NIH Research Festival
Background: M. abscessus is the second most common nontuberculous mycobacterial species associated with lung disease, and has high levels of antibiotic resistance and poor treatment outcomes. We described changes in clarithromycin and amikacin resistance among patients with serial M. abscessus isolates and their relationship to antibiotic treatment and clinical, radiographic, and microbiological measures. Methods: Patients with amikacin exposure and greater than 50 months duration between M. abscessus isolates were identified. Antimicrobial susceptibility testing was performed by broth microdilution according to CLSI guidelines and PCR and sequencing were performed to identify genetic markers of resistance. Clinical, microbiologic, radiographic, and antibiotic treatment data were abstracted from medical records. Results: Sixteen patients were identified with a median amikacin exposure of 923 days (range: 203-3132). Fifteen patients also received macrolides (median: 2637 days, range: 455-3900). All initial isolates were resistant to clarithromycin (MIC=8). Two patients had later susceptible isolates, which were of a different subspecies (M. abscessus s.s. massiliense) than the initial isolates (M. abscessus s.s. abscessus). All initial isolates were susceptible or intermediate to amikacin, and only one patient had a resistant final isolate (MIC>64), accompanied by an A->G mutation at position 1408 of the 16s rRNA. Between isolates, this patient received 695 days of amikacin treatment. FEV1 decreased significantly over the study period, while C-reactive protein, smear quantity, and the proportion of cavitary disease all significantly increased. Conclusions: These results suggest that amikacin resistance did not develop in this patient population despite intense amikacin exposure, but patients’ disease did continue to progress.
Scientific Focus Area: Microbiology and Infectious Diseases
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