Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Non-tuberculous mycobacteria in cystic fibrosis lung disease

  Respiratory clinicians across Australia have watched non-tuberculous mycobacteria shift from niche curiosity to frontline concern in cystic fibrosis care over the past two decades. Found in soil, dust and water, these organisms increasingly colonise airways already struggling with thick secretions and chronic inflammation, sometimes sitting quietly for years before accelerating decline.

  People with cystic fibrosis produce dehydrated mucus that traps bacteria. Once a mycobacterium reaches the lower airways, it exploits damaged epithelium, embeds in biofilms and becomes hard to shift. Repeated antibiotic courses add selection pressure, favouring resistant strains.

  In Australia, where around 3,800 people live with cystic fibrosis, climate, an ageing cohort and broader immunosuppressant use have pushed non-tuberculous mycobacterial disease onto every multidisciplinary team agenda. Tropical humidity, inland dust storms and ageing plumbing in older Melbourne and Adelaide homes all shape exposure risk.

  This review covers the organisms, diagnosis, treatment realities and emerging therapies for respiratory physicians, registrars, infectious diseases specialists and allied health colleagues.

  The organisms that matter most

  Two species dominate: Mycobacterium abscessus complex and Mycobacterium avium complex. M. abscessus is more aggressive, notorious for rapid progression, intrinsic resistance and cavitary disease. M. avium complex, including M. intracellulare and M. chimaera, behaves more indolently but appears more often in adult CF sputum.

  Australian Mycobacterium Reference Laboratory data suggest M. abscessus accounts for roughly one in three NTM isolates from CF sputum, with M. avium complex making up most of the remainder. Less common species occasionally appear and create uncertainty about clinical significance.

  Distinguishing simple colonisation from active pulmonary disease remains one of respiratory medicine's trickiest calls. ATS/IDSA criteria, refined with Australian input, are widely used, but applying them rigidly can under-treat young adults with subtle but progressive radiological change.

  Where the bugs come from

  These mycobacteria live in potting mix, showerheads, hot tubs and unchlorinated water. Australians face many exposure opportunities — a Perth vegie patch, a long shower after the beach or a regional motel spa all represent plausible acquisition events. The organism is inhaled or aspirated and, once established, can persist for years.

  Older housing stock creates particular risk, with warm pipes and biofilm-rich tanks acting as reservoirs. Australian whole-genome sequencing studies have matched patient isolates to home bathroom samples, suggesting the household rather than the hospital is often the source. Rural patients drawing untreated bore water along the Murray corridor face higher loads again.

  Bushfire smoke during the Black Summer of 2019–2020 altered respiratory illness patterns across eastern Australia, and teams noted a temporary rise in NTM-positive cultures in the months that followed.

  Diagnosis in everyday practice

  Sputum culture remains the cornerstone, but a single negative sample means little. Most Australian CF centres send three early-morning specimens on separate days when NTM is suspected, and track sputum every three to six months in patients who have ever grown the organism. Solid and liquid media are used together because some species grow poorly on a single platform.

  High-resolution CT complements microbiology by showing the small nodules, tree-in-bud change and cylindrical bronchiectasis that suggest active disease. Molecular probes, MALDI-TOF and targeted PCR panels have shortened identification from weeks to days, allowing earlier treatment decisions.

  Patients often ask whether a positive culture means treatment is needed immediately. The answer depends on symptoms, radiology, bacterial load and trajectory. Many teams adopt a watch-and-wait approach for low-grade M. avium colonisation while acting decisively when M. abscessus is identified, since it rarely stays quiescent long.

  Treatment realities

  M. abscessus lung disease is usually treated with an intensive phase of intravenous amikacin plus a β-lactam such as imipenem or cefoxitin, paired with a macrolide, then months of oral and inhaled continuation therapy. M. avium complex is generally managed with a three-drug oral regimen of macrolide, ethambutol and rifamycin. Courses routinely extend beyond twelve months.

  Side effects range from nausea, taste disturbance and the tinnitus some patients describe as "having the cricket soundtrack on repeat" through to hearing loss and hepatic injury. Audiology services monitor cochlear function during amikacin therapy, and patients on long-term macrolides have ECG surveillance for QT prolongation.

  Adherence is the quiet battle. Daily inhaled antibiotics, fortnightly infusions via portacath and a strict pill schedule take their toll. Nurses at major centres become the patient's main contact, navigating Pharmaceutical Benefits Scheme scripts and home delivery through hospital-in-the-home services.

  CFTR modulators and shifting risk

  The arrival of elexacaftor-tezacaftor-ivacaftor has reshaped the landscape. Improved mucus clearance and reduced inflammation appear to lower acquisition risk in adolescents and young adults, while the impact on established infection is less predictable. Some centres report patients who, after starting modulator therapy, spontaneously cleared previously persistent M. avium from their sputum.

  Drug interactions add another layer. Several NTM antibiotics, including rifamycins and some macrolides, induce or inhibit cytochrome enzymes that modulate modulator metabolism. Dose adjustments are sometimes required, and pharmacists embedded in CF clinics play a central role in keeping regimens safe. Transplant teams across Sydney, Melbourne and Perth now factor modulator response into decision-making, with growing evidence that well-controlled disease improves post-transplant outcomes.

  Lung transplant considerations

  Lung transplantation is the destination for a growing group of Australian CF patients, and NTM status shapes the journey. A history of M. abscessus disease has historically been a relative contraindication, although practice has shifted as eradication strategies have improved.

  Pre-transplant work-up now includes repeat sputum cultures, high-resolution CT and, where indicated, bronchoscopy. Patients with persistent M. abscessus are offered extended targeted therapy before listing, coordinated across transplant, infectious diseases and the referring CF service, which may sit hours from the metro centre.

  After transplant, risks include surgical-site infection, disseminated disease and graft dysfunction related to mycobacterial infection. Prophylaxis regimens vary, lifelong vigilance for recurrence is standard, and CFTR modulators are increasingly continued through the transplant period with pharmacist input to manage interactions with immunosuppressants.

  What Australian data show

  The Australian Cystic Fibrosis Data Registry has tracked NTM prevalence for over a decade. Age-adjusted isolation rates climbed steadily through the 2010s before plateauing at around 13 to 15 percent of adults cultured at any given time, with M. abscessus stable at roughly 3 to 4 percent.

  Research groups at Telethon Kids Institute, the University of Queensland Child Health Research Centre and Melbourne-based collaborators have published work on environmental reservoirs, biofilm biology and the genetic susceptibility markers that may explain why some patients repeatedly grow NTM while siblings with identical CFTR mutations do not.

  Multidisciplinary NTM clinics, modelled on cancer MDTs, now operate at several tertiary centres, bringing together respiratory physicians, infectious diseases specialists, microbiologists, pharmacists and nurses in one visit. These findings are increasingly cited at international meetings, including APSR-affiliated congresses.

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  For clinicians working outside specialist CF centres, the practical takeaway is straightforward: send multiple sputum samples rather than relying on one, involve infectious diseases colleagues early when M. abscessus is identified, and build relationships with the nearest tertiary CF service. Coordinated, persistent care remains the single biggest determinant of outcome in this slowly evolving but stubbornly persistent group of infections.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)