the difficulty in isolating this organism whilst the...

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  Sir

  We read with interest the latest BTS guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD).1
  Of particular interest was the section relating to the treatment of Mycobacterium abscessus –pulmonary disease. The evidence for the treatment regimes remains poor (Grade D) and within paediatric population the experience of treatment strategies is based on both adult guidelines and clinical expertise. Questions remain about the rationale for the use of macrolides in organisms with inducible resistance. Table 8 in the article recommends the use of oral macrolides during both induction and continuation phase even if inducible macrolide resistance has been demonstrated in vitro. By definition, M. abscessus abscessus strains will possess a functional erm(41) gene, 2 and therefore we feel use of this drug may be inappropriate for this subspecies.

  Azithromycin is a bacteriostatic antibiotic, with intracellular penetration superior to that of the aminoglycosides. 3 M. abscessus complex can thrive within the intracellular environment. 4 Given the exposure of intracellular M. abscessus abscessus to a bacteriostatic agent we suggest this may induce not only resistance but also quiescence within the bacterium and therefore the bactericidal action of aminoglycosides would be significantly impaired given the lack of active protein synthesis. This quiescent state is likely given the difficulty in isolating this organism whilst the patient is exposed to macrolides and explains the recommendation of discontinuing long term macrolide use prior to resampling for M. abscessus abscessus. Furthermore, the use of macrolides for the treatment of other Mycobacterial species (for example M. fortuitum or M. smegmatis) that possess functional erm genes is not recommended. 5 Thus when declaring someone to have cleared M. abscessus when on treatment, can one really be sure that this is not simply an assumption of quiescent state to later rear its’ ugly head? Likewise the declaration of a re-emergence on cessation of treatment may be the head rearing.

  Much of the experience of macrolide use appears historical dating back to the mid 1990s, and their apparent efficacy reflects pre-subspeciating taxonomy where strains may have been identified as M. abscessus but in actual fact could have been M. abscessus massiliense with dysfunctional erm(41) genes and therefore macrolide sensitivity. 2

  Although we welcome a guideline to direct clinical practice, we note that there has been little progress in updating the evidence and this most recent guideline is based on treatment protocols devised almost 25 years ago which do not reflect advances in bacterial taxonomy and genetic analysis of antimicrobial resistance. Work to delineate optimal therapy for M. abscessus complex infections is urgently warranted.

  Ref.
  1. Haworth et al. (2017). Thorax 72: Suppl 2
  2. Bastian et al. (2011). Anti Agen & Chemo 55: 775-781
  3. Carryn et al. (2003). Infect. Dis. Clin. N. Am 17: 615-634
  4. Medjahed et al. (2010). Trend Micro 18: 117-123
  5. Nagh et al. (2005). JAC 55: 170-177

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  Conflict of Interest:
  None declared.

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