A 7-year-old
cystic fibrosis patient with increased
cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with
clarithromycin resistant
Mycobacterium abscessus infection. Treatment was initiated with
clofazimine,
linezolid and
cefoxitin; she responded well to
therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew
clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical
element of clinical information, as the isolation of a genetically distinct organism would have indicated a new
infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the
therapy plan to a goal of 24 months.
Reinfection and relapse are great challenges in patients with
cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have
persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate
re-infection from relapse thus solving this conundrum.